bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2024‒08‒25
63 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Neurobiological and anti-aging benefits of yoga: A comprehensive review of recent advances in non-pharmacological therapy.
  2. Advancing Longevity: Exploring Anti-Aging Pharmaceuticals in Contemporary Clinical Trials amidst Aging Dynamics.
  3. Research on the anti-oxidant and anti-aging effects of Polygonatum kingianum saponins in Caenorhabditis elegans.
  4. Damage-Induced Senescent Immune Cells Regulate Regeneration of the Zebrafish Retina.
  5. Oxidative Phosphorylation and Fatty Acid Oxidation in Slow-Aging Mice.
  6. The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.
  7. Resolvin D1 suppresses macrophage senescence and splenic fibrosis in aged mice.
  8. The influential responsibility of sirtuins in senescence and associated diseases: A review.
  9. Consolidating multiple evolutionary theories of ageing suggests a need for new approaches to study genetic contributions to ageing decline.
  10. Investigation of the anti-skin aging effects of taurine through mendelian randomization analysis of its relationship with immune cells.
  11. Aging and physiological barriers: mechanisms of barrier integrity changes and implications for age-related diseases.
  12. Oxidative stress-induced gene expression changes in prostate epithelial cells in vitro reveal a robust signature of normal prostatic senescence and aging.
  13. Novel Thermus thermophilus and Bacillus subtilis mixed-culture ferment extract provides potent skin benefits in vitro and protects skin from aging.
  14. Research progress on interferon and cellular senescence.
  15. The role of phagocytic cells in aging: insights from vertebrate and invertebrate models.
  16. Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway.
  17. The impact of carnosine on biological ageing - A geroscience approach.
  18. Cellular oxidants and the proteostasis network: balance between activation and destruction.
  19. The effect of axenic dietary restriction on the age-related changes in C. elegans.
  20. DNA damage (8-OHdG) and telomere length in captive Psittacidae birds with different longevity.
  21. Short-term post-fast refeeding enhances intestinal stemness via polyamines.
  22. Epidermal stem cells: skin surveillance and clinical perspective.
  23. Targeting multiple hallmarks of mammalian aging with combinations of interventions.
  24. Inflated expectations: the strange craze for translational research on aging : Given existing confusion about the basic science of aging, why the high optimism in the private sector about the prospects of developing anti-aging treatments?
  25. FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species.
  26. Misregulation of mitochondrial 6mA promotes the propagation of mutant mtDNA and causes aging in C. elegans.
  27. DNA synthesis across DNA hairpins by human PrimPol.
  28. Adipose-derived stem cell therapy for spinal cord injuries: Advances, challenges, and future directions.
  29. IGFBP7 mediates oxLDL-induced human vascular endothelial cell injury by suppressing the expression of SIRT1.
  30. RIOK2 transcriptionally regulates TRiC and dyskerin complexes to prevent telomere shortening.
  31. Role of Curcuma longae Rhizoma in medical applications: research challenges and opportunities.
  32. Controllable self-assembly of tyrosine-rich triblock peptides into robust collagen mimetic bioscaffolds for aging skin rejuvenation.
  33. Biosponge-Encased Placental Stem Cells for Volumetric Muscle Loss Repair.
  34. Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice.
  35. On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.
  36. A highly sensitive reporter system to monitor endogenous YAP1/TAZ activity and its application in various human cells.
  37. Cooperative nuclear action of RNA-binding proteins PSF and G3BP2 to sustain neuronal cell viability is decreased in aging and dementia.
  38. FOXM1 affects oxidative stress, mitochondrial function, and the DNA damage response by regulating p21 in aging oocytes.
  39. Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-β-SMAD axis.
  40. Enhanced cellular longevity arising from environmental fluctuations.
  41. Ethanol Extract of Propolis Attenuates Liver Lipid Metabolism Disorder in High-Fat Diet-Fed SAMP8 Mice.
  42. Current developments of gene therapy in human diseases.
  43. Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders.
  44. Adipose-derived stem cells transplantation improves survival and alleviates contraction of skin grafts via promoting macrophages M2 polarization.
  45. Mitigation of aging-related plasticity decline through taurine supplementation and environmental enrichment.
  46. Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice.
  47. A single-cell transcriptomic census of mammalian olfactory epithelium aging.
  48. Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study.
  49. Next-generation CRISPR technology for genome, epigenome and mitochondrial editing.
  50. Using AlphaFold Multimer to discover interkingdom protein-protein interactions.
  51. Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity.
  52. Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory.
  53. Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions.
  54. Transcriptome analyses reveal key features of mouse seminal vesicle during aging.
  55. Retraction: Bone morphogenetic protein-7 retards cell subculture-induced senescence of human nucleus pulposus cells through activating the PI3K/Akt pathway.
  56. Multidose transient transfection of human embryonic kidney 293 cells modulates recombinant adeno-associated virus2/5 Rep protein expression and influences the enrichment fraction of filled capsids.
  57. Tissues stay fit by balancing clearance of dying cells with regeneration.
  58. Artemisinin ameliorates thyroid function and complications in adult male hypothyroid rats via upregulation of the L1 cell adhesion molecule.
  59. From rest to repair: Safeguarding genomic integrity in quiescent cells.
  60. MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.
  61. Multi-faceted regulation of CREB family transcription factors.
  62. AI can't learn new things forever - an algorithm can fix that.
  63. OOCYTE MATURATION, BLASTOCYST AND EMBRYONIC DEVELOPMENT ARE MEDIATED AND ENHANCED VIA HORMESIS.
  1. Exp Gerontol. 2024 Aug 20. pii: S0531-5565(24)00196-7. [Epub ahead of print] 112550
    Neurobiological and anti-aging benefits of yoga: A comprehensive review of recent advances in non-pharmacological therapy.
    Qiaoyan Chen.
      Aging is an unavoidable process marked by numerous physiological and psychological changes that profoundly impact overall health and quality of life. As the global population ages, there is a growing interest in non-pharmacological therapies that can mitigate the adverse effects of aging and promote longevity. This narrative review explores the broad spectrum of non-pharmacological mechanisms offering anti-aging benefits, with a special emphasis on holistic practices such as yoga, meditation, and lifestyle interventions. These therapies influence critical biological processes, including reducing oxidative stress, modulating chronic inflammation, enhancing immune function, and preserving telomere length-key markers of cellular aging. Additionally, these practices contribute to improved cardiovascular health, musculoskeletal strength, and mental well-being, fostering a comprehensive approach to healthy aging. Yoga, for instance, combines physical postures, breath control, and meditation to enhance physical flexibility, mental clarity, and emotional balance. Meditation practices are shown to reduce stress and improve cognitive function, further supporting healthy aging. Lifestyle modifications, such as diet and regular physical activity, complement these therapies by promoting overall vitality and reducing the risk of age-related diseases. This review underscores the potential of integrating these non-pharmacological strategies into daily routines to enhance resilience against aging, improve quality of life, and extend healthspan. Furthermore, it highlights the need for continued research to fully elucidate the mechanisms by which these therapies exert their anti-aging effects and to develop evidence-based guidelines for their implementation.
    Keywords:  Aging; Cellular mechanism; Molecular mechanism; Oxidative stress; Yoga
    DOI:  https://doi.org/10.1016/j.exger.2024.112550
  2. Rejuvenation Res. 2024 Aug 20.
    Advancing Longevity: Exploring Anti-Aging Pharmaceuticals in Contemporary Clinical Trials amidst Aging Dynamics.
    Murali Krishna Moka, Melvin George, D K Sriram.
      Aging is an inevitable biological process that significantly impacts human health, leading to a decline in cellular function and an increase in cellular damage. This study elucidates the burgeoning potential of anti-aging pharmaceuticals in mitigating the thriving burden of chronic conditions linked to advancing age. It underscores the pivotal role of these pharmacotherapeutic agents in fostering longevity free from debilitating age-related afflictions, notably cardiovascular disorders, neoplastic processes, and neurodegenerative pathologies. While commendable strides have been made evident in preclinical models, it is crucial to thoroughly investigate their effectiveness and safety in human groups. Additionally, ethical concerns about fair access, societal impacts, and careful resource distribution are significant in discussions about developing and using anti-aging medications. By approaching the development and utilization of anti-aging medications with diligence and foresight, we can strive towards a future where individuals can enjoy extended lifespans free from the debilitating effects of age-related ailments.
    DOI:  https://doi.org/10.1089/rej.2024.0040
  3. Heliyon. 2024 Aug 15. 10(15): e35556
    Research on the anti-oxidant and anti-aging effects of Polygonatum kingianum saponins in Caenorhabditis elegans.
    Yaqi Huang, Yetong Wang, Jia Deng, Sijie Gao, Jiakang Qiu, Jiawei He, Tong Yang, Nianhua Tan, Shaowu Cheng, Zhenyan Song.
      Oxidative stress and its impact on aging are critical areas of research. Natural anti-oxidants, such as saponins found in Polygonatum sibiricum, hold promise as potential clinical interventions against aging. In this study, we utilized the nematode model organism, Caenorhabditis elegans, to investigate the pharmacological effects of Polygonatum sibiricum saponins (PKS) on antioxidation and anti-aging. The results demonstrated a significant anti-aging biological activity associated with PKS. Through experiments involving lifespan and stress, lipofuscin, q-PCR, and ROS measurement, we found that PKS effectively mitigated aging-related processes. Furthermore, the mechanism underlying these anti-aging effects was linked to the SKN-1 signaling pathway. PKS increased the nuclear localization of the SKN-1 transcription factor, leading to the up-regulation of downstream anti-oxidant genes, such as gst-4 and sod-3, and a substantial reduction in intracellular ROS levels within the nematode. In conclusion, our study sheds light on the anti-oxidant and anti-aging properties of PKS in C. elegans. This research not only contributes to understanding the biological mechanisms involved but also highlights the potential therapeutic applications of these natural compounds in combating aging-related processes.
    Keywords:  Anti-aging; Anti-oxidant; Caenorhabditis elegans; Polygonatum kingianum saponins; SKN-1
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e35556
  4. Aging Biol. 2024 ;pii: e20240021. [Epub ahead of print]2
    Damage-Induced Senescent Immune Cells Regulate Regeneration of the Zebrafish Retina.
    Gregory J Konar, Zachary Flickinger, Shivani Sharma, Kyle T Vallone, Charles E Lyon, Claire Doshier, Audrey Lingan, William Lyon, James G Patton.
      Zebrafish spontaneously regenerate their retinas in response to damage through the action of Müller glia (MG). Even though MG are conserved in higher vertebrates, the capacity to regenerate retinal damage is lost. Recent work has focused on the regulation of inflammation during tissue regeneration, with temporal roles for macrophages and microglia. Senescent cells that have withdrawn from the cell cycle have mostly been implicated in aging but are still metabolically active, releasing a variety of signaling molecules as part of the senescence-associated secretory phenotype. Here, we discover that in response to retinal damage, a subset of cells expressing markers of microglia/macrophages also express markers of senescence. These cells display a temporal pattern of appearance and clearance during retina regeneration. Premature removal of senescent cells by senolytic treatment led to a decrease in proliferation and incomplete repair of the ganglion cell layer after N-methyl-D-aspartate damage. Our results demonstrate a role for modulation of senescent cell responses to balance inflammation, regeneration, plasticity, and repair as opposed to fibrosis and scarring.
    DOI:  https://doi.org/10.59368/agingbio.20240021
  5. Free Radic Biol Med. 2024 Aug 15. pii: S0891-5849(24)00605-1. [Epub ahead of print]
    Oxidative Phosphorylation and Fatty Acid Oxidation in Slow-Aging Mice.
    Ahmed M Elmansi, Richard A Miller.
      Oxidative metabolism declines with aging in humans leading to multiple metabolic ailments and subsequent inflammation. In mice, there is evidence of age-related suppression of fatty acid oxidation and oxidative phosphorylation in the liver, heart, and muscles. Many interventions that extend healthy lifespan of mice have been developed, including genetic, pharmacological, and dietary interventions. In this article, we review the literature on oxidative metabolism changes in response to those interventions. We also discuss the molecular pathways that mediate those changes, and their potential as targets for future longevity interventions.
    DOI:  https://doi.org/10.1016/j.freeradbiomed.2024.08.018
  6. Biogerontology. 2024 Aug 20.
    The potential longevity-promoting hypoxic-hypercapnic environment as a measure for radioprotection.
    Elroei David, Marina Wolfson, Khachik K Muradian, Vadim E Fraifeld.
      Many biological mechanisms of aging well converge with radiation's biological effects. We used scientific insights from the field of aging to establish a novel hypoxic-hypercapnic environment (HHE) concept for radioprotection. According to this concept, HHE which possesses an anti-aging and longevity-promoting potential, should also act as a radiomitigator and radioprotector. As such, it might contribute greatly to the safety and wellbeing of individuals exposed to high levels of radiation, whether in planned events (e.g. astronauts) or in unplanned events (e.g. first responders in nuclear accidents).
    Keywords:  Aging; Hormesis; Hypercapnia; Hypoxia; Ionizing radiation; Radioprotection
    DOI:  https://doi.org/10.1007/s10522-024-10129-3
  7. Prostaglandins Leukot Essent Fatty Acids. 2024 Aug 10. pii: S0952-3278(24)00028-0. [Epub ahead of print]202 102634
    Resolvin D1 suppresses macrophage senescence and splenic fibrosis in aged mice.
    Anouk G Groenen, Masharh Lipscomb, Ramon Bossardi Ramos, Sudeshna Sadhu, Venetia Bazioti, Gabrielle Fredman, Marit Westerterp.
      Aging is associated with systemic, non-resolving inflammation and the accumulation of senescent cells. The resolution of inflammation (or inflammation-resolution) is in part mediated by the balance between specialized pro-resolving mediators (SPMs) and pro-inflammatory leukotrienes (LTs). Aged mice (i.e. 2 years of age) exhibit a significant decrease in the SPM:LT ratio in specific organs including the spleen, which suggests that this organ may exhibit heightened inflammation and may be particularly amenable to SPM therapy. Previous studies have shown that resolvin D1 (RvD1) is decreased in spleens of aged mice compared with young controls. Therefore, we asked whether treatment of RvD1 in aged mice would impact markers of cellular senescence in splenic macrophages, and downstream effects on splenic fibrosis, a hallmark of splenic aging. We found that in aged mice, both zymosan-elicited and splenic macrophages showed an increase in mRNA expression of inflammatory and eicosanoid biosynthesis genes and a dysregulation of genes involved in the cell cycle. Injections with RvD1 reversed these changes. Importantly, RvD1 also decreased splenic fibrosis, a hallmark of splenic aging. Our findings suggest that RvD1 treatment may limit several features of aging, including senescence and fibrosis in spleens from aged mice. Summary Aging is associated with systemic, low grade, non-resolving inflammation. The resolution of inflammation is in part mediated by the balance between specialized pro-resolving mediators (SPMs) and pro-inflammatory lipid mediators, like leukotrienes (LTs). A hallmark of aging is the accumulation of senescent cells that promote low grade inflammation by secreting pro-inflammatory cytokines and lipid mediators. Splenic macrophages contribute to systemic aging, and spleens of aged mice demonstrate decreased levels of the SPM called resolvin D1 (RvD1). Whether addition of RvD1 is protective in spleens of aged mice is unknown and is focus of this study. RvD1 treatment to aged mice led to decreased mRNA expression of markers of cellular senescence and inflammation in splenic macrophages compared with age-matched vehicle controls. Moreover, RvD1 decreased splenic fibrosis, which occurs due to persistent low-grade inflammation in aging. Promoting inflammation resolution with RvD1 thus limits macrophage senescence, pro-inflammatory signals and established splenic fibrosis in aging.
    Keywords:  Aging; Fibrosis; Resolvins; Senescence; Spleen
    DOI:  https://doi.org/10.1016/j.plefa.2024.102634
  8. J Biochem Mol Toxicol. 2024 Sep;38(9): e23812
    The influential responsibility of sirtuins in senescence and associated diseases: A review.
    Deepak Mishra, Lucy Mohapatra, Alok S Tripathi, Shravan Kumar Paswan.
      Aging is a process of time-associated depletion in the physiological functions, essential for the survival and reproducibility of living beings. Some age-related disorders can be successfully controlled with some biomedical techniques or pharmaceutical approaches. There are some precise remedies that demonstrate conspicuous promise in the preclinical and clinical setup of extending lifespan or enhancing health by altering natural senescence. The sirtuin family of proteins is one of the most favorable targets for antiaging strategies. Sirtuins were initially identified as transcription repressors in yeast, but today they are known to exist in bacteria and eukaryotes, as well as humans. The SIRT (1-7) family of proteins in humans is made up of seven members, each of which has either mono-ADP ribosyl transferase or deacetylase activity. Researchers suggest that sirtuins are essential for cell metabolism and play a major role in how cells react to various stimuli, such as oxidative or genotoxic stress. A healthy lifestyle, which includes exercise and a balanced diet, has been demonstrated to impact health span by adjusting the levels of sirtuins, suggesting the involvement of sirtuins in extending human longevity. The hunt for sirtuin activators is among the most extensive and comprehensive research subjects in the present scenario. Some optimism has been generated to investigate antiaging therapies by natural compounds, such as curcumin and others. This review article highlights the role of sirtuins in native senescence and their primordial roles in the progression of several life-threatening diseases. Further, it also provides recent information on the sirtuin activators and inhibitors and their therapeutic benefits.
    Keywords:  SIRT‐inhibitors; SIRT‐promoters; cancer; diabetes; neurodegeneration; obesity; senescence; sirtuins
    DOI:  https://doi.org/10.1002/jbt.23812
  9. Ageing Res Rev. 2024 Aug 15. pii: S1568-1637(24)00274-5. [Epub ahead of print] 102456
    Consolidating multiple evolutionary theories of ageing suggests a need for new approaches to study genetic contributions to ageing decline.
    Luke Slade, Timothy Etheridge, Nathaniel J Szewczyk.
      Understanding mechanisms of ageing remains a complex challenge for biogerontologists, but recent adaptations of evolutionary ageing theories offer a compelling lens in which to view both age-related molecular and physiological deterioration. Ageing is commonly associated with progressive declines in biochemical and molecular processes resulting from damage accumulation, yet the role of continued developmental gene activation is less appreciated. Natural selection pressures are at their highest in youthful periods to modify gene expression towards maximising reproductive capacity. After sexual maturation, selective pressure diminishes, subjecting individuals to maladaptive pleiotropic gene functions that were once beneficial for developmental growth but become pathogenic later in life. Due to this selective 'shadowing' in ageing, mechanisms to counter such hyper/hypofunctional genes are unlikely to evolve. Interventions aimed at targeting gene hyper/hypofunction during ageing might, therefore, represent an attractive therapeutic strategy. The nematode Caenorhabditis elegans offers a strong model for post-reproductive mechanistic and therapeutic investigations, yet studies examining the mechanisms of, and countermeasures against, ageing decline largely intervene from larval stages onwards. Importantly, however, lifespan extending conditions frequently impair early-life fitness and fail to correspondingly increase healthspan. Here, we consolidate multiple evolutionary theories of ageing and discuss data supporting hyper/hypofunctional changes at a global molecular and functional level in C. elegans, and how classical lifespan-extension mutations alter these dynamics. The relevance of such mutant models for exploring mechanisms of ageing are discussed, highlighting that post-reproductive gene optimisation represents a more translatable approach for C. elegans research that is not constrained by evolutionary trade-offs. Where some genetic mutations in C. elegans that promote late-life health map accordingly with healthy ageing in humans, other widely used genetic mutations that extend worm lifespan are associated with life-limiting pathologies in people. Lifespan has also become the gold standard for quantifying 'ageing', but we argue that gerospan compression (i.e., 'healthier' ageing) is an appropriate goal for anti-ageing research, the mechanisms of which appear distinct from those regulating lifespan alone. There is, therefore, an evident need to re-evaluate experimental approaches to study the role of hyper/hypofunctional genes in ageing in C. elegans.
    Keywords:  C. elegans; Hyperfunction; ageing; gene optimisation; healthspan
    DOI:  https://doi.org/10.1016/j.arr.2024.102456
  10. J Cosmet Dermatol. 2024 Aug 20.
    Investigation of the anti-skin aging effects of taurine through mendelian randomization analysis of its relationship with immune cells.
    Hongtao Liu, Honglai Zhen, Siyuan Zhou, Quan Lin.
      BACKGROUND: Aging skin, exacerbated by external factors like UV radiation and pollutants, is a major cosmetic concern. Taurine, renowned for its antioxidant and anti-inflammatory properties, may combat skin aging. We performed mendelian randomization (MR) analysis to investigate the causal link between taurine and immune cells linked to skin aging.OBJECTIVES: To investigate the association between taurine and immune cells using mendelian randomization, to thereby explore the mechanism through which taurine exerts anti-aging effects on the skin via immune modulation.
    METHODS: A MR approach was employed using taurine-level data from the Ieu Open GWAS Project and immunocyte traits from a large European cohort. MR-Egger regression, weighted median estimation, and inverse variance weighting all provided statistical insights into causality. Sensitivity analyses assessed the heterogeneity and pleiotropy among the genetic instruments used.
    RESULTS: MR analysis identified a causal relationship between taurine levels and 10 immunocyte phenotypes, with taurine found to be negatively and positively associated with three and seven phenotypes, respectively. Sensitivity analysis revealed no significant heterogeneity or pleiotropy, suggesting reliable MR findings.
    CONCLUSION: This study provides insights into the immunological pathways by which taurine contributes to skin anti-aging effects, suggesting that increasing taurine levels could offer a novel strategy for anti-aging skincare.
    Keywords:  Mendelian randomization; anti‐aging treatment; immune cells; monocytes; taurine
    DOI:  https://doi.org/10.1111/jocd.16515
  11. Mol Biol Rep. 2024 Aug 19. 51(1): 917
    Aging and physiological barriers: mechanisms of barrier integrity changes and implications for age-related diseases.
    Ilya Solovev, Alena Sergeeva, Anastasya Geraskina, Mikhail Shaposhnikov, Maria Vedunova, Olga Borysova, Alexey Moskalev.
      The phenomenon of compartmentalization is one of the key traits of life. Biological membranes and histohematic barriers protect the internal environment of the cell and organism from endogenous and exogenous impacts. It is known that the integrity of these barriers decreases with age due to the loss of homeostasis, including age-related gene expression profile changes and the abnormal folding/assembly, crosslinking, and cleavage of barrier-forming macromolecules in addition to morphological changes in cells and tissues. The critical molecular and cellular mechanisms involved in physiological barrier integrity maintenance and aging-associated changes in their functioning are reviewed on different levels: molecular, organelle, cellular, tissue (histohematic, epithelial, and endothelial barriers), and organ one (skin). Biogerontology, which studies physiological barriers in the aspect of age, is still in its infancy; data are being accumulated, but there is no talk of the synthesis of complex theories yet. This paper mainly presents the mechanisms that will become targets of anti-aging therapy only in the future, possibly: pharmacological, cellular, and gene therapies, including potential geroprotectors, hormetins, senomorphic drugs, and senolytics.
    Keywords:  Aging; Barrier integrity maintenance; Histohematic barriers; Physiological barriers; Target molecules
    DOI:  https://doi.org/10.1007/s11033-024-09833-7
  12. Biogerontology. 2024 Aug 20.
    Oxidative stress-induced gene expression changes in prostate epithelial cells in vitro reveal a robust signature of normal prostatic senescence and aging.
    Samael Olascoaga, Jorge I Castañeda-Sánchez, Mina Königsberg, Humberto Gutierrez, Norma Edith López-Diazguerrero.
      Oxidative stress has long been postulated to play an essential role in aging mechanisms, and numerous forms of molecular damage associated with oxidative stress have been well documented. However, the extent to which changes in gene expression in direct response to oxidative stress are related to actual cellular aging, senescence, and age-related functional decline remains unclear. Here, we ask whether H2O2-induced oxidative stress and resulting gene expression alterations in prostate epithelial cells in vitro reveal gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease. While a broad range of significant changes observed in the expression of non-coding transcripts implicated in senescence-related responses, we also note an overrepresentation of gene-splicing events among differentially expressed protein-coding genes induced by H2O2. Additionally, the collective expression of these H2O2-induced DEGs is linked to age-related pathological dysfunction, with their protein products exhibiting a dense network of protein-protein interactions. In contrast, co-expression analysis of available gene expression data reveals a naturally occurring highly coordinated expression of H2O2-induced DEGs in normally aging prostate tissue. Furthermore, we find that oxidative stress-induced DEGs statistically overrepresent well-known senescence-related signatures. Our results show that oxidative stress-induced gene expression in prostate epithelial cells in vitro reveals gene regulatory changes typically observed in naturally aging prostate tissue and age-related prostate disease.
    Keywords:  Age related diseases; Ageing; Alternative splicing; GCNs; Oxidative stress; Prostate; SIPS; Senescence; Transcriptome
    DOI:  https://doi.org/10.1007/s10522-024-10126-6
  13. J Cosmet Dermatol. 2024 Aug 19.
    Novel Thermus thermophilus and Bacillus subtilis mixed-culture ferment extract provides potent skin benefits in vitro and protects skin from aging.
    Jingyi Wang, Hu Huang, Kan Tao, Lili Guo, Xincheng Hu, Huailong Chang.
      BACKGROUND: Skin aging is one of the most abundant aging-related disorders that can be accelerated by excessive exposure to ultraviolet irradiation. Topically applied fermented skincare ingredients have gained mounting attentions due to their high concentration of various skin nourishing nutrients and bioactive components and low skin irritation potency.AIMS: In the present study, we aim to fully demonstrate the skin-related benefits of a novel extract of Thermus thermophilus and Bacillus subtilis mixed-culture ferment (TBFE).
    METHODS: TBFE was prepared through an innovative mixed-culture fermentation process. The contents of nutrients and bioactive ingredients were quantified by different methods accordingly. Both in vitro tests and randomized controlled human trial were utilized to further demonstrate multifaceted beneficial effects on human skin, as well as the potential mechanisms.
    RESULTS: Our results showed that TBFE upregulated the expression of type IV collagen, elastin, aquaporin-3, and dermal-epidermal junction markers, while inhibited production of melanin, in different skin cell models. Moreover, TBFE inhibited the generation of reactive oxygen species and pro-inflammatory mediators induced by ultraviolet irradiation in normal human keratinocytes, while stimulated autophagy in senescent keratinocytes. Results from clinical studies confirmed those in vitro findings, demonstrating that TBFE at 5% and 20% concentration provides anti-aging properties in subjects with sensitive skin, in terms of improving wrinkles, moisturization, and skin lightening.
    CONCLUSIONS: In summary, we demonstrate that a novel mixed-culture ferment extract has promising anti-aging effects, which may be attributed to anti-oxidation, anti-inflammation, and promotion of autophagy in skin cells.
    Keywords:  anti‐aging; anti‐inflammation; anti‐oxidation; autophagy; mixed‐culture fermentation
    DOI:  https://doi.org/10.1111/jocd.16531
  14. FASEB J. 2024 Aug 31. 38(16): e70000
    Research progress on interferon and cellular senescence.
    Da Wang, Kaixian Chen, Zheng Wang, Huali Wu, Yiming Li.
      Since the 12 major signs of aging were revealed in 2023, people's interpretation of aging will go further, which is of great significance for understanding the occurrence, development, and intervention in the aging process. As one of the 12 major signs of aging, cellular senescence refers to the process in which the proliferation and differentiation ability of cells decrease under stress stimulation or over time, often manifested as changes in cell morphology, cell cycle arrest, and decreased metabolic function. Interferon (IFN), as a secreted ligand for specific cell surface receptors, can trigger the transcription of interferon-stimulated genes (ISGs) and play an important role in cellular senescence. In addition, IFN serves as an important component of SASP, and the activation of the IFN signaling pathway has been shown to contribute to cell apoptosis and senescence. It is expected to delay cellular senescence by linking IFN with cellular senescence and studying the effects of IFN on cellular senescence and its mechanism. This article provides a review of the research on the relationship between IFN and cellular senescence by consulting relevant literature.
    Keywords:  body aging; cellular senescence; interaction; interferon; mechanism of action
    DOI:  https://doi.org/10.1096/fj.202400808RR
  15. Biogerontology. 2024 Aug 21.
    The role of phagocytic cells in aging: insights from vertebrate and invertebrate models.
    Brecht Driesschaert, Lucas Mergan, Cristiano Lucci, Caroline Simon, Dulce Santos, Lies De Groef, Liesbet Temmerman.
      While the main role of phagocytic scavenger cells consists of the neutralization and elimination of pathogens, they also keep the body fluids clean by taking up and breaking down waste material. Since a build-up of waste is thought to contribute to the aging process, these cells become particularly pertinent in the research field of aging. Nevertheless, a direct link between their scavenging functions and the aging process has yet to be established. Integrative approaches involving various model organisms hold promise to elucidate this potential, but are lagging behind since the diversity and evolutionary relationship of these cells across animal species remain unclear. In this perspective, we review the current knowledge associating phagocytic scavenger cells with aging in vertebrate and invertebrate animals, as well as put forward important questions for further exploration. Additionally, we highlight future challenges and propose a constructive approach for tackling them.
    Keywords:  Aging; Coelomocyte; Granulocyte; Macrophage; Phagocytosis; Plasmatocyte
    DOI:  https://doi.org/10.1007/s10522-024-10131-9
  16. Stem Cells. 2024 Aug 22. pii: sxae047. [Epub ahead of print]
    Integrin-linked kinase control dental pulp stem cell senescence via the mTOR signaling pathway.
    Lu Chen, Xiping Wang, Sha Tian, Linxi Zhou, Li Wang, Xiaohan Liu, Zihan Yang, Guiqiang Fu, Xingguang Liu, Chen Ding, Duohong Zou.
      Human dental pulp stem cells (HDPSCs) showed an age-dependent decline in proliferation and differentiation capacity. Decline in proliferation and differentiation capacity affect the dental stromal tissue homeostasis and impair the regenerative capability of HDPSCs. However, which age-correlated proteins regulate the senescence of HDPSCs remain unknown. Our study investigated the proteomic characteristics of HDPSCs isolated from subjects of different ages and explored the molecular mechanism of age-related changes in HDPSCs. Our study showed that the proliferation and osteogenic differentiation of HDPSCs were decreased, while the expression of aging-related genes (p21, p53) and proportion of senescence-associated β-galactosidase (SA-β-gal)-positive cells were increased with aging. The bioinformatic analysis identified that significant proteins positively correlated with age were enriched in response to the mTOR signaling pathway (ILK, MAPK3, mTOR, STAT1 and STAT3). We demonstrated that OSU-T315, an inhibitor of integrin-linked kinase (ILK), rejuvenated aged HDPSCs, similar to rapamycin (an inhibitor of mTOR). Treatment with OSU-T315 decreased the expression of aging-related genes (p21, p53) and proportion of SA-β-gal-positive cells in HDPSCs isolated from old (O-HDPSCs). Additionally, OSU-T315 promoted the osteoblastic differentiation capacity of O-HDPSCs in vitro and bone regeneration of O-HDPSCs in rat calvarial bone defects model. Our study indicated that the proliferation and osteoblastic differentiation of HDPSCs were impaired with aging. Notably, the ILK/AKT/mTOR/STAT1 signaling pathway may be a major factor in the regulation of HDPSC senescence, which help to provide interventions for HDPSC senescence.
    Keywords:  HDPSCs; ILK; cellular senescence; osteogenesis; proteomic
    DOI:  https://doi.org/10.1093/stmcls/sxae047
  17. Maturitas. 2024 Aug 10. pii: S0378-5122(24)00186-5. [Epub ahead of print]189 108091
    The impact of carnosine on biological ageing - A geroscience approach.
    Qian Wang, Saeede Saadati, Robel Hussen Kabthymer, Laura Kate Gadanec, Amy Lawton, Nicholas Tripodi, Vasso Apostolopoulos, Barbora de Courten, Jack Feehan.
      Biological ageing involves a gradual decline in physiological function and resilience, marked by molecular, cellular, and systemic changes across organ systems. Geroscience, an interdisciplinary field, studies these mechanisms and their role in age-related diseases. Genomic instability, inflammation, telomere attrition, and other indicators contribute to conditions like cardiovascular disease and neurodegeneration. Geroscience identifies geroprotectors, such as resveratrol and metformin, targeting ageing pathways to extend the healthspan. Carnosine, a naturally occurring dipeptide (b-alanine and l-histidine), has emerged as a potential geroprotector with antioxidative, anti-inflammatory, and anti-glycating properties. Carnosine's benefits extend to muscle function, exercise performance, and cognitive health, making it a promising therapeutic intervention for healthy ageing and oxidative stress-related pathologies. In this review, we summarize the evidence describing carnosine's effects in promoting healthy ageing, providing new insights into improving geroscience.
    Keywords:  Ageing; Carnosine; Geroprotective; Geroscience
    DOI:  https://doi.org/10.1016/j.maturitas.2024.108091
  18. Trends Biochem Sci. 2024 Aug 20. pii: S0968-0004(24)00164-6. [Epub ahead of print]
    Cellular oxidants and the proteostasis network: balance between activation and destruction.
    Agnes Ulfig, Ursula Jakob.
      Loss of protein homeostasis (proteostasis) is a common hallmark of aging and age-associated diseases. Considered as the guardian of proteostasis, the proteostasis network (PN) acts to preserve the functionality of proteins during their lifetime. However, its activity declines with age, leading to disease manifestation. While reactive oxygen species (ROS) were traditionally considered culprits in this process, recent research challenges this view. While harmful at high concentrations, moderate ROS levels protect the cell against age-mediated onset of proteotoxicity by activating molecular chaperones, stress response pathways, and autophagy. This review explores the nuanced roles of ROS in proteostasis and discusses the most recent findings regarding the redox regulation of the PN and its potential in extending healthspan and delaying age-related pathologies.
    Keywords:  aging; neurodegeneration; oxidative stress; protein aggregation; protein homeostasis; protein misfolding
    DOI:  https://doi.org/10.1016/j.tibs.2024.07.001
  19. J Gerontol A Biol Sci Med Sci. 2024 Aug 22. pii: glae205. [Epub ahead of print]
    The effect of axenic dietary restriction on the age-related changes in C. elegans.
    Ping Wu, Lieselot Vandemeulebroucke, Myriam Claeys, Wim Bert, Bart P Braeckman.
      Axenic dietary restriction (ADR) is highly effective in extending lifespan of C. elegans but its effects on healthspan improvement is less well characterized. Using transmission electron microscopy, morphometric analyses, and functional assays, we found ADR can preserve tissue ultrastructure, including the cuticle, epidermis, and intestinal lumen, and reduce age-associated pathologies like gonad degeneration, uterine tumor clusters, pharyngeal deterioration, and intestinal atrophy. However, there was no notable improvement in behavioral and functional metrics. Our results underscore that lifespan extension through ADR does not inherently translate to broad healthspan improvements.
    Keywords:   C. elegans ; axenic dietary restriction; healthspan; lifespan
    DOI:  https://doi.org/10.1093/gerona/glae205
  20. Front Vet Sci. 2024 ;11 1430861
    DNA damage (8-OHdG) and telomere length in captive Psittacidae birds with different longevity.
    Angélica Domínguez-de-Barros, Inés Sifaoui, Roberto Dorta-Guerra, Jacob Lorenzo-Morales, Rafael Castro-Fuentes, Elizabeth Córdoba-Lanús.
      Aging is a complex process influenced by internal and external factors. Oxidative stress damages DNA, leading to 8-hydroxy-2' deoxyguanosine formation (8-OHdG). Telomere shortening is considered a biomarker of aging and oxidative stress may enhance its attrition. The ability to manage and repair oxidative stress varies among species and life histories. Avian species, such as Psittacidae birds, exhibit exceptional lifespans despite their physiological characteristics that might suggest otherwise. This study investigates 8-OHdG levels in serum samples from long- and short-lived birds of the order Psittaciformes, examining their relationship with telomere length and antioxidant capacity based on lifespan strategies. Among 43 individuals analyzed 26 belonged to the "long-lived species" group and 17 belonged to the "short-lived species" one. Relative telomere length (rTL) was measured in DNA isolated from whole blood by qPCR, and oxidative stress markers, such as Total Antioxidant Capacity (TAC) and 8-OHdG, were determined by spectrophotometry in serum samples. Long-lived birds had longer rTL than short-lived ones [1.308 ± 0.11 vs. 0.565 ± 0.13, (p < 0.001)]. On the contrary, short-lived birds showed more DNA damage than their counterparts [3.847 ± 0.351 vs. 2.012 ± 0.308, respectively, (p < 0.001)]. Old birds had shorter rTL than young ones, for both longevity groups (p < 0.001). Although no correlation was found between 8-OHdG levels and age, nor 8-OHdG and telomere length, long-lived birds exhibited 75.42-unit increased TAC levels when increased 8-OHdG concentrations (p = 0.046). These findings highlight distinct patterns of telomere length and oxidative stress influenced by lifespan strategies among avian longevity groups.
    Keywords:  8-OHdG; DNA damage; Psittacidae; birds; longevity; oxidative stress; telomeres
    DOI:  https://doi.org/10.3389/fvets.2024.1430861
  21. Nature. 2024 Aug 21.
    Short-term post-fast refeeding enhances intestinal stemness via polyamines.
    Shinya Imada, Saleh Khawaled, Heaji Shin, Sven W Meckelmann, Charles A Whittaker, Renan Oliveira Corrêa, Chiara Alquati, Yixin Lu, Guodong Tie, Dikshant Pradhan, Gizem Calibasi-Kocal, Luiza Martins Nascentes Melo, Gabriele Allies, Jonas Rösler, Pia Wittenhofer, Jonathan Krystkiewicz, Oliver J Schmitz, Jatin Roper, Marco Aurelio Ramirez Vinolo, Luigi Ricciardiello, Evan C Lien, Matthew G Vander Heiden, Ramesh A Shivdasani, Chia-Wei Cheng, Alpaslan Tasdogan, Ömer H Yilmaz.
      For over a century, fasting regimens have improved health, lifespan and tissue regeneration in diverse organisms, including humans1-6. However, how fasting and post-fast refeeding affect adult stem cells and tumour formation has yet to be explored in depth. Here we demonstrate that post-fast refeeding increases intestinal stem cell (ISC) proliferation and tumour formation; post-fast refeeding augments the regenerative capacity of Lgr5+ ISCs, and loss of the tumour suppressor gene Apc in post-fast-refed ISCs leads to a higher tumour incidence in the small intestine and colon than in the fasted or ad libitum-fed states, demonstrating that post-fast refeeding is a distinct state. Mechanistically, we discovered that robust mTORC1 induction in post-fast-refed ISCs increases protein synthesis via polyamine metabolism to drive these changes, as inhibition of mTORC1, polyamine metabolite production or protein synthesis abrogates the regenerative or tumorigenic effects of post-fast refeeding. Given our findings, fast-refeeding cycles must be carefully considered and tested when planning diet-based strategies for regeneration without increasing cancer risk, as post-fast refeeding leads to a burst in stem-cell-driven regeneration and tumorigenicity.
    DOI:  https://doi.org/10.1038/s41586-024-07840-z
  22. J Transl Med. 2024 Aug 22. 22(1): 779
    Epidermal stem cells: skin surveillance and clinical perspective.
    Xin Tang, Jiaqi Wang, Jiaoling Chen, Wanting Liu, Pei Qiao, Huiyi Quan, Zhiguo Li, Erle Dang, Gang Wang, Shuai Shao.
      The skin epidermis is continually influenced by a myriad of internal and external elements. At its basal layer reside epidermal stem cells, which fuels epidermal renovation and hair regeneration with powerful self-renewal ability, as well as keeping diverse signals that direct their activity under surveillance with quick response. The importance of epidermal stem cells in wound healing and immune-related skin conditions has been increasingly recognized, and their potential for clinical applications is attracting attention. In this review, we delve into recent advancements and the various physiological and psychological factors that govern distinct epidermal stem cell populations, including psychological stress, mechanical forces, chronic aging, and circadian rhythm, as well as providing an overview of current methodological approaches. Furthermore, we discuss the pathogenic role of epidermal stem cells in immune-related skin disorders and their potential clinical applications.
    Keywords:  Aging; Epidermal stem cells; Immune-related skin disorders; Regeneration; Wound healing
    DOI:  https://doi.org/10.1186/s12967-024-05600-1
  23. Aging (Albany NY). 2024 Aug 18. 16
    Targeting multiple hallmarks of mammalian aging with combinations of interventions.
    Alexander Y Panchin, Anna Ogmen, Artem S Blagodatski, Anastasia Egorova, Mikhail Batin, Timofey Glinin.
      Aging is currently viewed as a result of multiple biological processes that manifest themselves independently, reinforce each other and in their totality lead to the aged phenotype. Genetic and pharmaceutical approaches targeting specific underlying causes of aging have been used to extend the lifespan and healthspan of model organisms ranging from yeast to mammals. However, most interventions display only a modest benefit. This outcome is to be expected if we consider that even if one aging process is successfully treated, other aging pathways may remain intact. Hence solving the problem of aging may require targeting not one but many of its underlying causes at once. Here we review the challenges and successes of combination therapies aimed at increasing the lifespan of mammals and propose novel directions for their development. We conclude that both additive and synergistic effects on mammalian lifespan can be achieved by combining interventions that target the same or different hallmarks of aging. However, the number of studies in which multiple hallmarks were targeted simultaneously is surprisingly limited. We argue that this approach is as promising as it is understudied.
    Keywords:  aging; combination therapy; hallmarks; lifespan and healthspan; mouse; synergistic effect
    DOI:  https://doi.org/10.18632/aging.206078
  24. EMBO Rep. 2024 Aug 16.
    Inflated expectations: the strange craze for translational research on aging : Given existing confusion about the basic science of aging, why the high optimism in the private sector about the prospects of developing anti-aging treatments?
    David Gems, Simon Okholm, Maёl Lemoine.
      
    DOI:  https://doi.org/10.1038/s44319-024-00226-2
  25. Nat Commun. 2024 Aug 21. 15(1): 7144
    FOXO-regulated OSER1 reduces oxidative stress and extends lifespan in multiple species.
    Jiangbo Song, Zhiquan Li, Lei Zhou, Xin Chen, Wei Qi Guinevere Sew, Héctor Herranz, Zilu Ye, Jesper Velgaard Olsen, Yuan Li, Marianne Nygaard, Kaare Christensen, Xiaoling Tong, Vilhelm A Bohr, Lene Juel Rasmussen, Fangyin Dai.
      FOXO transcription factors modulate aging-related pathways and influence longevity in multiple species, but the transcriptional targets that mediate these effects remain largely unknown. Here, we identify an evolutionarily conserved FOXO target gene, Oxidative stress-responsive serine-rich protein 1 (OSER1), whose overexpression extends lifespan in silkworms, nematodes, and flies, while its depletion correspondingly shortens lifespan. In flies, overexpression of OSER1 increases resistance to oxidative stress, starvation, and heat shock, while OSER1-depleted flies are more vulnerable to these stressors. In silkworms, hydrogen peroxide both induces and is scavenged by OSER1 in vitro and in vivo. Knockdown of OSER1 in Caenorhabditis elegans leads to increased ROS production and shorter lifespan, mitochondrial fragmentation, decreased ATP production, and altered transcription of mitochondrial genes. Human proteomic analysis suggests that OSER1 plays roles in oxidative stress response, cellular senescence, and reproduction, which is consistent with the data and suggests that OSER1 could play a role in fertility in silkworms and nematodes. Human studies demonstrate that polymorphic variants in OSER1 are associated with human longevity. In summary, OSER1 is an evolutionarily conserved FOXO-regulated protein that improves resistance to oxidative stress, maintains mitochondrial functional integrity, and increases lifespan in multiple species. Additional studies will clarify the role of OSER1 as a critical effector of healthy aging.
    DOI:  https://doi.org/10.1038/s41467-024-51542-z
  26. Cell Metab. 2024 Aug 16. pii: S1550-4131(24)00291-2. [Epub ahead of print]
    Misregulation of mitochondrial 6mA promotes the propagation of mutant mtDNA and causes aging in C. elegans.
    Anne Hahn, Grace Ching Ching Hung, Arnaud Ahier, Chuan-Yang Dai, Ina Kirmes, Brian M Forde, Daniel Campbell, Rachel Shin Yie Lee, Josiah Sucic, Tessa Onraet, Steven Zuryn.
      In virtually all eukaryotes, the mitochondrial DNA (mtDNA) encodes proteins necessary for oxidative phosphorylation (OXPHOS) and RNAs required for their synthesis. The mechanisms of regulation of mtDNA copy number and expression are not completely understood but crucially ensure the correct stoichiometric assembly of OXPHOS complexes from nuclear- and mtDNA-encoded subunits. Here, we detect adenosine N6-methylation (6mA) on the mtDNA of diverse animal and plant species. This modification is regulated in C. elegans by the DNA methyltransferase DAMT-1 and demethylase ALKB-1. Misregulation of mtDNA 6mA through targeted modulation of these activities inappropriately alters mtDNA copy number and transcript levels, impairing OXPHOS function, elevating oxidative stress, and shortening lifespan. Compounding these defects, mtDNA 6mA hypomethylation promotes the cross-generational propagation of a deleterious mtDNA. Together, these results reveal that mtDNA 6mA is highly conserved among eukaryotes and regulates lifespan by influencing mtDNA copy number, expression, and heritable mutation levels in vivo.
    Keywords:  6mA; ROS; aging; epigenetics; heteroplasmy; lifespan; mitochondria; mitochondrial genome; mtDNA; oxidative stress
    DOI:  https://doi.org/10.1016/j.cmet.2024.07.020
  27. DNA Repair (Amst). 2024 Aug 08. pii: S1568-7864(24)00117-4. [Epub ahead of print]142 103741
    DNA synthesis across DNA hairpins by human PrimPol.
    Elizaveta O Boldinova, Andrey G Baranovskiy, Daria Esyunina, Tahir H Tahirov, Alena V Makarova.
      PrimPol is a human DNA primase involved in DNA damage tolerance pathways by restarting DNA replication downstream of DNA lesions and non-canonical DNA structures. Activity and affinity to DNA relays on the interaction of PrimPol with replication protein A (RPA). In this work, we report that PrimPol has an intrinsic ability to copy DNA hairpins with a stem length of 5-9 base pairs (bp) but shows pronounced pausing of DNA synthesis. RPA greatly stimulates DNA synthesis across inverted DNA repeats by PrimPol. Moreover, deletion of the C-terminal RPA binding motif (RBM) facilitates DNA hairpin bypass and makes it independent of RPA. This work supports the idea that RBM is a negative regulator of PrimPol and its interaction with RPA is required to achieve the fully active state.
    Keywords:  DNA hairpins; DNA replication; PrimPol; RPA
    DOI:  https://doi.org/10.1016/j.dnarep.2024.103741
  28. Regen Ther. 2024 Jun;26 508-519
    Adipose-derived stem cell therapy for spinal cord injuries: Advances, challenges, and future directions.
    Yusuke Shimizu, Edward Hosea Ntege, Eisaku Takahara, Naoki Matsuura, Rikako Matsuura, Kota Kamizato, Yoshikazu Inoue, Yoshihiro Sowa, Hiroshi Sunami.
      Spinal cord injury (SCI) has limited treatment options for regaining function. Adipose-derived stem cells (ADSCs) show promise owing to their ability to differentiate into multiple cell types, promote nerve cell survival, and modulate inflammation. This review explores ADSC therapy for SCI, focusing on its potential for improving function, preclinical and early clinical trial progress, challenges, and future directions. Preclinical studies have demonstrated ADSC transplantation's effectiveness in promoting functional recovery, reducing cavity formation, and enhancing nerve regrowth and myelin repair. To improve ADSC efficacy, strategies including genetic modification and combination with rehabilitation are being explored. Early clinical trials have shown safety and feasibility, with some suggesting motor and sensory function improvements. Challenges remain for clinical translation, including optimizing cell survival and delivery, determining dosing, addressing tumor formation risks, and establishing standardized protocols. Future research should focus on overcoming these challenges and exploring the potential for combining ADSC therapy with other treatments, including rehabilitation and medication.
    Keywords:  Adipose-derived stem cells; Cell therapy; Functional recovery; Neuroregeneration; Paralysis; Spinal cord injury
    DOI:  https://doi.org/10.1016/j.reth.2024.07.007
  29. Heliyon. 2024 Aug 15. 10(15): e35359
    IGFBP7 mediates oxLDL-induced human vascular endothelial cell injury by suppressing the expression of SIRT1.
    Jiaju Sun, Qingyong Zheng, Kaijia Wu.
      Endothelial cell injury plays an important role in initiating atherosclerotic lesion formation. Insulin-like growth factor binding protein 7 (IGFBP7) is known to modulate the behaviors of tumor-associated endothelial cells. This study was conducted to test whether IGFBP7 is involved in endothelial cell injury during atherosclerosis. Oxidized low-density lipoprotein (oxLDL) treatment was used to mimic atherosclerosis-related endothelial cell apoptosis and inflammation response. Small interfering RNA (siRNA) technology was employed to deplete IGFBP7 expression in human aortic endothelial cells (HAECs). HAECs were exposed to recombinant human IGFBP7 protein to evaluate the function of IGFBP7. Notably, IGFBP7 expression in HAECs was induced by oxLDL treatment. Knockdown of IGFBP7 or treatment with anti-IGFBP7 abolished oxLDL-induced apoptosis and inflammation in HAECs. Moreover, recombinant IGFBP7 (40 ng/mL but not 25 ng/mL) promoted apoptosis and inflammation in HAECs. IGFBP7 co-localized with CD93 on the surface of HAECs. A mechanistic investigation uncovered that IGFBP7 induced endothelial cell injury through interaction with CD93 and reduction of SIRT1 expression via an autocrine manner. Overexpression of SIRT1 rescued IGFBP7-induced phenotype in HAECs. Taken together, IGFBP7 is induced by oxLDL and mediates oxLDL-induced endothelial cell apoptosis and inflammation, likely through downregulation of SIRT1. These observations support a rationale to prevent atherosclerosis by targeting IGFBP7 activity.
    Keywords:  Atherosclerosis; Endothelial dysfunction; IGFBP7; SIRT1
    DOI:  https://doi.org/10.1016/j.heliyon.2024.e35359
  30. Nat Commun. 2024 Aug 20. 15(1): 7138
    RIOK2 transcriptionally regulates TRiC and dyskerin complexes to prevent telomere shortening.
    Shrestha Ghosh, Mileena T Nguyen, Ha Eun Choi, Maximilian Stahl, Annemarie Luise Kühn, Sandra Van der Auwera, Hans J Grabe, Henry Völzke, Georg Homuth, Samuel A Myers, Cory M Hogaboam, Imre Noth, Fernando J Martinez, Gregory A Petsko, Laurie H Glimcher.
      Telomere shortening is a prominent hallmark of aging and is emerging as a characteristic feature of Myelodysplastic Syndromes (MDS) and Idiopathic Pulmonary Fibrosis (IPF). Optimal telomerase activity prevents progressive shortening of telomeres that triggers DNA damage responses. However, the upstream regulation of telomerase holoenzyme components remains poorly defined. Here, we identify RIOK2, a master regulator of human blood cell development, as a critical transcription factor for telomere maintenance. Mechanistically, loss of RIOK2 or its DNA-binding/transactivation properties downregulates mRNA expression of both TRiC and dyskerin complex subunits that impairs telomerase activity, thereby causing telomere shortening. We further show that RIOK2 expression is diminished in aged individuals and IPF patients, and it strongly correlates with shortened telomeres in MDS patient-derived bone marrow cells. Importantly, ectopic expression of RIOK2 alleviates telomere shortening in IPF patient-derived primary lung fibroblasts. Hence, increasing RIOK2 levels prevents telomere shortening, thus offering therapeutic strategies for telomere biology disorders.
    DOI:  https://doi.org/10.1038/s41467-024-51336-3
  31. Front Pharmacol. 2024 ;15 1430284
    Role of Curcuma longae Rhizoma in medical applications: research challenges and opportunities.
    Peng Zhang, Hong Liu, Yuan Yu, Shiyang Peng, Shaomi Zhu.
      Curcuma longae Rhizoma, commonly known as turmeric, is extensively utilized not only in Traditional Chinese Medicine (TCM) but also across various traditional medicine systems worldwide. It is renowned for its effectiveness in removing blood stasis, promoting blood circulation, and relieving pain. The primary bioactive metabolites of Curcuma longae Rhizoma-curcumin, β-elemene, curcumol, and curdione-have been extensively studied for their pharmacological benefits. These include anti-tumor properties, cardiovascular and cerebrovascular protection, immune regulation, liver protection, and their roles as analgesics, anti-inflammatories, antivirals, antibacterials, hypoglycemics, and antioxidants. This review critically examines the extensive body of research regarding the mechanisms of action of Curcuma longae Rhizoma, which engages multiple molecular targets and signaling pathways such as NF-κB, MAPKs, and PI3K/AKT. The core objective of this review is to assess how the main active metabolites of turmeric interact with these molecular systems to achieve therapeutic outcomes in various clinical settings. Furthermore, we discuss the challenges related to the bioavailability of these metabolites and explore potential methods to enhance their therapeutic effects. By doing so, this review aims to provide fresh insights into the optimization of Curcuma longae Rhizoma for broader clinical applications.
    Keywords:  Curcuma longae Rhizoma; curcumin; curcumol; curdione; pharmacological activities; β-elemene
    DOI:  https://doi.org/10.3389/fphar.2024.1430284
  32. Regen Biomater. 2024 ;11 rbae085
    Controllable self-assembly of tyrosine-rich triblock peptides into robust collagen mimetic bioscaffolds for aging skin rejuvenation.
    Linyan Yao, Biyang Ling, Wenjie Huang, Qi Wang, Xiangdong Cai, Jianxi Xiao.
      Skin aging, a complex physiological process characterized by alterations in skin structure and function, seriously affects human life. Collagen holds considerable potential in aging skin treatment, while animal-derived collagen poses risks of pathogen transmission. Self-assembled peptides have garnered increasing attention in creating collagen mimetic materials; however, previous reported self-assembled peptides rely on vulnerable non-covalent interactions or lack the capability of controlling morphology and incorporating functional motifs, limiting their ability to mimic collagen structure and function. We have herein created a controllable tyrosine-rich triblock peptide system capable of self-assembling into robust collagen mimetic bioscaffolds for rejuvenating aging skin. Through ruthenium-mediated crosslinking, these peptides self-assemble into well-defined nanospheres or collagen-mimetic scaffolds, precisely regulated by the triple-helical structure and tyrosine distribution. The self-assembled collagen mimetic scaffolds exhibit outstanding resistances to various solvents and pH conditions. The integrin-binding motif has been incorporated into the triple helical block without disrupting their assembly, while endowing them with superior bioactivities, effectively promoting cell adhesion and proliferation. In vivo studies demonstrated their efficacy in treating photoaging skin by accelerating collagen regeneration and activating fibroblasts. The self-assembled tyrosine-rich triblock peptides represent a versatile system for creating robust collagen mimetic biomaterials, providing great potential in skin rejuvenation and tissue regeneration.
    Keywords:  collagen mimetic bioscaffolds; skin rejuvenation; tyrosine-rich peptides
    DOI:  https://doi.org/10.1093/rb/rbae085
  33. Adv Wound Care (New Rochelle). 2024 Aug 22.
    Biosponge-Encased Placental Stem Cells for Volumetric Muscle Loss Repair.
    David Johnson, Mia Ridolfo, Ryan Mueller, Megan Chermack, Julia Brockhouse, Jamshid Tadiwala, Avantika Jain, Kenneth Bertram, Koyal Garg.
      OBJECTIVE: Volumetric muscle loss (VML) leads to permanent muscle mass and functional impairments. While mesenchymal stromal cells (MSCs) and their secreted factors can aid muscle regeneration, MSCs exhibit limited persistence in injured tissue post-transplantation. Human placenta-derived stem cells (hPDSCs), sharing surface markers with MSCs, demonstrate superior regenerative potential due to their fetal origin. Previously, a biosponge (BS) scaffold was shown to augment muscle regeneration post-VML. This study aims to co-apply BS therapy and hPDSCs to further enhance muscle recovery following VML.APPROACH: A VML defect was created by removing ~20% of the tibialis anterior muscle mass in male Lewis rats. Injured muscles were either left untreated or treated with BS or BS-encapsulated hPDSCs cultured under normoxic or hypoxic conditions. On day 28 post-injury, peak isometric torque was measured, and the muscle was harvested for analysis.
    RESULTS: BS encapsulated hPDSCs subjected to hypoxic preconditioning persisted in larger quantities and enhanced muscle mass at day 28 post-injury. BS encapsulated hPDSCs cultured under normoxic or hypoxic conditions increased small myofibers (<500 µm2) percentage, MyoD protein expression, and both pro- and anti-inflammatory macrophage marker expression. BS encapsulated hPDSCs also reduced fibrosis and BS remodeling rate.
    INNOVATION: This study is the first to examine the therapeutic effects of hPDSCs in a rat VML model. A BS carrier and hypoxic preconditioning were investigated to mitigate low cell survival post-implantation.
    CONCLUSION: hPDSCs augment the regenerative effect of BS. Combining hPDSCs and BS emerges as a promising strategy worthy of further investigation.
    DOI:  https://doi.org/10.1089/wound.2024.0077
  34. Bone Res. 2024 Aug 21. 12(1): 45
    Rejuvenation of BMSCs senescence by pharmacological enhancement of TFEB-mediated autophagy alleviates aged-related bone loss and extends lifespan in middle aged mice.
    Ziwei Luo, Wanyi Wei, Dawei Qiu, Zixia Su, Liangpu Liu, Honghai Zhou, Hao Cui, Li Yang.
      Bone marrow stromal/stem cells (BMSCs) are generally considered as common progenitors for both osteoblasts and adipocytes in the bone marrow, but show preferential differentiation into adipocytes rather than osteoblasts under aging, thus leading to senile osteoporosis. Accumulated evidences indicate that rejuvenation of BMSCs by autophagic enhancement delays bone aging. Here we synthetized and demonstrated a novel autophagy activator, CXM102 that could induce autophagy in aged BMSCs, resulting in rejuvenation and preferential differentiation into osteoblasts of BMSCs. Furthermore, CXM102 significantly stimulated bone anabolism, reduced marrow adipocytes, and delayed bone loss in middle-age male mice. Mechanistically, CXM102 promoted transcription factor EB (TFEB) nuclear translocation and favored osteoblasts formation both in vitro and in vivo. Moreover, CXM102 decreased serum levels of inflammation and reduced organ fibrosis, leading to a prolonger lifespan in male mice. Our results indicated that CXM102 could be used as an autophagy inducer to rejuvenate BMSCs and shed new lights on strategies for senile osteoporosis and healthyspan improvement.
    DOI:  https://doi.org/10.1038/s41413-024-00351-7
  35. Mol Ther. 2024 Aug 20. pii: S1525-0016(24)00539-2. [Epub ahead of print]
    On RNA-programmable gene modulation as a versatile set of principles targeting muscular dystrophies.
    Sabrina Capelletti, Sofía C García Soto, Manuel A F V Gonçalves.
      The repurposing of RNA-programmable CRISPR systems from genome editing into epigenome editing tools is gaining pace, including in research and development efforts directed at tackling human disorders. This momentum stems from the increasing knowledge regarding the epigenetic factors and networks underlying cell physiology and disease aetiology and from the growing realization that genome editing principles involving chromosomal breaks generated by programmable nucleases are prone to unpredictable genetic changes and outcomes. Hence, engineered CRISPR systems are serving as versatile DNA-targeting scaffolds for synthetic effector domains that, via locally recruiting transcription factors and chromatin remodelling complexes, seek interfering with loss-of-function and gain-of-function processes underlying recessive and dominant disorders, respectively. Here, after providing an overview about epigenetic drugs and CRISPR-Cas9-based activation and interference platforms, we cover the testing of these systems in the context of molecular therapies for muscular dystrophies. Finally, we examine attributes, obstacles and deployment opportunities for CRISPR-based epigenetic modulating technologies.
    DOI:  https://doi.org/10.1016/j.ymthe.2024.08.016
  36. Cancer Sci. 2024 Aug 18.
    A highly sensitive reporter system to monitor endogenous YAP1/TAZ activity and its application in various human cells.
    Hiroki Hikasa, Kohichi Kawahara, Masako Inui, Yukichika Yasuki, Keita Yamashita, Kohei Otsubo, Shojiro Kitajima, Miki Nishio, Kazunari Arima, Motoyoshi Endo, Masanori Taira, Akira Suzuki.
      The activation of yes-associated protein 1 (YAP1) and transcriptional co-activator with PDZ-binding motif (TAZ) has been implicated in both regeneration and tumorigenesis, thus representing a double-edged sword in tissue homeostasis. However, how the activity of YAP1/TAZ is regulated or what leads to its dysregulation in these processes remains unknown. To explore the upstream stimuli modulating the cellular activity of YAP1/TAZ, we developed a highly sensitive YAP1/TAZ/TEAD-responsive DNA element (YRE) and incorporated it into a lentivirus-based reporter cell system to allow for sensitive and specific monitoring of the endogenous activity of YAP1/TAZ in terms of luciferase activity in vitro and Venus fluorescence in vivo. Furthermore, by replacing YRE with TCF- and NF-κB-binding DNA elements, we demonstrated the applicability of this reporter system to other pathways such as Wnt/β-catenin/TCF- and IL-1β/NF-κB-mediated signaling, respectively. The practicality of this system was evaluated by performing cell-based reporter screening of a chemical compound library consisting of 364 known inhibitors, using reporter-introduced cells capable of quantifying YAP1/TAZ- and β-catenin-mediated transcription activities, which led to the identification of multiple inhibitors, including previously known as well as novel modulators of these signaling pathways. We further confirmed that novel YAP1/TAZ modulators, such as potassium ionophores, Janus kinase inhibitors, platelet-derived growth factor receptor inhibitors, and genotoxic stress inducers, alter the protein level or phosphorylation of endogenous YAP1/TAZ and the expression of their target genes. Thus, this reporter system provides a powerful tool to monitor endogenous signaling activities of interest (even in living cells) and search for modulators in various cellular contexts.
    Keywords:  Hippo‐YAP1/TAZ pathway; YAP1/TAZ modulators; cell‐based screening; highly sensitive reporter system; lentivirus
    DOI:  https://doi.org/10.1111/cas.16316
  37. Aging Cell. 2024 Aug 18. e14316
    Cooperative nuclear action of RNA-binding proteins PSF and G3BP2 to sustain neuronal cell viability is decreased in aging and dementia.
    Ken-Ichi Takayama, Takashi Suzuki, Kaoru Sato, Yuko Saito, Satoshi Inoue.
      Dysfunctional RNA-binding proteins (RBPs) have been implicated in several geriatric diseases, including Alzheimer's disease (AD). However, little is known about the nuclear molecular actions and cooperative functions mediated by RBPs that affect gene regulation in sporadic AD or aging. In the present study, we investigated aging- and AD-associated changes in the expression of PSF and G3BP2, which are representative RBPs associated with sex hormone activity. We determined that both PSF and G3BP2 levels were decreased in aged brains compared to young brains of mice. RNA sequencing (RNA-seq) analysis of human neuronal cells has shown that PSF is responsible for neuron-specific functions and sustains cell viability. In addition, we showed that PSF interacted with G3BP2 in the nucleus and stress granules (SGs) at the protein level. Moreover, PSF-mediated gene regulation at the RNA level correlated with G3BP2. Interestingly, PSF and G3BP2 target genes are associated with AD development. Mechanistically, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis demonstrated that the interaction of RBPs with the pre-mRNA of target genes enhanced post-transcriptional mRNA stability, suggesting a possible role for these RBPs in preserving neuronal cell viability. Notably, in the brains of patients with sporadic AD, decreased expression of PSF and G3BP2 in neurons was observed compared to non-AD patients. Overall, our findings suggest that the cooperative action of PSF and G3BP2 in the nucleus is important for preventing aging and AD development.
    Keywords:  Alzheimer type of dementia; RNA‐binding protein; aging; androgen; estrogen; paraspeckle; stress granule
    DOI:  https://doi.org/10.1111/acel.14316
  38. Theriogenology. 2024 Aug 10. pii: S0093-691X(24)00330-3. [Epub ahead of print]229 66-74
    FOXM1 affects oxidative stress, mitochondrial function, and the DNA damage response by regulating p21 in aging oocytes.
    Wenjie Yu, Xiaoshi Cai, Chen Wang, Xinyue Peng, Lingxia Xu, Yan Gao, Tian Tian, Guangying Zhu, Yuan Pan, Hongzhong Chu, Shuang Liang, Chengzhen Chen, Nam-Hyung Kim, Bao Yuan, Jiabao Zhang, Hao Jiang.
      Fertilization capacity and embryo survival rate are decreased in postovulatory aging oocytes, which results in a reduced reproductive rate in female animals. However, the key regulatory genes and related regulatory mechanisms involved in the process of postovulatory aging in oocytes remain unclear. In this study, RNA-Seq revealed that 3237 genes were differentially expressed in porcine oocytes between the MII and aging stages (MII + 24 h). The expression level of FOXM1 was increased at the aging stage, and FOXM1 was also observed to be enriched in many key biological processes, such as cell senescence, response to oxidative stress, and transcription, during porcine oocyte aging. Previous studies have shown that FOXM1 is involved in the regulation of various biological processes, such as oxidative stress, DNA damage repair, mitochondrial function, and cellular senescence, which suggests that FOXM1 may play a crucial role in the process of postovulatory aging. Therefore, in this study, we investigated the effects and mechanisms of FOXM1 on oxidative stress, mitochondrial function, DNA damage, and apoptosis during oocyte aging. Our study revealed that aging oocytes exhibited significantly increased ROS levels and significantly decreased GSH, SOD, T-AOC, and CAT levels than did oocytes at the MII stage and that FOXM1 inhibition exacerbated the changes in these levels in aging oocytes. In addition, FOXM1 inhibition increased the levels of DNA damage, apoptosis, and cell senescence in aging oocytes. A p21 inhibitor alleviated the effects of FOXM1 inhibition on oxidative stress, mitochondrial function, and DNA damage and thus alleviated the degree of senescence in aging oocytes. These results indicate that FOXM1 plays a crucial role in porcine oocyte aging. This study contributes to the understanding of the function and mechanism of FOXM1 during porcine oocyte aging and provides a theoretical basis for preventing oocyte aging and optimizing conditions for the in vitro culture of oocytes.
    Keywords:  FOXM1; Pig; Postovulatory aging; p21
    DOI:  https://doi.org/10.1016/j.theriogenology.2024.08.010
  39. Gene. 2024 Aug 17. pii: S0378-1119(24)00754-6. [Epub ahead of print]931 148873
    Sarcopenia is attenuated by mairin in SAMP8 mice via the inhibition of FAPs fibrosis through the AMPK-TGF-β-SMAD axis.
    Wen Zhong, Huanan Jia, Haiyan Zhu, Yuan Tian, Wei Huang, Qiyue Yang.
      Sarcopenia has become a prominent health problem among the elderly because of its adverse consequence, including physical disabilities and death. Fibro-adipogenic progenitors (FAPs) exhibit adipogenic and fibrogenic potencies and regulate skeletal muscle development, which plays important role in sarcopenia. Mairin, as an ingredient of Astragalus membranaceus, has the effect of anti-fibrosis. Therefore, we predicted that mairin targeted the fibrosis of FAPs and then affected sarcopenia. To verify our ideas, mairin (30 mg/kg/day or 60 mg/kg/day) was given to senescence accelerated mouse-prone 8 (SAMP8) mice by oral administration. Aging led to loss of weight, skeletal muscle mass, strength, and function, and an increase in muscle atrophy and fibrosis, while mairin administration inhibited physiological decline caused by aging. Similarly, mairin (20 μM or 40 μM) treatment enhanced FAP proliferation but blocked the differentiation into fibroblasts. Mechanically, mairin played an anti-fibrotic role via AMP-activated protein kinase-transforming growth factor beta-drosophila mothers against decapentaplegic protein (AMPK-TGF-β-SMAD) axis, as evidenced by increased phosphorylation of AMPKα and decreased TGF-β and phosphorylated-SMAD2/3. In addition, the potential target genes of mairin were explored by mRNA sequencing in our study. In conclusion, mairin may interfere with the AMPK/TGF-β/SMAD pathway to repress the fibrosis of FAPs and eventually ameliorate sarcopenia.
    Keywords:  AMPK-TGF-β-SMAD; FAPs; Fibrosis; Mairin; Sarcopenia
    DOI:  https://doi.org/10.1016/j.gene.2024.148873
  40. Cell Syst. 2024 Aug 21. pii: S2405-4712(24)00206-0. [Epub ahead of print]15(8): 738-752.e5
    Enhanced cellular longevity arising from environmental fluctuations.
    Yuting Liu, Zhen Zhou, Hetian Su, Songlin Wu, Gavin Ni, Alex Zhang, Lev S Tsimring, Jeff Hasty, Nan Hao.
      Cellular longevity is regulated by both genetic and environmental factors. However, the interactions of these factors in the context of aging remain largely unclear. Here, we formulate a mathematical model for dynamic glucose modulation of a core gene circuit in yeast aging, which not only guided the design of pro-longevity interventions but also revealed the theoretical principles underlying these interventions. We introduce the dynamical systems theory to capture two general means for promoting longevity-the creation of a stable fixed point in the "healthy" state of the cell and the "dynamic stabilization" of the system around this healthy state through environmental oscillations. Guided by the model, we investigate how both of these can be experimentally realized by dynamically modulating environmental glucose levels. The results establish a paradigm for theoretically analyzing the trajectories and perturbations of aging that can be generalized to aging processes in diverse cell types and organisms.
    Keywords:  aging; caloric restriction; computational modeling; dynamical systems theory; longevity; metabolism; quantitative biology; single-cell imaging; systems biology; time-lapse microscopy
    DOI:  https://doi.org/10.1016/j.cels.2024.07.007
  41. Mol Nutr Food Res. 2024 Aug 20. e2400297
    Ethanol Extract of Propolis Attenuates Liver Lipid Metabolism Disorder in High-Fat Diet-Fed SAMP8 Mice.
    Quan-Yuan Xie, Xin Shu, Tao Liu, Li-Li Chen, Li-Ping Luo.
      SCOPE: The prevalence of high-fat diet (HFD) consumption is increasing among middle-aged and older adults, which accelerates the aging process of this population and is more likely to induce lipid metabolism disorders. But the alleviation of ethanolic extract of propolis (EEP) on lipid metabolism disorders during aging remains unclear.METHODS AND RESULTS: This study assesseed the impact of EEP intervention (200 mg kg-1 bw) on aging and lipid metabolism disorders in HFD-fed senescence accelerate mouse prone 8 (SAMP8) mice. Findings indicate that EEP ameliorates hair luster degradation and weight gain, reduces systemic inflammation and metabolism levels, enhances hepatic antioxidant enzyme activities, and improves the hepatic expression of senescence-associated secretory phenotype and aging-related genes in HFD-fed SAMP8 mice. Histological staining demonstrates that EEP improves hepatic lipid deposition and inflammatory cell infiltration. Transcriptomic and lipidomic analysis reveal that EEP promotes fatty acid β-oxidation by activating PPAR pathway, resulting in reduced hepatic lipid deposition, and attenuates bile acid (BA) accumulation by improving BA metabolism, which were ensured through qPCR validation of key genes and immunoblot validation of key proteins. CONCLUSIONS : EEP can regulate lipid metabolic dysregulation during aging accompanied by an HFD, potentially delaying the onset and progression of age-related diseases. This provides new approach for supporting healthy aging.
    Keywords:  SAMP8 mice; high‐fat diet; lipid metabolism disorder; propolis; transcriptomic and lipidomic
    DOI:  https://doi.org/10.1002/mnfr.202400297
  42. MedComm (2020). 2024 Sep;5(9): e645
    Current developments of gene therapy in human diseases.
    Fanfei Liu, Ruiting Li, Zilin Zhu, Yang Yang, Fang Lu.
      Gene therapy has witnessed substantial advancements in recent years, becoming a constructive tactic for treating various human diseases. This review presents a comprehensive overview of these developments, with a focus on their diverse applications in different disease contexts. It explores the evolution of gene delivery systems, encompassing viral (like adeno-associated virus; AAV) and nonviral approaches, and evaluates their inherent strengths and limitations. Moreover, the review delves into the progress made in targeting specific tissues and cell types, spanning the eye, liver, muscles, and central nervous system, among others, using these gene technologies. This targeted approach is crucial in addressing a broad spectrum of genetic disorders, such as inherited lysosomal storage diseases, neurodegenerative disorders, and cardiovascular diseases. Recent clinical trials and successful outcomes in gene therapy, particularly those involving AAV and the clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated proteins, are highlighted, illuminating the transformative potentials of this approach in disease treatment. The review summarizes the current status of gene therapy, its prospects, and its capacity to significantly ameliorate patient outcomes and quality of life. By offering comprehensive analysis, this review provides invaluable insights for researchers, clinicians, and stakeholders, enriching the ongoing discourse on the trajectory of disease treatment.
    Keywords:  AAV; CRISPR–Cas; clinical trials; gene therapy; human diseases
    DOI:  https://doi.org/10.1002/mco2.645
  43. Biogerontology. 2024 Aug 23.
    Caloric restriction mimetics improve gut microbiota: a promising neurotherapeutics approach for managing age-related neurodegenerative disorders.
    Ishika Singh, Shashi Anand, Deepashree J Gowda, Amitha Kamath, Abhishek Kumar Singh.
      The gut microbiota (GM) produces various molecules that regulate the physiological functionality of the brain through the gut-brain axis (GBA). Studies suggest that alteration in GBA may lead to the onset and progression of various neurological dysfunctions. Moreover, aging is one of the prominent causes that contribute to the alteration of GBA. With age, GM undergoes a shift in population size and species of microflora leading to changes in their secreted metabolites. These changes also hamper communications among the HPA (hypothalamic-pituitary-adrenal), ENS (enteric nervous system), and ANS (autonomic nervous system). A therapeutic intervention that has recently gained attention in improving health and maintaining communication between the gut and the brain is calorie restriction (CR), which also plays a critical role in autophagy and neurogenesis processes. However, its strict regime and lifelong commitment pose challenges. The need is to produce similar beneficial effects of CR without having its rigorous compliance. This led to an exploration of calorie restriction mimetics (CRMs) which could mimic CR's functions without limiting diet, providing long-term health benefits. CRMs ensure the efficient functioning of the GBA through gut bacteria and their metabolites i.e., short-chain fatty acids, bile acids, and neurotransmitters. This is particularly beneficial for elderly individuals, as the GM deteriorates with age and the body's ability to digest the toxic accumulates declines. In this review, we have explored the beneficial effect of CRMs in extending lifespan by enhancing the beneficial bacteria and their effects on metabolite production, physiological conditions, and neurological dysfunctions including neurodegenerative disorders.
    Keywords:  Aging; Caloric restriction mimetics; Gut microbiota; Gut-brain axis; Neurodegenerative disorders
    DOI:  https://doi.org/10.1007/s10522-024-10128-4
  44. Skin Res Technol. 2024 Aug;30(8): e13918
    Adipose-derived stem cells transplantation improves survival and alleviates contraction of skin grafts via promoting macrophages M2 polarization.
    Yuying Cui, Jiahao He, Zheyuan Yu, Sizheng Zhou, Dejun Cao, Taoran Jiang, Bin Fang, Guangshuai Li.
      BACKGROUND: Full-thickness skin grafts are widely used in plastic and reconstructive surgery. The main limitation of skin grafting is the poor textural durability and associated contracture, which often needs further corrective surgery. Excessive inflammation is the main reason for skin graft contractions, which involve overactivation of myofibroblasts. These problems have prompted the development of new therapeutic approaches, including macrophage polarization modulation and stem cell-based therapies. Currently, adipose-derived stem cells (ASCs) have shown promise in promoting skin grafts survival and regulating macrophage phenotypes. However, the roles of ASCs on macrophages in decreasing skin grafts contraction remain unknown.MATERIALS AND METHODS: Rat adipose-derived stem cells (rASCs) were isolated from rat inguinal adipose tissues. Full-thickness skin graft model was constructed on male rats divided into control group and rASCs treatment group. Skin graft was assessed for concentration, elasticity modulus and stiffness. Rat bone marrow-derived macrophages (rBMDMs) were isolated from rat femurs, and subsequent RT-qPCR and coculture assays were carried out to explore the cellular mechanisms. Immunohistochemical and immunofluorescence staining were used to verify mechanisms in vivo.
    RESULTS: In vivo results showed that after injection of ASCs, improved texture, increased survival and inhibited contraction of skin grafts were seen. Vascularization was also improved as illustrated by laser perfusion image and vascular endothelial growth factor (VEGF) concentration. Histological analysis revealed that ASCs injection significantly reduced expression of pro-inflammatory cytokines (TNF-a, IL-1β) and increased expression of anti-inflammatory (IL-10) and pro-healing cytokines (IGF-1). At cellular level, after co-culturing with rASCs, rat bone marrow derived macrophages (rBMDMs) favored M2 polarization even under inflammatory stimulus.
    CONCLUSION: ASCs treatment enhanced vascularization via angiogenic cytokines secretion and alleviated inflammatory environment in skin grafts by driving M2 macrophages polarization, which improved survival and decreased skin grafts contraction. Our work showed that ASCs transplantation can be harnessed to enhance therapeutic efficacy of skin grafting in cutaneous defects treatment.
    Keywords:  adipose‐derived stem cells; full‐thickness skin grafts; macrophage polarization; skin grafts contraction; skin grafts survival
    DOI:  https://doi.org/10.1111/srt.13918
  45. Sci Rep. 2024 08 22. 14(1): 19546
    Mitigation of aging-related plasticity decline through taurine supplementation and environmental enrichment.
    Aleksandra Gawryluk, Anita Cybulska-Klosowicz, Agata Charzynska, Renata Zakrzewska, Alicja Sobolewska, Malgorzata Kossut, Monika Liguz-Lecznar.
      Aging-related biochemical changes in nerve cells lead to dysfunctional synapses and disrupted neuronal circuits, ultimately affecting vital processes such as brain plasticity, learning, and memory. The imbalance between excitation and inhibition in synaptic function during aging contributes to cognitive impairment, emphasizing the importance of compensatory mechanisms. Fear conditioning-related plasticity of the somatosensory barrel cortex, relying on the proper functioning and extensive up regulation of the GABAergic system, in particular interneurons containing somatostatin, is compromised in aging (one-year-old) mice. The present research explores two potential interventions, taurine supplementation, and environmental enrichment, revealing their effectiveness in supporting learning-induced plasticity in the aging mouse brain. They do not act through a mechanism normalizing the Glutamate/GABA balance that is disrupted in aging. Still, they allow for increased somatostatin levels, an effect observed in young animals after learning. These findings highlight the potential of lifestyle interventions and diet supplementation to mitigate age-related cognitive decline by promoting experience-dependent plasticity.
    DOI:  https://doi.org/10.1038/s41598-024-70261-5
  46. Pharmacol Res. 2024 Aug 17. pii: S1043-6618(24)00306-2. [Epub ahead of print] 107361
    Gut microbiota-brain bile acid axis orchestrates aging-related neuroinflammation and behavior impairment in mice.
    Junli Ma, Mingxiao Li, Yiyang Bao, Wenjin Huang, Xiaofang He, Ying Hong, Wenjing Wei, Zekun Liu, Xinxin Gao, Yang Yang, Zhengyu Cui, Wantao Wang, Jie Wang, Weize Zhu, Ningning Zheng, Lingyun Pan, Deheng Wang, Zunji Ke, Ben Zhou, Lili Sheng, Houkai Li.
      Emerging evidence shows that disrupted gut microbiota-bile acid (BA) axis is critically involved in the development of neurodegenerative diseases. However, the alterations in spatial distribution of BAs among different brain regions that command important functions during aging and their exact roles in aging-related neurodegenerative diseases are poorly understood. Here, we analyzed the BA profiles in cerebral cortex, hippocampus, and hypothalamus of young and natural aging mice of both sexes. The results showed that aging altered brain BA profiles sex- and region- dependently, in which TβMCA was consistently elevated in aging mice of both sexes, particularly in the hippocampus and hypothalamus. Furthermore, we found that aging accumulated-TβMCA stimulated microglia inflammation in vitro and shortened the lifespan of C. elegans, as well as behavioral impairment and neuroinflammation in mice. In addition, metagenomic analysis suggested that the accumulation of brain TβMCA during aging was partially attributed to reduction in BSH-carrying bacteria. Finally, rejuvenation of gut microbiota by co-housing aged mice with young mice restored brain BA homeostasis and improved neurological dysfunctions in natural aging mice. In conclusion, our current study highlighted the potential of improving aging-related neuro-impairment by targeting gut microbiota-brain BA axis.
    Keywords:  aging; bile acid; brain; gut microbiota; neuro-impairment
    DOI:  https://doi.org/10.1016/j.phrs.2024.107361
  47. Dev Cell. 2024 Aug 17. pii: S1534-5807(24)00482-9. [Epub ahead of print]
    A single-cell transcriptomic census of mammalian olfactory epithelium aging.
    Weihao Li, Tingting Wu, Kesen Zhu, Guangyi Ba, Jinxia Liu, Ping Zhou, Shengjv Li, Li Wang, Huanhai Liu, Wenwen Ren, Hongmeng Yu, Yiqun Yu.
      Mammalian olfactory epithelium has the capacity of self-renewal throughout life. Aging is one of the major causes leading to the olfactory dysfunction. Here, we performed single-cell RNA sequencing (scRNA-seq) analysis on young and aged murine olfactory epithelium (OE) and identified aging-related differentially expressed genes (DEGs) throughout 21 cell types. Aging led to the presence of activated horizontal basal cells (HBCs) in the OE and promoted cellular interaction between HBCs and neutrophils. Aging enhanced the expression of Egr1 and Fos in sustentacular cell differentiation from multipotent progenitors, whereas Bcl11b was downregulated during the sensory neuronal homeostasis in the aged OE. Egr1 and Cebpb were predictive core regulatory factors of the transcriptional network in the OE. Overexpression of Egr1 in aged OE organoids promoted cell proliferation and neuronal differentiation. Moreover, aging altered expression levels and frequencies of olfactory receptors. These findings provide a cellular and molecular framework of OE aging at the single-cell resolution.
    Keywords:  aging; horizontal basal cell; olfactory epithelium; olfactory receptor; olfactory sensory neuron; single-cell RNA sequencing
    DOI:  https://doi.org/10.1016/j.devcel.2024.07.020
  48. J Cachexia Sarcopenia Muscle. 2024 Aug 18.
    Higher serum uric acid as a risk factor for frailty in older adults: A nationwide population-based study.
    Min-Gu Kang, Ji Yeon Baek, Yunju Jo, Dongryeol Ryu, Il-Young Jang, Hee-Won Jung, Beom-Jun Kim.
      BACKGROUND: Uric acid (UA), the terminal breakdown product of purine metabolism, possesses contradictory roles, functioning both as an inflammatory mediator and as an antioxidant. Its clinical relevance, particularly in geriatric populations, remains a topic of ongoing debate. Aiming to elucidate whether circulating UA is detrimental or beneficial to human health, we investigate the association between serum UA concentrations and the frailty index-a comprehensive measure of biological aging in a nationally representative cohort of community-dwelling older adults.METHODS: We conducted a population-based, cross-sectional study utilizing data from the Korea National Health and Nutrition Examination Survey. The sample included 4268 participants aged 65 years and above. A deficit accumulation frailty index (FI) was constructed using 38 items that assess physical, cognitive, psychological, and social domains. Based on the FI, participants were categorized into non-frail (FI ≤ 0.15), pre-frail (0.15 < FI ≤ 0.25), or frail (FI > 0.25). Serum UA levels were quantified through a colorimetric enzymatic assay.
    RESULTS: After controlling for confounders such as age, sex, socioeconomic status (including income and education level), lifestyle factors (smoking status), and medical history (hypertension, diabetes, dyslipidemia, stroke, cardiovascular diseases), and body mass index, serum UA levels were observed to be significantly higher in frail participants compared with their non-frail counterparts (P < 0.001). Furthermore, serum UA concentrations demonstrated a positive correlation with the FI (P < 0.001), and the odds ratio for frailty per 1 mg/dL increase in serum UA was 1.22 (P < 0.001). Additionally, older adults in the highest quartile of UA levels exhibited a significantly higher FI and 1.66-fold increased odds of frailty compared with those in the lowest quartile (P = 0.011 and P = 0.005, respectively).
    CONCLUSIONS: These findings suggest that elevated circulating UA levels may act as a pro-aging factor rather than an anti-aging one in older adults, highlighting its potential role in accelerating biological aging. The data further support the utility of serum UA as a potential blood-based biomarker for frailty in this demographic, contributing to the expanding evidence on its significance in geriatric health assessments.
    Keywords:  Frailty index; Oxidative stress; Pro‐aging factor; Systemic inflammation; Uric acid
    DOI:  https://doi.org/10.1002/jcsm.13561
  49. Transgenic Res. 2024 Aug 19.
    Next-generation CRISPR technology for genome, epigenome and mitochondrial editing.
    Cia-Hin Lau, Qing-Le Liang, Haibao Zhu.
      The application of rapidly growing CRISPR toolboxes and methods has great potential to transform biomedical research. Here, we provide a snapshot of up-to-date CRISPR toolboxes, then critically discuss the promises and hurdles associated with CRISPR-based nuclear genome editing, epigenome editing, and mitochondrial editing. The technical challenges and key solutions to realize epigenome editing in vivo, in vivo base editing and prime editing, mitochondrial editing in complex tissues and animals, and CRISPR-associated transposases and integrases in targeted genomic integration of very large DNA payloads are discussed. Lastly, we discuss the latest situation of the CRISPR/Cas9 clinical trials and provide perspectives on CRISPR-based gene therapy. Apart from technical shortcomings, ethical and societal considerations for CRISPR applications in human therapeutics and research are extensively highlighted.
    Keywords:  Base editor; CRISPR; Epigenome editing; Genome editing; Integrase; Mitochondrial editing; Prime editor; Transposase
    DOI:  https://doi.org/10.1007/s11248-024-00404-x
  50. Plant J. 2024 Aug 17.
    Using AlphaFold Multimer to discover interkingdom protein-protein interactions.
    Felix Homma, Joy Lyu, Renier A L van der Hoorn.
      Structural prediction by artificial intelligence can be powerful new instruments to discover novel protein-protein interactions, but the community still grapples with the implementation, opportunities and limitations. Here, we discuss and re-analyse our in silico screen for novel pathogen-secreted inhibitors of immune hydrolases to illustrate the power and limitations of structural predictions. We discuss strategies of curating sequences, including controls, and reusing sequence alignments and highlight important limitations caused by different platforms, sequence depth and computing times. We hope these experiences will support similar interactomic screens by the research community.
    Keywords:  AlphaFold Multimer; artificial intelligence; computing cluster; hydrolase; inhibitor; protein folding; small secreted protein
    DOI:  https://doi.org/10.1111/tpj.16969
  51. Front Aging Neurosci. 2024 ;16 1428244
    Neural ageing and synaptic plasticity: prioritizing brain health in healthy longevity.
    Sheeja Navakkode, Brian K Kennedy.
      Ageing is characterized by a gradual decline in the efficiency of physiological functions and increased vulnerability to diseases. Ageing affects the entire body, including physical, mental, and social well-being, but its impact on the brain and cognition can have a particularly significant effect on an individual's overall quality of life. Therefore, enhancing lifespan and physical health in longevity studies will be incomplete if cognitive ageing is over looked. Promoting successful cognitive ageing encompasses the objectives of mitigating cognitive decline, as well as simultaneously enhancing brain function and cognitive reserve. Studies in both humans and animal models indicate that cognitive decline related to normal ageing and age-associated brain disorders are more likely linked to changes in synaptic connections that form the basis of learning and memory. This activity-dependent synaptic plasticity reorganises the structure and function of neurons not only to adapt to new environments, but also to remain robust and stable over time. Therefore, understanding the neural mechanisms that are responsible for age-related cognitive decline becomes increasingly important. In this review, we explore the multifaceted aspects of healthy brain ageing with emphasis on synaptic plasticity, its adaptive mechanisms and the various factors affecting the decline in cognitive functions during ageing. We will also explore the dynamic brain and neuroplasticity, and the role of lifestyle in shaping neuronal plasticity.
    Keywords:  calcium; cognitive ageing; healthy ageing; hippocampus; long-term potentiation; longevity; neuroinflammation; synaptic plasticity
    DOI:  https://doi.org/10.3389/fnagi.2024.1428244
  52. Proc Natl Acad Sci U S A. 2024 Aug 27. 121(35): e2406787121
    Hydrogel biomaterials that stiffen and soften on demand reveal that skeletal muscle stem cells harbor a mechanical memory.
    Christopher M Madl, Yu Xin Wang, Colin A Holbrook, Shiqi Su, Xuechen Shi, Fitzroy J Byfield, Gwendoline Wicki, Iris A Flaig, Helen M Blau.
      Muscle stem cells (MuSCs) are specialized cells that reside in adult skeletal muscle poised to repair muscle tissue. The ability of MuSCs to regenerate damaged tissues declines markedly with aging and in diseases such as Duchenne muscular dystrophy, but the underlying causes of MuSC dysfunction remain poorly understood. Both aging and disease result in dramatic increases in the stiffness of the muscle tissue microenvironment from fibrosis. MuSCs are known to lose their regenerative potential if cultured on stiff plastic substrates. We sought to determine whether MuSCs harbor a memory of their past microenvironment and if it can be overcome. We tested MuSCs in situ using dynamic hydrogel biomaterials that soften or stiffen on demand in response to light and found that freshly isolated MuSCs develop a persistent memory of substrate stiffness characterized by loss of proliferative progenitors within the first three days of culture on stiff substrates. MuSCs cultured on soft hydrogels had altered cytoskeletal organization and activity of Rho and Rac guanosine triphosphate hydrolase (GTPase) and Yes-associated protein mechanotransduction pathways compared to those on stiff hydrogels. Pharmacologic inhibition identified RhoA activation as responsible for the mechanical memory phenotype, and single-cell RNA sequencing revealed a molecular signature of the mechanical memory. These studies highlight that microenvironmental stiffness regulates MuSC fate and leads to MuSC dysfunction that is not readily reversed by changing stiffness. Our results suggest that stiffness can be circumvented by targeting downstream signaling pathways to overcome stem cell dysfunction in aged and disease states with aberrant fibrotic tissue mechanics.
    Keywords:  dynamic hydrogels; fibrosis; mechanical memory; mechanotransduction; muscle stem cells
    DOI:  https://doi.org/10.1073/pnas.2406787121
  53. Cell Rep. 2024 Aug 20. pii: S2211-1247(24)01014-3. [Epub ahead of print]43(9): 114663
    Non-canonical metabolic and molecular effects of calorie restriction are revealed by varying temporal conditions.
    Heidi H Pak, Allison N Grossberg, Rachel R Sanderfoot, Reji Babygirija, Cara L Green, Mikaela Koller, Monika Dzieciatkowska, Daniel A Paredes, Dudley W Lamming.
      Calorie restriction (CR) extends lifespan and healthspan in diverse species. Comparing ad libitum- and CR-fed mice is challenging due to their significantly different feeding patterns, with CR-fed mice consuming their daily meal in 2 h and then subjecting themselves to a prolonged daily fast. Here, we examine how ad libitum- and CR-fed mice respond to tests performed at various times and fasting durations and find that the effects of CR-insulin sensitivity, circulating metabolite levels, and mechanistic target of rapamycin 1 (mTORC1) activity-result from the specific temporal conditions chosen, with CR-induced improvements in insulin sensitivity observed only after a prolonged fast, and the observed differences in mTORC1 activity between ad libitum- and CR-fed mice dependent upon both fasting duration and the specific tissue examined. Our results demonstrate that much of our understanding of the effects of CR are related to when, relative to feeding, we choose to examine the mice.
    Keywords:  CP: Metabolism; aging; calorie restriction; dietary restriction; fasting; lifespan; mTOR; time-restricted feeding
    DOI:  https://doi.org/10.1016/j.celrep.2024.114663
  54. Syst Biol Reprod Med. 2024 Dec;70(1): 249-260
    Transcriptome analyses reveal key features of mouse seminal vesicle during aging.
    Peng Luo, Haibin Guo, Baoning Liu, Zhiqiang Zhang, Yun Xie, Jiahui Yao, Xiangping Li, Jun Bian, Jintao Zhuang, Bin Ouyang, Jinhua Wu.
      Despite the significant morphological changes that occur in the seminal vesicles with aging, the transcriptomic characteristics remain largely unexplored. To address this, we performed bulk RNA sequencing on seminal vesicle samples from mice aged 3, 13, and 21 months to uncover transcriptomic alterations. Our findings reveal that aged seminal vesicles display cystic dilatation, epithelial hypoplasia, disordered muscle layers, fibrosis, and reduced proliferation capability. A comparison between 3-month-old and 21-month-old mice indicated that leukocyte-mediated immunity and leukocyte migration were the most significantly upregulated biological processes among differentially expressed genes (DEGs). Notably, several DEGs associated with "leukocyte migration," such as Vcam1, Cxcl13, and Ccl8, exhibited an increasing trend in transcriptomic and protein expression at three different time points in the seminal vesicles of mice. Additionally, we identified multiple aging-associated DEGs, including P21 and Tnfrsf1b. Two genes (Cd209f and Ccl8) were consistently upregulated across all six regions of the male reproductive glands (testis, epididymis, and seminal vesicle) in the comparison of bulk RNA datasets from 3-month-old and 21-month-old mice. These analyses highlight an enhanced state of immune and inflammatory response in aged seminal vesicles. This study represents the first exploration of the overall transcriptome landscape of seminal vesicles in a murine model of natural aging, offering new insights into the mechanisms underlying aging-related seminal vesicle dysfunction.
    Keywords:  RNA sequencing; Seminal vesicles; aging; gene expression
    DOI:  https://doi.org/10.1080/19396368.2024.2388121
  55. Biosci Rep. 2024 Aug 28. pii: BSR-2018-2312_RET. [Epub ahead of print]44(8):
    Retraction: Bone morphogenetic protein-7 retards cell subculture-induced senescence of human nucleus pulposus cells through activating the PI3K/Akt pathway.
      
    Keywords:  bone morphogenetic protein-7; cell senescence; intervertebral disc degeneration; nucleus pulposus
    DOI:  https://doi.org/10.1042/BSR-2018-2312_RET
  56. Biotechnol Bioeng. 2024 Aug 23.
    Multidose transient transfection of human embryonic kidney 293 cells modulates recombinant adeno-associated virus2/5 Rep protein expression and influences the enrichment fraction of filled capsids.
    Prasanna Srinivasan, Christopher T Canova, Sha Sha, Tam N T Nguyen, John Joseph, Jose Sangerman, Andrew J Maloney, Georgios Katsikis, Rui Wen Ou, Moo Sun Hong, Jaclyn Ng, Arella Yuan, Daniel Antov, Sally Song, Wenyu Chen, Caleb Neufeld, Jacqueline M Wolfrum, Paul W Barone, Anthony J Sinskey, Stacy L Springs, Richard D Braatz.
      Recombinant adeno-associated virus (rAAV) is a commonly used in vivo gene therapy vector because of its nonpathogenicity, long-term transgene expression, broad tropism, and ability to transduce both dividing and nondividing cells. However, rAAV vector production via transient transfection of mammalian cells typically yields a low fraction of filled-to-total capsids (~1%-30% of total capsids produced). Analysis of our previously developed mechanistic model for rAAV2/5 production attributed these low fill fractions to a poorly coordinated timeline between capsid synthesis and viral DNA replication and the repression of later phase capsid formation by Rep proteins. Here, we extend the model by quantifying the expression dynamics of total Rep proteins and their influence on the key steps of rAAV2/5 production using a multiple dosing transfection of human embryonic kidney 293 (HEK293) cells. We report that the availability of preformed empty capsids and viral DNA copies per cell are not limiting to the capsid-filling reaction. However, optimal expression of Rep proteins (<240 ± 13 ag per cell) enables enrichment of the filled capsid population (>12% of total capsids/cell) upstream. Our analysis suggests increased enrichment of filled capsids via regulating the expression of Rep proteins is possible but at the expense of per cell capsid titer in a triple plasmid transfection. Our study reveals an intrinsic limitation of scaling rAAV2/5 vector genome (vg) production and underscores the need for approaches that allow for regulating the expression of Rep proteins to maximize vg titer per cell upstream.
    Keywords:  Adeno‐associated virus; gene therapy; mechanistic modeling; transfection; vector manufacturing
    DOI:  https://doi.org/10.1002/bit.28828
  57. Nature. 2024 Aug 21.
    Tissues stay fit by balancing clearance of dying cells with regeneration.
      
    Keywords:  Cell biology; Regeneration; Stem cells
    DOI:  https://doi.org/10.1038/d41586-024-02637-6
  58. Thyroid Res. 2024 Aug 19. 17(1): 19
    Artemisinin ameliorates thyroid function and complications in adult male hypothyroid rats via upregulation of the L1 cell adhesion molecule.
    Lingling Li, Haifan Xu, Zecheng Hu, Li Li.
      BACKGROUND: Hypothyroidism, a common worldwide syndrome caused by insufficient thyroid hormone secretion, affects number of people at different ages. Artemisinin (ART), a well-known effective agent in the treatment of malaria, also has anti-oxidative stress functions in various diseases. The L1 cell adhesion molecule exerts multiple protective roles in diseased systems. The aim of the present study was to evaluate the role of ART in adult male hypothyroid rats and the underlying mechanisms.METHODS: The propylthiouracil (PTU) rat model was treated with or without 5 mg/kg ART and with or without L1 short-interfering RNA (siRNA), followed by the experiments to determine the effect of ART on thyroid function, depression and anxiety, cognition impairments, liver, kidney and heart functions, and oxidative stress.
    RESULTS: In the current study, it was shown that ART can ameliorate thyroid function, mitigate depression and anxiety symptoms, attenuate cognition impairments, improve liver, kidney and heart functions, and inhibit oxidative stress; however, the effects exerted by ART could not be observed when L1 was silenced by L1 siRNA.
    CONCLUSION: These results indicated that ART can upregulate the L1 cell adhesion molecule to ameliorate thyroid function and the complications in adult male hypothyroid rats, laying the foundation for ART to be a novel strategy for the treatment of hypothyroidism.
    Keywords:  Artemisinin (ART); Hypothyroidism; L1; Oxidative stress
    DOI:  https://doi.org/10.1186/s13044-024-00206-7
  59. DNA Repair (Amst). 2024 Aug 20. pii: S1568-7864(24)00128-9. [Epub ahead of print]142 103752
    From rest to repair: Safeguarding genomic integrity in quiescent cells.
    Chin Wei Brian Leung, Jacob Wall, Fumiko Esashi.
      Quiescence is an important non-pathological state in which cells pause cell cycle progression temporarily, sometimes for decades, until they receive appropriate proliferative stimuli. Quiescent cells make up a significant proportion of the body, and maintaining genomic integrity during quiescence is crucial for tissue structure and function. While cells in quiescence are spared from DNA damage associated with DNA replication or mitosis, they are still exposed to various sources of endogenous DNA damage, including those induced by normal transcription and metabolism. As such, it is vital that cells retain their capacity to effectively repair lesions that may occur and return to the cell cycle without losing their cellular properties. Notably, while DNA repair pathways are often found to be downregulated in quiescent cells, emerging evidence suggests the presence of active or differentially regulated repair mechanisms. This review aims to provide a current understanding of DNA repair processes during quiescence in mammalian systems and sheds light on the potential pathological consequences of inefficient or inaccurate repair in quiescent cells.
    Keywords:  DNA repair; Genome stability; Metabolism; Quiescence; Transcription
    DOI:  https://doi.org/10.1016/j.dnarep.2024.103752
  60. Curr Osteoporos Rep. 2024 Aug 20.
    MicroRNAs and their Modulatory Effect on the Hallmarks of Osteosarcopenia.
    William J Silva, André Cruz, Gustavo Duque.
      PURPOSE OF THE REVIEW: Osteosarcopenia is a geriatric syndrome associated with disability and mortality. This review summarizes the key microRNAs that regulate the hallmarks of sarcopenia and osteoporosis. Our objective was to identify components similarly regulated in the pathology and have therapeutic potential by influencing crucial cellular processes in both bone and skeletal muscle.RECENT FINDINGS: The simultaneous decline in bone and muscle in osteosarcopenia involves a complex crosstalk between these tissues. Recent studies have uncovered several key mechanisms underlying this condition, including the disruption of cellular signaling pathways that regulate bone remodeling and muscle function and regeneration. Accordingly, emerging evidence reveals that dysregulation of microRNAs plays a significant role in the development of each of these hallmarks of osteosarcopenia. Although the recent recognition of osteosarcopenia as a single diagnosis of bone and muscle deterioration has provided new insights into the mechanisms of these underlying age-related diseases, several knowledge gaps have emerged, and a deeper understanding of the role of common microRNAs is still required. In this study, we summarize current evidence on the roles of microRNAs in the pathogenesis of osteosarcopenia and identify potential microRNA targets for treating this condition. Among these, microRNAs-29b and -128 are upregulated in the disease and exert adverse effects by inhibiting IGF-1 and SIRT1, making them potential targets for developing inhibitors of their activity. MicroRNA-21 is closely associated with the occurrence of muscle and bone loss. Conversely, microRNA-199b is downregulated in the disease, and its reduced activity may be related to increased myostatin and GSK3β activity, presenting it as a target for developing analogues that restore its function. Finally, microRNA-672 stands out for its ability to protect skeletal muscle and bone when expressed in the disease, highlighting its potential as a possible therapy for osteosarcopenia.
    Keywords:  Bone-muscle crosstalk; MicroRNAs; Non-coding RNA; Osteoporosis; Osteosarcopenia; Sarcopenia
    DOI:  https://doi.org/10.1007/s11914-024-00880-4
  61. Front Mol Neurosci. 2024 ;17 1408949
    Multi-faceted regulation of CREB family transcription factors.
    Md Arifur Rahman Chowdhury, Md Mazedul Haq, Jeong Hwan Lee, Sangyun Jeong.
      cAMP response element-binding protein (CREB) is a ubiquitously expressed nuclear transcription factor, which can be constitutively activated regardless of external stimuli or be inducibly activated by external factors such as stressors, hormones, neurotransmitters, and growth factors. However, CREB controls diverse biological processes including cell growth, differentiation, proliferation, survival, apoptosis in a cell-type-specific manner. The diverse functions of CREB appear to be due to CREB-mediated differential gene expression that depends on cAMP response elements and multi-faceted regulation of CREB activity. Indeed, the transcriptional activity of CREB is controlled at several levels including alternative splicing, post-translational modification, dimerization, specific transcriptional co-activators, non-coding small RNAs, and epigenetic regulation. In this review, we present versatile regulatory modes of CREB family transcription factors and discuss their functional consequences.
    Keywords:  CREB; alternative splicing; cAMP responsive element; epigenetic modification; post-transcriptional modification; post-translational modification; transcriptional co-activator
    DOI:  https://doi.org/10.3389/fnmol.2024.1408949
  62. Nature. 2024 Aug 21.
    AI can't learn new things forever - an algorithm can fix that.
    Benjamin Thompson, Nick Petrić Howe.
      
    Keywords:  Machine learning; Society; Space physics
    DOI:  https://doi.org/10.1038/d41586-024-02756-0
  63. Food Chem Toxicol. 2024 Aug 15. pii: S0278-6915(24)00507-6. [Epub ahead of print] 114941
    OOCYTE MATURATION, BLASTOCYST AND EMBRYONIC DEVELOPMENT ARE MEDIATED AND ENHANCED VIA HORMESIS.
    Edward J Calabrese, Peter Pressman, A Wallace Hayes, Gaurav Dhawan, Rachna Kapoor, Evgenios Agathokleous, Vittorio Calabrese.
      The present paper provides the first integrative assessment of the capacity of dietary, endogenous and other agents to induce hormetic dose responses in oocytes, their supportive cells such as granulosa cells, blastocyst formation and early stage embryo development with the goal of improving fertility and reproductive success. The analysis showed that numerous agents enhance oocyte maturation and blastocyst/embryonic development in an hormetic fashion. These findings indicate that numerous agents improve oocyte related biological functioning under normal conditions as well as enhancing its capacity to prevent damage from numerous chemical toxins and related stressor agents, including heat and age-related processes in pre-post conditioning and concurrent exposures. The present assessment suggests that hormetic based lifestyles and dietary interventions may offer the potential to enhance healthy reproductive performance with applications to animal husbandry and human biology. The present findings also significantly extend the generality of the hormesis dose response concept to multiple fundamental biological processes (i.e., oocyte maturation, fertilization and blastocyst/embryo development).
    Keywords:  blastocyst; dose response; embryo; granulosa cells; hormesis; oocyte
    DOI:  https://doi.org/10.1016/j.fct.2024.114941
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