bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2024‒09‒01
53 papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Application and prospect of the therapeutic strategy of inhibiting cellular senescence combined with pro-regenerative biomaterials in regenerative medicine.
  2. Polygenic prediction of human longevity on the supposition of pervasive pleiotropy.
  3. A nutrigeroscience approach: Dietary macronutrients and cellular senescence.
  4. Beyond the genome: protecting the proteome may be the key to preventing skin aging.
  5. Targeting organ-specific mitochondrial dysfunction to improve biological aging.
  6. Anoectochilus roxburghii Extract Extends the Lifespan of Caenorhabditis elegans through Activating the daf-16/FoxO Pathway.
  7. Histone chaperone HIRA, promyelocytic leukemia protein, and p62/SQSTM1 coordinate to regulate inflammation during cell senescence.
  8. Quiescence-Origin Senescence: A New Paradigm in Cellular Aging.
  9. P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.
  10. Uncovering key mechanisms and intervention therapies in aging skin.
  11. Molecular Signaling and Clinical Implications in the Human Aging-cancer Cycle.
  12. Harnessing Senescence for Antitumor Immunity to Advance Cancer Treatment.
  13. Trehalose attenuates testicular aging by activating autophagy and improving mitochondrial quality.
  14. Food-derived skin-care ingredient as a promising strategy for skin aging: Current knowledge and future perspectives.
  15. TRPM7 controls skin keratinocyte senescence by targeting intracellular calcium signaling.
  16. Quantum healthy longevity from cells to cities.
  17. Oxidative stress and regulation of adipogenic differentiation capacity by sirtuins in adipose stem cells derived from female patients of advancing age.
  18. Cellular senescence: A novel therapeutic target for central nervous system diseases.
  19. Foundations and implications of Human Aging Omics: A framework for identifying cumulative health risks from embryo to senescence.
  20. Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsO2-exposed auditory cells.
  21. Co-Delivery of Valsartan and Metformin from a Thermosensitive Hydrogel-Nanoparticle System Promotes Collagen Production in Proliferating and Senescent Primary Human Dermal Fibroblasts.
  22. Heterochromatin formation and remodeling by IRTKS condensates counteract cellular senescence.
  23. Molecular Mechanisms of Autophagy Decline during Aging.
  24. Synergistic anti-aging effect of Dendrobium officinale polysaccharide and spermidine: A metabolomics analysis focusing on the regulation of lipid, nucleotide and energy metabolism.
  25. Long-term d-allose administration ameliorates age-related cognitive impairment and loss of bone strength in male mice.
  26. Autophagy Regulates Age-Related Jawbone Loss via LepR+ Stromal Cells.
  27. Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans.
  28. The Antioxidant and Anti-Inflammatory Properties of Bee Pollen from Acorn (Quercus acutissima Carr.) and Darae (Actinidia arguta).
  29. Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases.
  30. Sex-specific modulating role of social support in the associations between oxidative stress, inflammation, and telomere length in older adults.
  31. The promise of machine learning approaches to capture cellular senescence heterogeneity.
  32. The Impairment of Endothelial Autophagy Accelerates Renal Senescence by Ferroptosis and NLRP3 Inflammasome Signaling Pathways with the Disruption of Endothelial Barrier.
  33. Effects of Ginger (Zingiber officinale) on the Hallmarks of Aging.
  34. Role of fibroblast autophagy and proliferation in skin anti-aging.
  35. TRIM16 facilitates SIRT-1-dependent regulation of antioxidant response to alleviate age-related sarcopenia.
  36. Recent Advances in Nanomaterials for Modulation of Stem Cell Differentiation and Its Therapeutic Applications.
  37. Effects of PCNA Stability on the Formation of Mutations.
  38. Exploring the anti-ovarian aging mechanism of He's Yangchao formula: Insights from multi-omics analysis in naturally aged mice.
  39. Regulatory Effects of Senescent Mesenchymal Stem Cells: Endotheliocyte Reaction.
  40. Serotonin neuromodulation directs optic nerve regeneration.
  41. ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone-Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts.
  42. Synthesis, Characterization, and Evaluation of a Hindered Phenol-Linked Benzophenone Hybrid Compound as a Potential Polymer Anti-Aging Agent.
  43. mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes.
  44. Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1.
  45. Osteogenic Protection against Fine Dust with Erucic Acid-Induced Exosomes.
  46. AQP1 differentially orchestrates endothelial cell senescence.
  47. Innovative Tools for DNA Topology Probing in Human Cells Reveal a Build-Up of Positive Supercoils Following Replication Stress at Telomeres and at the FRA3B Fragile Site.
  48. Punica granatum L. leaf extract enhances stress tolerance and promotes healthy longevity through HLH-30/TFEB, DAF16/FOXO, and SKN1/NRF2 crosstalk in Caenorhabditis elegans.
  49. Western diet-induced cognitive and metabolic dysfunctions in aged mice are prevented by rosmarinic acid in a sex-dependent fashion.
  50. Secreted GDF15 maintains transcriptional responses during DNA damage-mediated senescence in human β-cells.
  51. The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice.
  52. Antioxidant Potential of Exosomes in Animal Nutrition.
  53. Author Correction: Rare genetic coding variants associated with human longevity and protection against age-related diseases.
  1. Smart Med. 2023 Nov;2(4): e20230030
    Application and prospect of the therapeutic strategy of inhibiting cellular senescence combined with pro-regenerative biomaterials in regenerative medicine.
    Qianyi Li, Zhenzhen Wang, Nuo Shi, Yang Qi, Wenfei Yao, Jie Yu, Yiming Lu.
      Complete regeneration of damaged tissues/organs has always been the ultimate challenge in regenerative medicine. Aging has long been considered the basis of age-related diseases, as senescent cells gradually accumulate in tissues with increasing age, tissues exhibit aging and normal physiological functions are inhibited. In recent years, in damaged tissues, scholars have found that the number of cells with features of cellular senescence continues to increase over time. The accumulation of senescent cells severely hinders the healing of damaged tissues. Furthermore, by clearing senescent cells or inhibiting the aging microenvironment, damaged tissues regained their original regenerative and repair capabilities. On the other hand, various biomaterials have been proved to have good biocompatibility and can effectively support cell regeneration after injury. Combining the two solutions, inhibiting the cellular senescence in damaged tissues and establishing a pro-regenerative environment through biomaterial technology gradually reveals a new, unexpected treatment strategy applied to the field of regenerative medicine. In this review, we first elucidate the main characteristics of senescent cells from morphological, functional and molecular levels, and discuss in detail the process of accumulation of senescent cells in tissues. Then, we will explore in depth how the accumulation of senescent cells after damage affects tissue repair and regeneration at different stages. Finally, we will turn to how to promote tissue regeneration and repair in the field of regenerative medicine by inhibiting cellular senescence combined with biomaterial technology. Our goal is to understand the relationship between cellular senescence and tissue regeneration through this new perspective, and provide valuable references for the development of new therapeutic strategies in the future.
    Keywords:  aging and regeneration; cell senescence; senolytics and senomorphics; tissue engineering
    DOI:  https://doi.org/10.1002/SMMD.20230030
  2. Sci Rep. 2024 08 28. 14(1): 19981
    Polygenic prediction of human longevity on the supposition of pervasive pleiotropy.
    M Reza Jabalameli, Jhih-Rong Lin, Quanwei Zhang, Zhen Wang, Joydeep Mitra, Nha Nguyen, Tina Gao, Mark Khusidman, Sanish Sathyan, Gil Atzmon, Sofiya Milman, Jan Vijg, Nir Barzilai, Zhengdong D Zhang.
      The highly polygenic nature of human longevity renders pleiotropy an indispensable feature of its genetic architecture. Leveraging the genetic correlation between aging-related traits (ARTs), we aimed to model the additive variance in lifespan as a function of the cumulative liability from pleiotropic segregating variants. We tracked allele frequency changes as a function of viability across different age bins and prioritized 34 variants with an immediate implication on lipid metabolism, body mass index (BMI), and cognitive performance, among other traits, revealed by PheWAS analysis in the UK Biobank. Given the highly complex and non-linear interactions between the genetic determinants of longevity, we reasoned that a composite polygenic score would approximate a substantial portion of the variance in lifespan and developed the integrated longevity genetic scores (iLGSs) for distinguishing exceptional survival. We showed that coefficients derived from our ensemble model could potentially reveal an interesting pattern of genomic pleiotropy specific to lifespan. We assessed the predictive performance of our model for distinguishing the enrichment of exceptional longevity among long-lived individuals in two replication cohorts (the Scripps Wellderly cohort and the Medical Genome Reference Bank (MRGB)) and showed that the median lifespan in the highest decile of our composite prognostic index is up to 4.8 years longer. Finally, using the proteomic correlates of iLGS, we identified protein markers associated with exceptional longevity irrespective of chronological age and prioritized drugs with repurposing potentials for gerotherapeutics. Together, our approach demonstrates a promising framework for polygenic modeling of additive liability conferred by ARTs in defining exceptional longevity and assisting the identification of individuals at a higher risk of mortality for targeted lifestyle modifications earlier in life. Furthermore, the proteomic signature associated with iLGS highlights the functional pathway upstream of the PI3K-Akt that can be effectively targeted to slow down aging and extend lifespan.
    Keywords:  Aging; Centenarians; Common variants; Lifespan; Longevity; Pleiotropy; Polygenic score; Proteomics
    DOI:  https://doi.org/10.1038/s41598-024-69069-0
  3. Cell Metab. 2024 Aug 15. pii: S1550-4131(24)00327-9. [Epub ahead of print]
    A nutrigeroscience approach: Dietary macronutrients and cellular senescence.
    Mariah F Calubag, Paul D Robbins, Dudley W Lamming.
      Cellular senescence, a process in which a cell exits the cell cycle in response to stressors, is one of the hallmarks of aging. Senescence and the senescence-associated secretory phenotype (SASP)-a heterogeneous set of secreted factors that disrupt tissue homeostasis and promote the accumulation of senescent cells-reprogram metabolism and can lead to metabolic dysfunction. Dietary interventions have long been studied as methods to combat age-associated metabolic dysfunction, promote health, and increase lifespan. A growing body of literature suggests that senescence is responsive to diet, both to calories and specific dietary macronutrients, and that the metabolic benefits of dietary interventions may arise in part through reducing senescence. Here, we review what is currently known about dietary macronutrients' effect on senescence and the SASP, the nutrient-responsive molecular mechanisms that may mediate these effects, and the potential for these findings to inform the development of a nutrigeroscience approach to healthy aging.
    Keywords:  branched-chain amino acids; cellular senescence; healthspan; macronutrients; nutrigeroscience; protein; senescence-associated secretory phenotype
    DOI:  https://doi.org/10.1016/j.cmet.2024.07.025
  4. Eur J Dermatol. 2024 Aug 01. 34(4): 355-360
    Beyond the genome: protecting the proteome may be the key to preventing skin aging.
    Brigitte Dréno, Isabelle Benoit, Eric Perrier, Miroslav Radman.
      Skin aging is associated with a progressive decline in physiological functions, skin cancers and, ultimately, death. It may be categorized as intrinsic or extrinsic, whereby intrinsic aging is attributed to chronological and genetic factors. At the molecular level, skin aging involves changes in protein conformation and function. The skin proteome changes constantly, mainly through carbonylation; an irreversible phenomenon leading to protein accumulation as toxic aggregates that impair cellular physiology and accelerate skin aging. This review details the central role of proteostasis during skin aging and why proteome protection may be a promising approach in mitigating skin aging. A comprehensive literature review of 87 articles focusing on the proteome, proteostasis, proteotoxicity, protein carbonylation, and the impact of the damaged proteome on aging, and in particular skin aging, was conducted. Skin aging is associated with deficiencies in the repair mechanisms of DNA, transcriptional control, mitochondrial function, cell cycle control, apoptosis, cellular metabolism, changes in hormonal levels secondary to toxicity of damaged proteins, and cell-to-cell communication for tissue homeostasis, which are largely controlled by proteins. In this context, a damaged proteome that leads to the loss of proteostasis may be considered as the first step in tissue aging. There is growing evidence that a healthy proteome plays a central role in skin and in maintaining healthy tissues, thus slowing down the process of skin aging. Hence, protecting the proteome against oxidative or other damage may be an appropriate strategy to prevent and delay skin aging.
    Keywords:  protein carbonylation; proteome; proteostasis; skin aging
    DOI:  https://doi.org/10.1684/ejd.2024.4739
  5. Pharmacol Ther. 2024 Aug 22. pii: S0163-7258(24)00130-X. [Epub ahead of print]262 108710
    Targeting organ-specific mitochondrial dysfunction to improve biological aging.
    Corina T Madreiter-Sokolowski, Ursula Hiden, Jelena Krstic, Katrin Panzitt, Martin Wagner, Christian Enzinger, Michael Khalil, Mahmoud Abdellatif, Ernst Malle, Tobias Madl, Elena Osto, Markus Schosserer, Christoph J Binder, Andrea Olschewski.
      In an aging society, unveiling new anti-aging strategies to prevent and combat aging-related diseases is of utmost importance. Mitochondria are the primary ATP production sites and key regulators of programmed cell death. Consequently, these highly dynamic organelles play a central role in maintaining tissue function, and mitochondrial dysfunction is a pivotal factor in the progressive age-related decline in cellular homeostasis and organ function. The current review examines recent advances in understanding the interplay between mitochondrial dysfunction and organ-specific aging. Thereby, we dissect molecular mechanisms underlying mitochondrial impairment associated with the deterioration of organ function, exploring the role of mitochondrial DNA, reactive oxygen species homeostasis, metabolic activity, damage-associated molecular patterns, biogenesis, turnover, and dynamics. We also highlight emerging therapeutic strategies in preclinical and clinical tests that are supposed to rejuvenate mitochondrial function, such as antioxidants, mitochondrial biogenesis stimulators, and modulators of mitochondrial turnover and dynamics. Furthermore, we discuss potential benefits and challenges associated with the use of these interventions, emphasizing the need for organ-specific approaches given the unique mitochondrial characteristics of different tissues. In conclusion, this review highlights the therapeutic potential of addressing mitochondrial dysfunction to mitigate organ-specific aging, focusing on the skin, liver, lung, brain, skeletal muscle, and lung, as well as on the reproductive, immune, and cardiovascular systems. Based on a comprehensive understanding of the multifaceted roles of mitochondria, innovative therapeutic strategies may be developed and optimized to combat biological aging and promote healthy aging across diverse organ systems.
    Keywords:  Anti-aging strategies; Mitochondrial dysfunction; Organ-specific aging; ROS homeostasis; Therapeutic interventions
    DOI:  https://doi.org/10.1016/j.pharmthera.2024.108710
  6. Antioxidants (Basel). 2024 Aug 02. pii: 945. [Epub ahead of print]13(8):
    Anoectochilus roxburghii Extract Extends the Lifespan of Caenorhabditis elegans through Activating the daf-16/FoxO Pathway.
    Peng Xu, Jianfeng Wang, Junyi Wang, Xiaoxiao Hu, Wei Wang, Shengmin Lu, Yingkun Sheng.
      As a significant global issue, aging is prompting people's interest in the potential anti-aging properties of Anoectochilus roxburghii (A. roxburghii), a plant traditionally utilized in various Asian countries for its purported benefits in treating diabetes and combating aging. However, the specific anti-aging components and mechanisms of A. roxburghii remain unclear. This study aims to investigate the anti-aging effects and mechanisms of A. roxburghii extract E (ARE). Caenorhabditis elegans (C. elegans) were exposed to media containing different concentrations of ARE whose superior in vitro radical scavenging capacity was thus identified. Lifespan assays, stress resistance tests, and RT-qPCR analyses were conducted to evaluate anti-aging efficacy, reactive oxygen species (ROS) levels, antioxidant enzyme activity, and daf-16, sod-3, and gst-4 levels. Additionally, transcriptomic and metabolomic analyses were performed to elucidate the potential anti-aging mechanisms of ARE. Fluorescence protein assays and gene knockout experiments were employed to validate the impacts of ARE on anti-aging mechanisms. Our results revealed that ARE not only prolonged the lifespan of C. elegans but also mitigated ROS and lipofuscin accumulation, and boosted resistance to UV and heat stress. Furthermore, ARE modulated the expression of pivotal anti-aging genes including daf-16, sod-3, and gst-4, facilitating the nuclear translocation of DAF-16. Significantly, ARE failed to extend the lifespan of daf-16-deficient C. elegans (CF1038), indicating its dependency on the daf-16/FoxO signaling pathway. These results underscored the effectiveness of ARE as a natural agent for enhancing longevity and stress resilience to C. elegans, potentially to human.
    Keywords:  Anoectochilus roxburghii; Caenorhabditis elegans; anti-aging; daf-16/FoxO pathway; lifespan; stress resilience
    DOI:  https://doi.org/10.3390/antiox13080945
  7. Mol Cell. 2024 Aug 16. pii: S1097-2765(24)00660-9. [Epub ahead of print]
    Histone chaperone HIRA, promyelocytic leukemia protein, and p62/SQSTM1 coordinate to regulate inflammation during cell senescence.
    Nirmalya Dasgupta, Xue Lei, Christina Huan Shi, Rouven Arnold, Marcos G Teneche, Karl N Miller, Adarsh Rajesh, Andrew Davis, Valesca Anschau, Alexandre R Campos, Rebecca Gilson, Aaron Havas, Shanshan Yin, Zong Ming Chua, Tianhui Liu, Jessica Proulx, Michael Alcaraz, Mohammed Iqbal Rather, Josue Baeza, David C Schultz, Kevin Y Yip, Shelley L Berger, Peter D Adams.
      Cellular senescence, a stress-induced stable proliferation arrest associated with an inflammatory senescence-associated secretory phenotype (SASP), is a cause of aging. In senescent cells, cytoplasmic chromatin fragments (CCFs) activate SASP via the anti-viral cGAS/STING pathway. Promyelocytic leukemia (PML) protein organizes PML nuclear bodies (NBs), which are also involved in senescence and anti-viral immunity. The HIRA histone H3.3 chaperone localizes to PML NBs in senescent cells. Here, we show that HIRA and PML are essential for SASP expression, tightly linked to HIRA's localization to PML NBs. Inactivation of HIRA does not directly block expression of nuclear factor κB (NF-κB) target genes. Instead, an H3.3-independent HIRA function activates SASP through a CCF-cGAS-STING-TBK1-NF-κB pathway. HIRA physically interacts with p62/SQSTM1, an autophagy regulator and negative SASP regulator. HIRA and p62 co-localize in PML NBs, linked to their antagonistic regulation of SASP, with PML NBs controlling their spatial configuration. These results outline a role for HIRA and PML in the regulation of SASP.
    Keywords:  CCF; HIRA; NF-κB pathway; PML; PML NBs; SASP; cGAS-STING signaling; p62/SQSTM; senescence
    DOI:  https://doi.org/10.1016/j.molcel.2024.08.006
  8. Biomedicines. 2024 Aug 13. pii: 1837. [Epub ahead of print]12(8):
    Quiescence-Origin Senescence: A New Paradigm in Cellular Aging.
    Guang Yao.
      Cellular senescence, traditionally viewed as a consequence of proliferating and growing cells overwhelmed by extensive stresses and damage, has long been recognized as a critical cellular aging mechanism. Recent research, however, has revealed a novel pathway termed "quiescence-origin senescence", where cells directly transition into senescence from the quiescent state, bypassing cell proliferation and growth. This opinion paper presents a framework conceptualizing a continuum between quiescence and senescence with quiescence deepening as a precursor to senescence entry. We explore the triggers and controllers of this process and discuss its biological implications. Given that the majority of cells in the human body are dormant rather than proliferative, understanding quiescence-origin senescence has significant implications for tissue homeostasis, aging, cancer, and various disease processes. The new paradigm in exploring this previously overlooked senescent cell population may reshape our intervention strategies for age-related diseases and tissue regeneration.
    Keywords:  Rb–E2F switch threshold; dormancy state continuum; geroconversion; quiescence; quiescence deepening; senescence
    DOI:  https://doi.org/10.3390/biomedicines12081837
  9. Nat Commun. 2024 Aug 28. 15(1): 7458
    P53-dependent hypusination of eIF5A affects mitochondrial translation and senescence immune surveillance.
    Xiangli Jiang, Ali Hyder Baig, Giuliana Palazzo, Rossella Del Pizzo, Toman Bortecen, Sven Groessl, Esther A Zaal, Cinthia Claudia Amaya Ramirez, Alexander Kowar, Daniela Aviles-Huerta, Celia R Berkers, Wilhelm Palm, Darjus Tschaharganeh, Jeroen Krijgsveld, Fabricio Loayza-Puch.
      Cellular senescence is characterized by a permanent growth arrest and is associated with tissue aging and cancer. Senescent cells secrete a number of different cytokines referred to as the senescence-associated secretory phenotype (SASP), which impacts the surrounding tissue and immune response. Here, we find that senescent cells exhibit higher rates of protein synthesis compared to proliferating cells and identify eIF5A as a crucial regulator of this process. Polyamine metabolism and hypusination of eIF5A play a pivotal role in sustaining elevated levels of protein synthesis in senescent cells. Mechanistically, we identify a p53-dependent program in senescent cells that maintains hypusination levels of eIF5A. Finally, we demonstrate that functional eIF5A is required for synthesizing mitochondrial ribosomal proteins and monitoring the immune clearance of premalignant senescent cells in vivo. Our findings establish an important role of protein synthesis during cellular senescence and suggest a link between eIF5A, polyamine metabolism, and senescence immune surveillance.
    DOI:  https://doi.org/10.1038/s41467-024-51901-w
  10. Cytokine Growth Factor Rev. 2024 Aug 03. pii: S1359-6101(24)00052-2. [Epub ahead of print]
    Uncovering key mechanisms and intervention therapies in aging skin.
    Yuqin Zhang, Lin Liu, Lixia Yue, Yongzhuo Huang, Bing Wang, Peifeng Liu.
      Advancements in understanding skin aging mechanisms, which encompass both external and internal aging processes, have spurred the development of innovative treatments primarily aimed at improving cosmetic appearance. These findings offer the potential for the development of novel therapeutic strategies aimed at achieving long-term, non-therapy-dependent clinical benefits, including the reversal of aging and the mitigation of associated health conditions. Realizing this goal requires further research to establish the safety and efficacy of targeting aging-related skin changes, such as pigmentation, wrinkling, and collagen loss. Systematic investigation is needed to identify the most effective interventions and determine optimal anti-aging treatment strategies. These reviews highlight the features and possible mechanisms of skin aging, as well as the latest progress and future direction of skin aging research, to provide a theoretical basis for new practical anti-skin aging strategies.
    Keywords:  Aging; Mechanisms; Skin; Therapies
    DOI:  https://doi.org/10.1016/j.cytogfr.2024.07.009
  11. Semin Cancer Biol. 2024 Aug 26. pii: S1044-579X(24)00061-0. [Epub ahead of print]
    Molecular Signaling and Clinical Implications in the Human Aging-cancer Cycle.
    Abdol-Hossein Rezaeian, Wenyi Wei.
      It is well documented that aging is associated with cancer, and likewise, cancer survivors display accelerated aging. As the number of aging individuals and cancer survivors continues to grow, it raises additional concerns across society. Therefore, unraveling the molecular mechanisms of aging in tissues is essential to developing effective therapies to fight the aging and cancer diseases in cancer survivors and cancer patients. Indeed, cellular senescence is a critical response, or a natural barrier to suppress the transition of normal cells into cancer cells, however, hypoxia which is physiologically required to maintain the stem cell niche, is increased by aging and inhibits senescence in tissues. Interestingly, oxygen restriction or hypoxia increases longevity and slows the aging process in humans, but hypoxia can also drive angiogenesis to facilitate cancer progression. In addition, cancer treatment is considered as one of the major reasons that drive cellular senescence, subsequently followed by accelerated aging. Several clinical trials have recently evaluated inhibitors to eliminate senescent cells. However, some mechanisms of aging typically can also block cancer cell growth and progression, which might require careful strategy for better clinical outcomes. Here we describe the molecular regulation of aging and cancer in crosstalk with DNA damage and hypoxia signaling pathways in cancer patients and cancer survivors. We also update several therapeutic strategies that might be critical in reversing the cancer treatment-associated aging process.
    Keywords:  aging; cancer; hypoxia; senescence; therapeutic strategies
    DOI:  https://doi.org/10.1016/j.semcancer.2024.08.003
  12. Radiat Res. 2024 Aug 28.
    Harnessing Senescence for Antitumor Immunity to Advance Cancer Treatment.
    Pataje G S Prasanna.
      Considering the limitations and complexities of the cell-killing-based cancer treatment approaches, one could aim to integrate symbiotic advances in many energy delivery technologies and transformational pieces of evidence in research on senescence and immunomodulators to advance cancer treatment. Although senescent cells contribute to drug tolerance, resistance to therapy, tumorigenesis, maladapting cancer phenotypes, tumor relapse, recurrence, and metastasis, emerging pieces of evidence also demonstrate that acutely induced senescent cells in tumors can elicit a strong and lasting antitumor immune response juxtaposed to the immunologically silent apoptotic cells. This commentary is to help develop an unconventional conceptual framework to advance cancer treatment. Accordingly, it will involve transiently inducing senescent cells in tumors at optimal levels to prime the immune system with radiation, then eliminating senescent cells with senolytics (drugs that specifically eliminate senescent cells) to disrupt their positive feedback accumulation (to prevent tumor maladaptation and adverse effects in healthy cells) and unleash long-lasting antitumor immunity with immunomodulators. The approach is reasonably speculative and will require scientifically rigorous "fit-for-purpose," well-controlled preclinical research and development involving dose and schedule optimization of radiation and drugs, using representative in vitro and in vivo cancer models to obtain high-quality data to proceed to clinical studies.
    DOI:  https://doi.org/10.1667/RADE-24-00098.1
  13. Andrology. 2024 Aug 28.
    Trehalose attenuates testicular aging by activating autophagy and improving mitochondrial quality.
    Huaming Xi, Wenjing Shan, Minghui Li, Ziqian Wang, Yuan Li.
      BACKGROUND: Reproductive aging can adversely affect male fertility and the health of offspring. The aging process is accompanied by impaired autophagy. Recent studies have shown that Trehalose plays an important role in the prevention of various diseases by regulating autophagy. However, the roles of Trehalose in testicular aging and reproductive decline remain to be clarified.OBJECTIVE: The present study aimed to evaluate the protective effects of Trehalose on testes in an aging mouse model.
    MATERIALS AND METHODS: In this study, an in vivo aging model in mice by administering D-galactose was established to explore the protective effect of Trehalose on testicular aging. We examined histological changes and related indicators of apoptosis, autophagy, mitochondrial biogenesis, and sperm quality.
    RESULTS: D-galactose treatment induced oxidative stress, apoptosis, and impairment of autophagy of testicular cells in mouse testes. Trehalose administration significantly reduced germ cell apoptosis and DNA damage caused by D-galactose-induced oxidative stress. Notably, Trehalose activated autophagy activity and improved mitochondrial function in testicular cells. Furthermore, Trehalose treatment increased the expression level of the tight junction protein ZO-1, and accelerated clearance of damaged mitochondria in Sertoli cells, indicating that Trehalose ameliorated Sertoli cell function in D-galactose-induced aging testes.
    DISCUSSION AND CONCLUSION: These findings suggest that Trehalose administration activated the autophagy activity in testicular cells and improved mitochondrial function, thereby effectively preventing testicular aging. Trehalose and its activated autophagy are crucial for preventing testicular aging, thus restoring autophagy activity by administering Trehalose could be a promising means to delay aging.
    Keywords:  autophagy; mitochondria; oxidative stress; testicular aging; trehalose
    DOI:  https://doi.org/10.1111/andr.13746
  14. Colloids Surf B Biointerfaces. 2024 Aug 22. pii: S0927-7765(24)00429-6. [Epub ahead of print]244 114170
    Food-derived skin-care ingredient as a promising strategy for skin aging: Current knowledge and future perspectives.
    Zichun Jin, Peng Zhang, Huan Huang, Jialin Liu, Chaoping Jiang, Hanyuan Zhang, Lu Ren, Bingkun Sun, Xianghan Chang, Tingyue Gao, Wenxiu Sun.
      Skin aging involves complex biochemical reactions and has attracted a growing concern recently. For it, there is a great desire to replace the hazardous and easy-recurring "therapy means" with "daily care" based on some natural and healthy ingredients. According to a novel theory called "homology of cosmetic and food", the safety, efficacy and accessibility of food-derived skin-care ingredients offer an attractive option for combating skin aging, which will be an inevitable trend of dermatology in the future. Ultraviolet (UV) radiation is a major trigger of skin aging. It acts on the skin and generates reactive oxygen species, which causing oxidative stress. More, matrix metalloproteinase and melanin levels are also upregulated by the UV-activated mitogen-activated protein kinase (MAPK) pathway and tyrosinase, respectively, resulting in collagen degradation and melanin deposition in the extracellular matrix. Through the existing studies, the relevant key biomarkers and biochemical pathways can be effectively controlled by skin-care ingredients from animal-derived and plant-derived foods as well as traditional herbs, thus preserving human skin from UV-induced aging in terms of antioxidant, collagen protection and melanin inhibition. To extend their application potential, some carriers represented by nanoliposomes can facilitate the transdermal absorption of food-derived skin-care ingredients by the variation of molecular weight and lipid solubility. The present review will provide an overview of the trigger mechanisms of skin aging, and focus on the molecular biology aspects of food-derived skin-care ingredients in skin matrix and the critical summarize of their research state.
    Keywords:  Antioxidation; Collagen; Cosmetic; Food-derived functional ingredients; Skin aging
    DOI:  https://doi.org/10.1016/j.colsurfb.2024.114170
  15. FEBS J. 2024 Aug 26.
    TRPM7 controls skin keratinocyte senescence by targeting intracellular calcium signaling.
    Xingjie Ma, Dandan Qi, Xiaoming Sun, Yue Gao, Jiang Ma, Jinghui Yang, Qingtong Shi, Guangfa Wei, Hualing Li, Weili Liu, Juping Chen.
      Cellular senescence is described as an irreversible cell cycle arrest for proliferating cells and is associated with the secretion of senescence associated secretory phenotype factors. It has been known to accumulate with age and is regarded as a key driver of aging-associated skin pathologies. However, the lack of markers of skin senescence and partially understood skin cellular senescence mechanisms has limited the exploration of skin aging and anti-skin aging strategies. Recently, intracellular calcium signaling has emerged as an important regulator of cellular senescence and aging. However, little is known about the modulation of skin cellular senescence by calcium-associated factors. Here, we found that the expression of calcium channel transient receptor potential melastatin 7 (TRPM7) is elevated during skin keratinocyte senescence and aging. Importantly, TRPM7 promotes skin keratinocyte senescence by triggering intracellular calcium transfer from the endoplasmic reticulum to the mitochondria; accumulation of mitochondrial calcium then induces a drop in mitochondrial membrane potential and reactive oxygen species production, leading to subsequent nuclear enlargement and DNA damage. Altogether, these findings indicate that TRPM7 controls skin keratinocyte senescence through regulating intracellular calcium signaling, and thus, shed light on novel strategies for anti-skin aging therapy.
    Keywords:  DNA damage; ROS; TRPM7; calcium signaling; skin cellular senescence
    DOI:  https://doi.org/10.1111/febs.17252
  16. Front Aging. 2024 ;5 1416447
    Quantum healthy longevity from cells to cities.
    Tina Woods, Nic Palmarini, Lynne Corner, Richard Siow.
      
    Keywords:  biomarkers; exposome; healthspan; healthy longevity; resilience
    DOI:  https://doi.org/10.3389/fragi.2024.1416447
  17. Sci Rep. 2024 08 27. 14(1): 19885
    Oxidative stress and regulation of adipogenic differentiation capacity by sirtuins in adipose stem cells derived from female patients of advancing age.
    Anne Bernhardt, Alan Jamil, Md Tanvir Morshed, Pia Ponnath, Veronika Gille, Nadine Stephan, Heinrich Sauer, Maria Wartenberg.
      Patient age is critical for mesenchymal stem cell quality and differentiation capacity. We demonstrate that proliferation and adipogenic capacity of subcutaneous adipose stem cells (ASCs) from female patients declined with advanced age, associated with reduction in cell nucleus size, increase in nuclear lamina protein lamin B1/B2, and lamin A, upregulation of senescence marker p16INK4a and senescence-associated β-galactosidase activity. Adipogenic induction resulted in differentiation of adipocytes and upregulation of adipogenic genes CCAAT enhancer binding protein alpha, fatty acid binding protein 4, lipoprotein lipase, and peroxisome proliferator-activated receptor-γ, which was not affected by the Sirt-1 activator YK-3-237 or the Sirt-1 inhibitor EX-527. Protein expression of the stem cell markers Oct4 and Sox2 was not significantly downregulated with advanced patient age. Mitochondrial reactive oxygen species were increased in ASCs from old-aged patients, whereas protein expression of NADPH oxidases NOX1 and NOX4 was downregulated, and dual oxidase isoforms remained unchanged. Generation of nitric oxide and iNOS expression was downregulated. Protein expression of Sirt-1 and Sirt-3 decreased with patient age, whereas Sirt-2 and Sirt-5 remained unchanged. Induction of adipogenesis stimulated protein expression of Sirt-1 and Sirt-3, which was not affected upon pre-incubation with the Sirt-1-activator YK-3-237 or the Sirt-1-inhibitor EX-527. The Sirt-1 inhibitor Sirtinol downregulated adiponectin protein expression and the number of adipocytes, whereas YK-3-237 exerted stimulatory effects. In summary, our data demonstrate increased oxidative stress in ASCs of aging patients, and decline of adipogenic capacity due to Sirt-1- mediated adiponectin downregulation in elderly patients.
    Keywords:  Adipogenesis; Adipose stem cells; Oxidative stress; Sirtuins
    DOI:  https://doi.org/10.1038/s41598-024-70382-x
  18. Biomed Pharmacother. 2024 Aug 24. pii: S0753-3322(24)01195-8. [Epub ahead of print]179 117311
    Cellular senescence: A novel therapeutic target for central nervous system diseases.
    Shuang-Yin Lei, Yang Qu, Yu-Qian Yang, Jia-Cheng Liu, Yi-Fei Zhang, Sheng-Yu Zhou, Qian-Yan He, Hang Jin, Yi Yang, Zhen-Ni Guo.
      The underlying mechanisms of diseases affecting the central nervous system (CNS) remain unclear, limiting the development of effective therapeutic strategies. Remarkably, cellular senescence, a biological phenomenon observed in cultured fibroblasts in vitro, is a crucial intrinsic mechanism that influences homeostasis of the brain microenvironment and contributes to the onset and progression of CNS diseases. Cellular senescence has been observed in disease models established in vitro and in vivo and in bodily fluids or tissue components from patients with CNS diseases. These findings highlight cellular senescence as a promising target for preventing and treating CNS diseases. Consequently, emerging novel therapies targeting senescent cells have exhibited promising therapeutic effects in preclinical and clinical studies on aging-related diseases. These innovative therapies can potentially delay brain cell loss and functional changes, improve the prognosis of CNS diseases, and provide alternative treatments for patients. In this study, we examined the relevant advancements in this field, particularly focusing on the targeting of senescent cells in the brain for the treatment of chronic neurodegenerative diseases (e.g., Alzheimer's disease, Parkinson's disease, and multiple sclerosis) and acute neurotraumatic insults (e.g., ischemic stroke, spinal cord injury, and traumatic brain injury).
    Keywords:  Cellular senescence; Central nervous system diseases; Neurodegenerative diseases; Senescence; Senolytics
    DOI:  https://doi.org/10.1016/j.biopha.2024.117311
  19. Sci Bull (Beijing). 2024 Aug 02. pii: S2095-9273(24)00537-1. [Epub ahead of print]
    Foundations and implications of Human Aging Omics: A framework for identifying cumulative health risks from embryo to senescence.
    Xiaoying Zheng, Binbin Su, Yihao Zhao, Chen Chen, Bruno Vellas, Jean-Pierre Michel, Ruitai Shao.
      
    DOI:  https://doi.org/10.1016/j.scib.2024.04.073
  20. Cell Death Discov. 2024 Aug 28. 10(1): 382
    Premature senescence is regulated by crosstalk among TFEB, the autophagy lysosomal pathway and ROS derived from damaged mitochondria in NaAsO2-exposed auditory cells.
    Yuna Suzuki, Ken Hayashi, Fumiyuki Goto, Yasuyuki Nomura, Chisato Fujimoto, Makoto Makishima.
      Age-related hearing loss (ARHL) is one of the most prevalent types of sensory decline in a superaging society. Although various studies have focused on the effect of oxidative stress on the inner ear as an inducer of ARHL, there are no effective preventive approaches for ARHL. Recent studies have suggested that oxidative stress-induced DNA damage responses (oxidative DDRs) drive cochlear cell senescence and contribute to accelerated ARHL, and autophagy could function as a defense mechanism against cellular senescence in auditory cells. However, the underlying mechanism remains unclear. Sodium arsenite (NaAsO2) is a unique oxidative stress inducer associated with reactive oxygen species (ROS) that causes high-tone hearing loss similar to ARHL. Transcription factor EB (TFEB) functions as a master regulator of the autophagy‒lysosome pathway (ALP), which is a potential target during aging and the pathogenesis of various age-related diseases. Here, we focused on the function of TFEB and the impact of intracellular ROS as a potential target for ARHL treatment in a NaAsO2-induced auditory premature senescence model. Our results suggested that short exposure to NaAsO2 leads to DNA damage, lysosomal damage and mitochondrial damage in auditory cells, triggering temporary signals for TFEB transport into the nucleus and, as a result, causing insufficient autophagic flux and declines in lysosomal function and biogenesis and mitochondrial quality. Then, intracellular ROS derived from damaged mitochondria play a role as a second messenger to induce premature senescence in auditory cells. These findings suggest that TFEB activation via transport into the nucleus contributes to anti-senescence activity in auditory cells and represents a new therapeutic target for ARHL. We have revealed the potential function of TFEB as a master regulator of the induction of oxidative stress-induced premature senescence and the senescence-associated secretion phenotype (SASP) in auditory cells, which regulates ALP and controls mitochondrial quality through ROS production.
    DOI:  https://doi.org/10.1038/s41420-024-02139-4
  21. Biomacromolecules. 2024 Aug 26.
    Co-Delivery of Valsartan and Metformin from a Thermosensitive Hydrogel-Nanoparticle System Promotes Collagen Production in Proliferating and Senescent Primary Human Dermal Fibroblasts.
    Paul M Kuhn, Siwei Chen, Aditya Venkatraman, Peter M Abadir, Jeremy D Walston, Efrosini Kokkoli.
      Aging negatively impacts skin health, notably through the senescent cell phenotype, which reduces collagen production and leads to thinner, more fragile skin prone to injuries and chronic wounds. We designed a drug delivery system that addresses these age-related issues using a hybrid hydrogel-nanoparticle system that utilizes a poly(δ-valerolactone-co-lactide)-b-poly(ethylene-glycol)-b-poly(δ-valerolactone-co-lactide) (PVLA-PEG-PVLA) hydrogel. This hydrogel allows for the local, extended release of therapeutics targeting both proliferating and senescent cells. The PVLA-PEG-PVLA hydrogel entrapped valsartan, and metformin-loaded liposomes functionalized with a fibronectin-mimetic peptide, PR_b. Metformin acts as a senomorphic, reversing aspects of cellular senescence, and valsartan, an angiotensin receptor blocker, promotes collagen production. This combination treatment partially reversed the senescent phenotype and improved collagen production in senescent dermal fibroblasts from both young and old adults. Our codelivery hydrogel-nanoparticle system offers a promising treatment for improving age-related dermal pathologies.
    DOI:  https://doi.org/10.1021/acs.biomac.3c01461
  22. EMBO J. 2024 Aug 27.
    Heterochromatin formation and remodeling by IRTKS condensates counteract cellular senescence.
    Jia Xie, Zhao-Ning Lu, Shi-Hao Bai, Xiao-Fang Cui, He-Yuan Lian, Chen-Yi Xie, Na Wang, Lan Wang, Ze-Guang Han.
      Heterochromatin, a key component of the eukaryotic nucleus, is fundamental to the regulation of genome stability, gene expression and cellular functions. However, the factors and mechanisms involved in heterochromatin formation and maintenance still remain largely unknown. Here, we show that insulin receptor tyrosine kinase substrate (IRTKS), an I-BAR domain protein, is indispensable for constitutive heterochromatin formation via liquid‒liquid phase separation (LLPS). In particular, IRTKS droplets can infiltrate heterochromatin condensates composed of HP1α and diverse DNA-bound nucleosomes. IRTKS can stabilize HP1α by recruiting the E2 ligase Ubc9 to SUMOylate HP1α, which enables it to form larger phase-separated droplets than unmodified HP1α. Furthermore, IRTKS deficiency leads to loss of heterochromatin, resulting in genome-wide changes in chromatin accessibility and aberrant transcription of repetitive DNA elements. This leads to activation of cGAS-STING pathway and type-I interferon (IFN-I) signaling, as well as to the induction of cellular senescence and senescence-associated secretory phenotype (SASP) responses. Collectively, our findings establish a mechanism by which IRTKS condensates consolidate constitutive heterochromatin, revealing an unexpected role of IRTKS as an epigenetic mediator of cellular senescence.
    Keywords:  Cellular Senescence; Heterochromatin Formation; IRTKS; Liquid-Liquid Phase Separation; SUMOylation
    DOI:  https://doi.org/10.1038/s44318-024-00212-3
  23. Cells. 2024 Aug 16. pii: 1364. [Epub ahead of print]13(16):
    Molecular Mechanisms of Autophagy Decline during Aging.
    Shaun H Y Lim, Malene Hansen, Caroline Kumsta.
      Macroautophagy (hereafter autophagy) is a cellular recycling process that degrades cytoplasmic components, such as protein aggregates and mitochondria, and is associated with longevity and health in multiple organisms. While mounting evidence supports that autophagy declines with age, the underlying molecular mechanisms remain unclear. Since autophagy is a complex, multistep process, orchestrated by more than 40 autophagy-related proteins with tissue-specific expression patterns and context-dependent regulation, it is challenging to determine how autophagy fails with age. In this review, we describe the individual steps of the autophagy process and summarize the age-dependent molecular changes reported to occur in specific steps of the pathway that could impact autophagy. Moreover, we describe how genetic manipulations of autophagy-related genes can affect lifespan and healthspan through studies in model organisms and age-related disease models. Understanding the age-related changes in each step of the autophagy process may prove useful in developing approaches to prevent autophagy decline and help combat a number of age-related diseases with dysregulated autophagy.
    Keywords:  aging; autophagy; lysosomes; proteolysis; proteostasis
    DOI:  https://doi.org/10.3390/cells13161364
  24. Int J Biol Macromol. 2024 Aug 26. pii: S0141-8130(24)05904-X. [Epub ahead of print]278(Pt 4): 135098
    Synergistic anti-aging effect of Dendrobium officinale polysaccharide and spermidine: A metabolomics analysis focusing on the regulation of lipid, nucleotide and energy metabolism.
    Hui Duan, Qun Yu, Yang Ni, Jinwei Li, Leilei Yu, Xiaowei Yan, Liuping Fan.
      The importance of synergy has been underscored in recent medical research for augmenting the efficacy of therapeutic interventions, targeting multiple biological pathways simultaneously. Our prior research elucidated that Dendrobium officinale polysaccharide (DOP) has the potential to prolong the lifespan of Caenorhabditis elegans (C. elegans) via regulating gut microbiota. Concurrently, spermidine (Spd), as a mimicking caloric restriction, facilitates autophagy and exerts a pronounced anti-aging effect. To enhance the anti-aging capabilities of DOP, we conducted a comprehensive study examining the combined effects of DOP and Spd in C. elegans, incorporating metabolomics analysis to investigate the underlying mechanisms. A combination of 250 mg/L DOP and 29.0 mg/L Spd yielded the most favorable outcomes in lifespan extension, evidencing a synergistic effect with a combination index (CI) of 0.65. In oxidative and heat stress tolerance assays, the observed CIs were 0.50 and 0.33, respectively. Metabolomic analysis highlighted significant alterations in metabolites related to lipid, nucleotide and energy metabolism, notably regulating glycerol 3-phosphate, linoleoyl glycerol, docosapentaenoic acid and β-nicotinamide mononucleotide, nicotinamide adenine dinucleotide. The effects of DS on lipid metabolism were further validated using Oil Red O staining and triglyceride level in C. elegans. The results indicated that DS may primarily be via modulating lipid metabolism. To further confirm these findings, a high-fat diet-induced mouse model was employed. Consequently, it can be inferred that the synergistic anti-aging impact of DOP and Spd is likely mediated primarily through alterations in lipid metabolic processes.
    Keywords:  Dendrobium officinale polysaccharide; Spermidine; Synergistic anti-aging
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.135098
  25. Exp Gerontol. 2024 Aug 21. pii: S0531-5565(24)00201-8. [Epub ahead of print] 112555
    Long-term d-allose administration ameliorates age-related cognitive impairment and loss of bone strength in male mice.
    Tomoya Shintani, Shuichi Yanai, Akane Kanasaki, Tetsuo Iida, Shogo Endo.
      Age-related physical and cognitive decline may be ameliorated by consuming functional foods. d-Allose is reported to have multiple health benefits, it may temper aging phenotypes, particularly brain function. We investigated whether d-allose supplementation improves cognitive function. A standard battery of behavioral tests was administered to 18-month-old male mice after consuming diet containing 3 % d-allose for 6 months. Following a wire-hanging test, an open-field test, Morris water maze, fear-conditioning, and an analgesia test were sequentially performed. Bone density and strength were assessed afterwards. Possible mechanism(s) under-lying memory changes in hippocampus were also examined with a DNA microarray. d-Allose failed to influence muscle strength, locomotor activity and anxiety, fear memory, or pain sensitivity. However, d-allose improved hippocampus-dependent spatial learning and memory, and it may contribute to increase bone strength. d-Allose also changed the expression of some genes in hippocampus involved in cognitive functions. Long-term d-allose supplementation appears to modestly change aging phenotypes and improve spatial memory.
    Keywords:  Behavioral experiments; Bone; D-Allose; Learning; Memory; Rare sugars
    DOI:  https://doi.org/10.1016/j.exger.2024.112555
  26. J Dent Res. 2024 Aug 26. 220345241264810
    Autophagy Regulates Age-Related Jawbone Loss via LepR+ Stromal Cells.
    B Sun, Y Xu, H Wang, F Wang, Q Li, Y Chen, Z Wang.
      Bone aging and decreased autophagic activity are related but poorly explored in the jawbone. This study aimed to characterize the aging jawbones and jawbone-derived stromal cells (JBSCs) and determine the role of autophagy in jawbone mass decline. We observed that the jawbones of older individuals and mice exhibited similar age-related bone loss. Furthermore, leptin receptor (LepR)-lineage cells served as the primary source for in vitro cultured and expanded JBSCs, referred to as LepR-Cre+/JBSCs. RNA-sequencing data from the jawbones and LepR-Cre+/JBSCs showed the upregulated expression of the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway during aging. Through single-cell transcriptomics, we identified a decrease in the proportion of osteogenic lineage cells and the activation of the PI3K/AKT pathway in LepR-lineage cells in aging bone tissues. Reduced basal autophagic activity, diminished autophagic flux, and decreased osteogenesis occurred in the jawbones and LepR-Cre+/JBSCs from older mice (O-mice; O-JBSCs). Pharmacologic and constitutive autophagy activation alleviated the impaired osteogenesis in O-JBSCs. In addition, the suppression of mTOR-induced autophagy improved the aging phenotype of O-JBSCs. The activation of autophagy in LepR-Cre+/JBSCs using chemical autophagic activators reduced the alveolar bone resorption in O-mice. Therefore, our study demonstrated that ATG molecules and pathways are crucial in jawbone aging, providing novel approaches to understanding age-related jawbone loss.
    Keywords:  RNA-seq; aging; bone resorption; jaw; leptin receptor; osteogenesis
    DOI:  https://doi.org/10.1177/00220345241264810
  27. Biogerontology. 2024 Aug 28.
    Immunoinformatic-based drug design utilizing hesperetin to target CISD2 activation for liver aging in humans.
    Saad Ilyas Baig, Maria Naseer, Abdur-Rehman Munir, Yasir Ali, Muhammad Asif Razzaq.
      The CISD protein family, consisting of CISD1, CISD2, and CISD3, encodes proteins that feature CDGSH iron-sulfur domains crucial for cellular functions and share a common 2Fe-2S domain. CISD2, which is pivotal in cells, regulates intracellular calcium levels, maintains the endoplasmic reticulum and mitochondrial function, and is associated with longevity and overall health, with exercise stimulating CISD2 production. However, CISD2 expression decreases with age, impacting age-related processes. According to in silico docking, HST is a CISD2 activator that affects metabolic dysfunction and age-related illnesses by affecting metabolic pathways. This study investigated the ability of CISD2 and HST to reduce age-related ailments, with a particular emphasis on liver aging. CISD2 deficiency has a major effect on the function of cells, as it undermines the integrity of the ER, mitochondria, and calcium homeostasis. It also increases susceptibility to oxidative stress and metabolic dysregulation, which is linked to Wolfram syndrome and exacerbates age-related illnesses and metabolic disorders. By shielding cells from stress, CISD2 extends the life of cells and maintains liver health as people age. Its protective effecfts on the liver during aging are further enhanced by its control of translation factors such as Nrf2 and IL-6. This work paves the way for future investigations and clinical applications by examining the structural and functional properties of CISD2 and the interaction between CISD2 and HST. This highlights the therapeutic potential of these findings in promoting healthy livers in humans and battling age-related illnesses.
    Keywords:  Age-related ailments; CISD2; Hesperetin; Humans; In- silico docking; Lifespan; Liver-aging; Therapeutic agent
    DOI:  https://doi.org/10.1007/s10522-024-10130-w
  28. Antioxidants (Basel). 2024 Aug 13. pii: 981. [Epub ahead of print]13(8):
    The Antioxidant and Anti-Inflammatory Properties of Bee Pollen from Acorn (Quercus acutissima Carr.) and Darae (Actinidia arguta).
    Jeong-Eun Kwak, Joo-Yeon Lee, Ji-Yoon Baek, Sun Wook Kim, Mok-Ryeon Ahn.
      Aging is a complex biological process characterized by a progressive decline in physical function and an increased risk of age-related chronic diseases. Additionally, oxidative stress is known to cause severe tissue damage and inflammation. Pollens from acorn and darae are extensively produced in Korea. However, the underlying molecular mechanisms of these components under the conditions of inflammation and oxidative stress remain largely unknown. This study aimed to investigate the effect of bee pollen components on lipopolysaccharide (LPS)-induced RAW 264.7 mouse macrophages. This study demonstrates that acorn and darae significantly inhibit the LPS-induced production of inflammatory mediators, such as nitric oxide (NO) and prostaglandin E2 (PGE2), in RAW 264.7 cells. Specifically, bee pollen from acorn reduces NO production by 69.23 ± 0.04% and PGE2 production by 44.16 ± 0.08%, while bee pollen from darae decreases NO production by 78.21 ± 0.06% and PGE2 production by 66.23 ± 0.1%. Furthermore, bee pollen from acorn and darae reduced active oxygen species (ROS) production by 47.01 ± 0.5% and 60 ± 0.9%, respectively. It increased the nuclear potential of nuclear factor erythroid 2-related factor 2 (Nrf2) in LPS-stimulated RAW 264.7 cells. Moreover, treatment with acorn and darae abolished the nuclear potential of nuclear factor κB (NF-κB) and reduced the expression of extracellular signal-associated kinase (ERK) and c-Jun N-terminal kinase (JNK) phosphorylation in LPS-stimulated RAW 264.7 cells. Specifically, acorn decreased NF-κB nuclear potential by 90.01 ± 0.3%, ERK phosphorylation by 76.19 ± 1.1%, and JNK phosphorylation by 57.14 ± 1.2%. Similarly, darae reduced NF-κB nuclear potential by 92.21 ± 0.5%, ERK phosphorylation by 61.11 ± 0.8%, and JNK phosphorylation by 59.72 ± 1.12%. These results suggest that acorn and darae could be potential antioxidants and anti-inflammatory agents.
    Keywords:  NF-κB; ROS; anti-inflammatory; antioxidant; bee pollen
    DOI:  https://doi.org/10.3390/antiox13080981
  29. Antioxidants (Basel). 2024 Aug 14. pii: 985. [Epub ahead of print]13(8):
    Gut Microbiota Dysbiosis, Oxidative Stress, Inflammation, and Epigenetic Alterations in Metabolic Diseases.
    Hamid Mostafavi Abdolmaleky, Jin-Rong Zhou.
      Gut dysbiosis, resulting from an imbalance in the gut microbiome, can induce excessive production of reactive oxygen species (ROS), leading to inflammation, DNA damage, activation of the immune system, and epigenetic alterations of critical genes involved in the metabolic pathways. Gut dysbiosis-induced inflammation can also disrupt the gut barrier integrity and increase intestinal permeability, which allows gut-derived toxic products to enter the liver and systemic circulation, further triggering oxidative stress, inflammation, and epigenetic alterations associated with metabolic diseases. However, specific gut-derived metabolites, such as short-chain fatty acids (SCFAs), lactate, and vitamins, can modulate oxidative stress and the immune system through epigenetic mechanisms, thereby improving metabolic function. Gut microbiota and diet-induced metabolic diseases, such as obesity, insulin resistance, dyslipidemia, and hypertension, can transfer to the next generation, involving epigenetic mechanisms. In this review, we will introduce the key epigenetic alterations that, along with gut dysbiosis and ROS, are engaged in developing metabolic diseases. Finally, we will discuss potential therapeutic interventions such as dietary modifications, prebiotics, probiotics, postbiotics, and fecal microbiota transplantation, which may reduce oxidative stress and inflammation associated with metabolic syndrome by altering gut microbiota and epigenetic alterations. In summary, this review highlights the crucial role of gut microbiota dysbiosis, oxidative stress, and inflammation in the pathogenesis of metabolic diseases, with a particular focus on epigenetic alterations (including histone modifications, DNA methylomics, and RNA interference) and potential interventions that may prevent or improve metabolic diseases.
    Keywords:  epigenetic; gut dysbiosis; inflammation; metabolic diseases; microbiome; microbiota; oxidative stress; transgenerational
    DOI:  https://doi.org/10.3390/antiox13080985
  30. J Behav Med. 2024 Aug 23.
    Sex-specific modulating role of social support in the associations between oxidative stress, inflammation, and telomere length in older adults.
    Zhou Jin, Xuejian Liu, Haonan Guo, Sixuan Chen, Xianghe Zhu, Sipei Pan, Yili Wu.
      Telomere length, a biomarker of human aging, is related to adverse health outcomes. Growing evidence indicates that oxidative stress and inflammation contributes to telomere shortening, whereas social support may protect from telomere shortening. Despite sex differences in telomere length and social support, little is known about whether there are sex differences in the relationship between oxidative stress/inflammation and telomere length, and sex-specific moderating roles of social support in older adults. Using data from the National Health and Nutrition Examination Survey (NHANES) 1999-2002, this study assessed whether the associations between oxidative stress/inflammation and telomere length vary with sex and explored social support as a moderator in these associations among 2289 older adults. Oxidative stress was measured based on serum Gamma-glutamyl transferase (GGT), and inflammation was measured based on C-reactive protein (CRP). After adjusting for the covariates, GGT was significantly associated with telomere length in females only (β =  - 0.037, 95% CI =  - 0.070, - 0.005), while CRP was associated with telomere length in males only (β =  - 0.019, 95% CI =  - 0.035, - 0.002). Moreover, high social support mitigated the negative association between GGT and telomere length, which was more evident in females. Furthermore, social support moderated the association between CRP and telomere length in males aged 70 and above. Our findings indicated that biological mechanisms related to telomere length may vary with sex, while social support plays a sex-specific moderating role.
    Keywords:  Inflammation; Moderation; NHANES; Oxidative stress; Sex difference; Social support; Telomere length
    DOI:  https://doi.org/10.1007/s10865-024-00515-0
  31. Nat Aging. 2024 Aug 26.
    The promise of machine learning approaches to capture cellular senescence heterogeneity.
    Imanol Duran, Cleo L Bishop, Jesús Gil, Ryan Wallis.
      
    DOI:  https://doi.org/10.1038/s43587-024-00703-2
  32. Antioxidants (Basel). 2024 Jul 23. pii: 886. [Epub ahead of print]13(8):
    The Impairment of Endothelial Autophagy Accelerates Renal Senescence by Ferroptosis and NLRP3 Inflammasome Signaling Pathways with the Disruption of Endothelial Barrier.
    Jin Won Kim, Sun Ah Nam, Eun-Sil Koh, Hyung Wook Kim, Sua Kim, Jin Ju Woo, Yong Kyun Kim.
      Autophagy is a cellular process that degrades damaged cytoplasmic components and regulates cell death. The homeostasis of endothelial cells (ECs) is crucial for the preservation of glomerular structure and function in aging. Here, we investigated the precise mechanisms of endothelial autophagy in renal aging. The genetic deletion of Atg7 in the ECs of Atg7flox/flox;Tie2-Cre mice accelerated aging-related glomerulopathy and tubulointerstitial fibrosis. The EC-specific Atg7 deletion in aging mice induced the detachment of EC with the disruption of glomerular basement membrane (GBM) assembly and increased podocyte loss resulting in microalbuminuria. A Transwell co-culture system of ECs and kidney organoids showed that the iron and oxidative stress induce the disruption of the endothelial barrier and increase vascular permeability, which was accelerated by the inhibition of autophagy. This resulted in the leakage of iron through the endothelial barrier into kidney organoids and increased oxidative stress, which led to ferroptotic cell death. The ferritin accumulation was increased in the kidneys of the EC-specific Atg7-deficient aging mice and upregulated the NLRP3 inflammasome signaling pathway. The pharmacologic inhibition of ferroptosis with liproxstatin-1 recovered the disrupted endothelial barrier and reversed the decreased expression of GPX4, as well as NLRP3 and IL-1β, in endothelial autophagy-deficient aged mice, which attenuated aging-related renal injury including the apoptosis of renal cells, abnormal structures of GBM, and tubulointerstitial fibrosis. Our data showed that endothelial autophagy is essential for the maintenance of the endothelial barrier during renal aging and the impairment of endothelial autophagy accelerates renal senescence by ferroptosis and NLRP3 inflammasome signaling pathways. These processes may be attractive therapeutic targets to reduce cellular injury from renal aging.
    Keywords:  aging; autophagy; kidney; liproxstatin-1
    DOI:  https://doi.org/10.3390/antiox13080886
  33. Biomolecules. 2024 Aug 02. pii: 940. [Epub ahead of print]14(8):
    Effects of Ginger (Zingiber officinale) on the Hallmarks of Aging.
    Maima Matin, Tanuj Joshi, Dongdong Wang, Nikolay T Tzvetkov, Farhan Bin Matin, Agnieszka Wierzbicka, Artur Jóźwik, Jarosław Olav Horbańczuk, Atanas G Atanasov.
      Ginger (Zingiber officinale Roscoe) is broadly used as a traditional remedy and food ingredient, and numerous preclinical and clinical studies have demonstrated health benefits in a range of age-related disorders. Moreover, longevity-promoting effects have been demonstrated in several (preclinical) research models. With this work, we aimed to comprehensively review the reported effects of ginger and its bioactive constituents on the twelve established hallmarks of aging, with the ultimate goal of gaining a deeper understanding of the potential for future interventions in the area of longevity-extension and counteracting of aging-related diseases. The reviewed literature supports the favorable effects of ginger and some of its constituents on all twelve hallmarks of aging, with a particularly high number of animal research studies indicating counteraction of nutrient-sensing dysregulations, mitochondrial dysfunction, chronic inflammation, and dysbiosis. On this background, validation in human clinical trials is still insufficient or is entirely missing, with the exception of some studies indicating positive effects on deregulated nutrient-sensing, chronic inflammation, and dysbiosis. Thus, the existing body of literature clearly supports the potential of ginger to be further studied in clinical trials as a supplement for the promotion of both lifespan and health span.
    Keywords:  ginger; hallmarks of aging; health span; inflammation; life-extension; lifespan; longevity; metabolism
    DOI:  https://doi.org/10.3390/biom14080940
  34. Exp Gerontol. 2024 Aug 23. pii: S0531-5565(24)00205-5. [Epub ahead of print] 112559
    Role of fibroblast autophagy and proliferation in skin anti-aging.
    Yantong Lu, Guangjuan Pan, Zhiying Wei, Yaohua Li, Xiaojiao Pan.
      Skin, as the outermost protective barrier of the body, becomes damaged with age and exposure to external stimuli. Dermal fibroblasts age and undergo apoptosis, which decreases collagen, collagen fibers, elastic fibers, hyaluronic acid, etc., leading skin to loss of elasticity and appearance of wrinkles. Skin aging is complex, involving several biological reactions，and various treatment methods are used to treat it. This review focuses on the importance of autophagy and cell proliferation in skin anti-aging, summarizes research progress on skin anti-aging by regulating autophagy and promoting the proliferation of dermal fibroblasts, and discusses future directions on skin anti-aging research.
    Keywords:  Autophagy; Cell proliferation; Dermis; Fibroblasts; Skin anti-aging
    DOI:  https://doi.org/10.1016/j.exger.2024.112559
  35. J Cachexia Sarcopenia Muscle. 2024 Aug 27.
    TRIM16 facilitates SIRT-1-dependent regulation of antioxidant response to alleviate age-related sarcopenia.
    Ai Guo, Ke Huang, Quanyi Lu, Bailong Tao, Kai Li, Dianming Jiang.
      BACKGROUND: Age-related sarcopenia, characterized by reduced skeletal muscle mass and function, significantly affects the health of the elderly individuals. Oxidative stress plays a crucial role in the development of sarcopenia. Tripartite motif containing 16 (TRIM16) is implicated in orchestrating antioxidant responses to mitigate oxidative stress, yet its regulatory role in skeletal muscle remains unclear. This study aims to elucidate the impact of TRIM16 on enhancing antioxidant response through SIRT-1, consequently mitigating age-related oxidative stress, and ameliorating muscle atrophy.METHODS: Aged mouse models were established utilizing male mice at 18 months with D-galactose (D-gal, 200 mg/kg) intervention and at 24 months with natural aging, while 3-month-old young mice served as controls. Muscle cell senescence was induced in C2C12 myoblasts using 30 g/L D-gal. TRIM16 was overexpressed in the skeletal muscle of aged mice and silenced/overexpressed in C2C12 myoblasts. The effects of TRIM16 on skeletal muscle mass, grip strength, morphological changes, myotube formation, myogenic differentiation, and muscle atrophy indicators were evaluated. Reactive oxygen species (ROS) levels and oxidative stress-related parameters were measured. The SIRT-1 inhibitor EX-527 was employed to elucidate the protective role of TRIM16 mediated through SIRT-1.
    RESULTS: Aged mice displayed significant reductions in lean mass (-11.58%; -14.47% vs. young, P < 0.05), hindlimb lean mass (-17.38%; -15.95% vs. young, P < 0.05), and grip strength (-22.29%; -31.45% vs. young, P < 0.01). Skeletal muscle fibre cross-sectional area (CSA) decreased (-29.30%; -24.12% vs. young, P < 0.05). TRIM16 expression significantly decreased in aging skeletal muscle (-56.82%; -66.27% vs. young, P < 0.001) and senescent muscle cells (-46.53% vs. control, P < 0.001). ROS levels increased (+69.83% vs. control, P < 0.001), and myotube formation decreased in senescent muscle cells (-56.68% vs. control, P < 0.001). Expression of myogenic differentiation and antioxidant indicators decreased, while muscle atrophy markers increased in vivo and in vitro (all P < 0.05). Silencing TRIM16 in myoblasts induced oxidative stress and myotube atrophy, while TRIM16 overexpression partially mitigated aging effects on skeletal muscle. TRIM16 activation enhanced SIRT-1 expression (+75.38% vs. control, P < 0.001). SIRT-1 inhibitor EX-527 (100 μM) suppressed TRIM16's antioxidant response and mitigating muscle atrophy, offsetting the protective effect of TRIM16 on senescent muscle cells.
    CONCLUSIONS: This study elucidates TRIM16's role in mitigating oxidative stress and ameliorating muscle atrophy through the activation of SIRT-1-dependent antioxidant effects. TRIM16 emerges as a potential therapeutic target for age-related sarcopenia.
    Keywords:  Muscle atrophy; Oxidative stress; Sarcopenia; TRIM16
    DOI:  https://doi.org/10.1002/jcsm.13553
  36. Biosensors (Basel). 2024 Aug 22. pii: 407. [Epub ahead of print]14(8):
    Recent Advances in Nanomaterials for Modulation of Stem Cell Differentiation and Its Therapeutic Applications.
    Chang-Dae Kim, Kyeong-Mo Koo, Hyung-Joo Kim, Tae-Hyung Kim.
      Challenges in directed differentiation and survival limit the clinical use of stem cells despite their promising therapeutic potential in regenerative medicine. Nanotechnology has emerged as a powerful tool to address these challenges and enable precise control over stem cell fate. In particular, nanomaterials can mimic an extracellular matrix and provide specific cues to guide stem cell differentiation and proliferation in the field of nanotechnology. For instance, recent studies have demonstrated that nanostructured surfaces and scaffolds can enhance stem cell lineage commitment modulated by intracellular regulation and external stimulation, such as reactive oxygen species (ROS) scavenging, autophagy, or electrical stimulation. Furthermore, nanoframework-based and upconversion nanoparticles can be used to deliver bioactive molecules, growth factors, and genetic materials to facilitate stem cell differentiation and tissue regeneration. The increasing use of nanostructures in stem cell research has led to the development of new therapeutic approaches. Therefore, this review provides an overview of recent advances in nanomaterials for modulating stem cell differentiation, including metal-, carbon-, and peptide-based strategies. In addition, we highlight the potential of these nano-enabled technologies for clinical applications of stem cell therapy by focusing on improving the differentiation efficiency and therapeutics. We believe that this review will inspire researchers to intensify their efforts and deepen their understanding, thereby accelerating the development of stem cell differentiation modulation, therapeutic applications in the pharmaceutical industry, and stem cell therapeutics.
    Keywords:  cellular adhesion; external stimulation; intracellular regulation; nanomaterials; stem cell differentiation
    DOI:  https://doi.org/10.3390/bios14080407
  37. Int J Mol Sci. 2024 Aug 08. pii: 8646. [Epub ahead of print]25(16):
    Effects of PCNA Stability on the Formation of Mutations.
    Matan Arbel-Groissman, Batia Liefshitz, Martin Kupiec.
      The fidelity of replication, especially in the presence of DNA damage, is essential for the proper function of cells. Mutations that inactivate genes involved in DNA damage repair or bypass are enriched in several types of cancer cells. Thus, it is important to further our understanding of the mechanisms governing replication fidelity. PCNA is a ring-shaped complex that encircles DNA at the front of the replication fork, at the double-stranded/single-stranded DNA junction. It serves as a processivity factor for the different DNA replication polymerases, allowing them to replicate longer stretches of DNA by physically tethering them to the DNA and preventing their detachment. In addition, PCNA also regulates and coordinates different DNA damage bypass pathways meant to allow DNA replication in the presence of DNA damage. Due to its essentiality and the numerous functions it has in the cell, much is still unclear about PCNA. Here, we utilize PCNA mutants that lower the stability of the PCNA complex on the chromatin, and thus tend to disassociate and fall from the DNA. Using these mutants, we show that PCNA's physical presence on the DNA can prevent DNA misalignment at repetitive sequences, leading to increased mutation formation. We also show that PCNA-interacting proteins play an important role in strengthening the ring's stability on the chromatin. Such repetitive sequence-induced mutations are common in several human diseases and it is important to study their formation and the mechanisms guarding against them.
    Keywords:  DNA Damage Tolerance; DNA repair; DNA replication; Saccharomyces cerevisiae; damage avoidance; mutagenesis; trans-lesion synthesis; yeast
    DOI:  https://doi.org/10.3390/ijms25168646
  38. Phytomedicine. 2024 Aug 17. pii: S0944-7113(24)00619-6. [Epub ahead of print]134 155961
    Exploring the anti-ovarian aging mechanism of He's Yangchao formula: Insights from multi-omics analysis in naturally aged mice.
    Liuqing Yang, Xinle Lai, Shuo Jin, Heng Wang, Fangxuan Lin, Xin Jin, Yun Chen, Ruye Wang, Yun Huang, Yiqun Zhang, Saisai Tian, Xiaohong Fang, Xing Duan, Qin Zhang.
      BACKGROUND: The rapid acceleration of female reproductive aging has become a major public health concern. He's Yangchao formula (HSYC), a compound comprising eight herbs, has demonstrated efficacy in enhancing ovarian function. Thus, an in-depth study of its anti-ovarian aging mechanism is required.PURPOSE: To evaluate the anti-ovarian aging effect of HSYC in naturally aged mice and investigate the underlying mechanism by analyzing the gut microbiota (GM), metabolome, and transcriptome.
    METHODS: Young and advanced maternal age (AMA) mice were selected for this study. Hematoxylin and eosin staining, fluorescence staining, western blotting, and qPCR analyses were used to detect the phenotypes associated with ovarian aging. Subsequently, analyses of the GM, transcriptome, and metabolome analyses were performed to explore the potential mechanisms of action of HSYC. Finally, in vivo and in vitro experiments were performed to verify potential therapeutic mechanisms.
    RESULTS: HSYC promoted follicular development in AMA mice and ameliorated age-related mitochondrial dysfunction, apoptosis, and defects in DNA damage repair. GM analysis revealed that HSYC treatment significantly increased the abundance of Akkermansia and Turicibacter. Transcriptome and metabolome analyses showed that HSYC might mitigate ovarian aging by regulating metabolic pathways, amino acid metabolism, glutathione metabolism, and the synthesis of pantothenic acid and coenzyme A. Combined transcriptomic and metabolomic analyses identified the glutathione metabolic pathway as the key pathway through which HSYC counteracts ovarian aging. Additional experimental verification confirmed that HSYC upregulated the glutathione metabolic genes GPX8, GSTA1, and GSTA4, increased glutathione-related products (GSH), and reduced ROS levels.
    CONCLUSIONS: HSYC exerts beneficial therapeutic effects on ovarian aging by regulating multiple endogenous metabolites, targets, and metabolic pathways, with an emphasis on its anti-ovarian aging effects through the glutathione metabolic pathway. These findings underscore the innovative potential of HSYC in addressing ovarian aging and offer a novel therapeutic approach that targets multiple biological pathways to improve the reproductive health of women with AMA..
    Keywords:  Multi-omics analysis; Reproduction age; Traditional Chinese medicine; glutathione metabolic pathway
    DOI:  https://doi.org/10.1016/j.phymed.2024.155961
  39. Cells. 2024 Aug 13. pii: 1345. [Epub ahead of print]13(16):
    Regulatory Effects of Senescent Mesenchymal Stem Cells: Endotheliocyte Reaction.
    Andrey Ratushnyy, Mariia Ezdakova, Diana Matveeva, Ekaterina Tyrina, Ludmila Buravkova.
      Currently, there is a growing focus on aging and age-related diseases. The processes of aging are based on cell senescence, which results in changes in intercellular communications and pathological alterations in tissues. In the present study, we investigate the influence of senescent mesenchymal stem cells (MSCs) on endothelial cells (ECs). In order to induce senescence in MSCs, we employed a method of stress-induced senescence utilizing mitomycin C (MmC). Subsequent experiments involved the interaction of ECs with MSCs in a coculture or the treatment of ECs with the secretome of senescent MSCs. After 48 h, we assessed the EC state. Our findings revealed that direct interaction led to a decrease in EC proliferation and migratory activity of the coculture. Furthermore, there was an increase in the activity of the lysosomal compartment, as well as an upregulation of the genes P21, IL6, IL8, ITGA1, and ITGB1. Treatment of ECs with the "senescent" secretome resulted in less pronounced effects, although a decrease in proliferation and an increase in ICAM-1 expression were observed. The maintenance of high levels of typical "senescent" cytokines and growth factors after 48 h suggests that the addition of the "senescent" secretome may have a prolonged effect on the cells. It is noteworthy that in samples treated with the "senescent" secretome, the level of PDGF-AA was higher, which may explain some of the pro-regenerative effects of senescent cells. Therefore, the detected changes may underlie both the negative and positive effects of senescence. The findings provide insight into the effects of cell senescence in vitro, where many of the organism's regulatory mechanisms are absent.
    Keywords:  ASC52telo; SASP; endothelial cells (ECs); mesenchymal stem cells (MSCs); mitomycin C (MmC); senescence
    DOI:  https://doi.org/10.3390/cells13161345
  40. bioRxiv. 2024 Aug 13. pii: 2024.08.12.607648. [Epub ahead of print]
    Serotonin neuromodulation directs optic nerve regeneration.
    Kristian Saied-Santiago, Melissa Baxter, Jaffna Mathiaparanam, Michael Granato.
      Optic nerve (ON) regeneration in mammalian systems is limited by an overshadowing dominance of inhibitory factors. This has severely hampered the identification of pro-regenerative pathways. Here, we take advantage of the regenerative capacity of larval zebrafish to identify pathways that promote ON regeneration. From a small molecule screen, we identified modulators of serotonin (5-HT) signaling that inhibit ON regeneration. We find several serotonin type-1 receptor genes are expressed in RGC neurons during regeneration and that inhibiting 5-HT1 receptors or components of the 5-HT pathway selectively impedes ON regeneration. We show that 5-HT1 receptor signaling is dispensable during ON development yet is critical for regenerating axons to emerge from the injury site. Blocking 5-HT receptors once ON axons have crossed the chiasm does not inhibit regeneration, suggesting a selective role for 5-HT receptor signaling early during ON regeneration. Finally, we show that agonist-mediated activation of 5-HT1 receptors leads to enhanced and ectopic axonal regrowth. Combined, our results provide evidence for mechanisms through which serotonin-dependent neuromodulation directs ON regeneration in vivo.
    Keywords:  5HT; Serotonin; axon regeneration; optic nerve; zebrafish
    DOI:  https://doi.org/10.1101/2024.08.12.607648
  41. Antioxidants (Basel). 2024 Aug 21. pii: 1019. [Epub ahead of print]13(8):
    ARE/Nrf2 Transcription System Involved in Carotenoid, Polyphenol, and Estradiol Protection from Rotenone-Induced Mitochondrial Oxidative Stress in Dermal Fibroblasts.
    Aya Darawsha, Aviram Trachtenberg, Yoav Sharoni.
      Skin aging is associated with the increased production of mitochondrial reactive oxygen species (mtROS) due to mitochondrial dysfunction, and various phytonutrients and estrogens have been shown to improve skin health. Thus, the aim of the current study was to examine damage to dermal fibroblasts by chemically induced mitochondrial dysfunction and to study the mechanism of the protective effects of carotenoids, polyphenols, and estradiol. Rotenone, a Complex I inhibitor, caused mitochondrial dysfunction in human dermal fibroblasts, substantially reducing respiration and ATP levels, followed by increased mitochondrial and cytosolic ROS, which resulted in apoptotic cell death, an increased number of senescent cells, increased matrix metalloproteinase-1 (MMP1) secretion, and decreased collagen secretion. Pre-treatment with carotenoid-rich tomato extracts, rosemary extract, and estradiol reversed these effects. These protective effects can be partially explained by a cooperative activation of antioxidant response element (ARE/Nrf2) transcriptional activity by the protective compounds and rotenone, which led to the upregulation of antioxidant proteins such as NQO1. To determine if ARE/Nrf2 activity is crucial for cell protection, we inhibited it using the Nrf2 inhibitors ML385 and ochratoxin A. This inhibition markedly reduced the protective effects of the test compounds by diminishing their effect to reduce cytosolic ROS. Our study results indicate that phytonutrients and estradiol protect skin cells from damage caused by mtROS, and thus may delay skin cell senescence and improve skin health.
    Keywords:  antioxidant response element/Nrf2 (ARE/Nrf2); collagen; dermal fibroblasts; estradiol; matrix metalloproteinase (MMP); mitochondrial dysfunction; reactive oxygen species (ROS); rosemary extract; rotenone; tomato extract
    DOI:  https://doi.org/10.3390/antiox13081019
  42. Antioxidants (Basel). 2024 Jul 24. pii: 894. [Epub ahead of print]13(8):
    Synthesis, Characterization, and Evaluation of a Hindered Phenol-Linked Benzophenone Hybrid Compound as a Potential Polymer Anti-Aging Agent.
    Shenshuai Wang, Yingjie Huang, Weiye Sun, Xufeng Lin.
      Hindered phenol antioxidants and benzophenone UV absorbers are common polymer additives and often used in combination applications to enhance the anti-aging performance of polymer materials. This study primarily aims to incorporate hindered phenol and benzophenone structures into a single molecule to develop a multifunctional polymer additive with good anti-aging performance. Thus, a novel potential polymer anti-aging agent, namely 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid 3-(4-benzoyl-3-hydroxyphenoxy)propyl ester (3C), was synthesized using 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionic acid, 3-bromo-1-propanol, and 2,4-dihydroxybenzophenone as raw materials by two-step procedure. The structure of compound 3C was characterized by nuclear magnetic resonance (NMR), high-resolution mass spectrometry (HRMS), Fourier-transform infrared (FT-IR) spectroscopy, and X-ray single crystal diffraction. Its thermal stability and UV resistance were assessed using thermogravimetric analysis (TGA) and UV absorption spectroscopy (UV). The compound 3C as an additive was incorporated into the preparation of polyolefin elastomer (POE) films. The anti-aging performance of POE films was evaluated by measuring parameters such as oxidation induction time, melt flow index, transmittance, and infrared spectra of the artificially aged POE films. The results indicate that the compound 3C exhibits a promising anti-aging performance in both thermo-oxidative aging and ultraviolet aging tests of POE films and is a potential polymer anti-aging agent.
    Keywords:  UV absorber; anti-aging agent; antioxidant; benzophenone; hindered phenol
    DOI:  https://doi.org/10.3390/antiox13080894
  43. Int J Mol Sci. 2024 Aug 08. pii: 8676. [Epub ahead of print]25(16):
    mTOR and SGLT-2 Inhibitors: Their Synergistic Effect on Age-Related Processes.
    Dario Troise, Silvia Mercuri, Barbara Infante, Vincenzo Losappio, Luciana Cirolla, Giuseppe Stefano Netti, Elena Ranieri, Giovanni Stallone.
      The aging process contributes significantly to the onset of chronic diseases, which are the primary causes of global mortality, morbidity, and healthcare costs. Numerous studies have shown that the removal of senescent cells from tissues extends lifespan and reduces the occurrence of age-related diseases. Consequently, there is growing momentum in the development of drugs targeting these cells. Among them, mTOR and SGLT-2 inhibitors have garnered attention due to their diverse effects: mTOR inhibitors regulate cellular growth, metabolism, and immune responses, while SGLT-2 inhibitors regulate glucose reabsorption in the kidneys, resulting in various beneficial metabolic effects. Importantly, these drugs may act synergistically by influencing senescence processes and pathways. Although direct studies on the combined effects of mTOR inhibition and SGLT-2 inhibition on age-related processes are limited, this review aims to highlight the potential synergistic benefits of these drugs in targeting senescence.
    Keywords:  SGLT-2 inhibitors; aging; inflammaging; mTOR inhibitors; senescence; senomorphic compounds; senotherapeutic strategies
    DOI:  https://doi.org/10.3390/ijms25168676
  44. J Cachexia Sarcopenia Muscle. 2024 Aug 26.
    Betaine delays age-related muscle loss by mitigating Mss51-induced impairment in mitochondrial respiration via Yin Yang1.
    Si Chen, Tongtong He, Jiedong Chen, Dongsheng Wen, Chen Wang, Wenge Huang, Zhijun Yang, Mengtao Yang, Mengchu Li, Siyu Huang, Zihui Huang, Huilian Zhu.
      BACKGROUND: Mitochondrial dysfunction is one of the hallmarks of aging and a leading contributor to sarcopenia. Nutrients are essential for improving mitochondrial function and skeletal muscle health during the aging process. Betaine is a nutrient with potential muscle-preserving properties. However, whether and how betaine could regulate the mitochondria function in aging muscle are poorly understood. We aimed to explore the molecular target and underlying mechanism of betaine in attenuating the age-related mitochondrial dysfunction in skeletal muscle.METHODS: Young mice (YOU, 2 months), old mice (OLD, 15 months), and old mice with betaine treatment (BET, 15 months) were fed for 12 weeks. The effects of betaine on muscle mass, strength, function, and subcellular structure of muscle fibres were assessed. RNA sequencing (RNA-seq) was conducted to identify the molecular target of betaine. The impacts of betaine on mitochondrial-related molecules, superoxide accumulation, and oxidative respiration were examined using western blotting (WB), immunofluorescence (IF) and seahorse assay. The underlying mechanism of betaine regulation on the molecular target to maintain mitochondrial function was investigated by luciferase reporter assay, chromatin immunoprecipitation and electrophoretic mobility shift assay. Adenoassociated virus transfection, succinate dehydrogenase staining (SDH), and energy expenditure assessment were performed on 20-month-old mice for validating the mechanism in vivo.
    RESULTS: Betaine intervention demonstrated anti-aging effects on the muscle mass (P = 0.017), strength (P = 0.010), and running distance (P = 0.013). Mitochondrial-related markers (ATP5a, Sdha, and Uqcrc2) were 1.1- to 1.5-fold higher in BET than OLD (all P ≤ 0.036) with less wasted mitochondrial vacuoles accumulating in sarcomere. Bioinformatic analysis from RNA-seq displayed pathways related to mitochondrial respiration activity was higher enriched in BET group (NES = -0.87, FDR = 0.10). The quantitative real time PCR (qRT-PCR) revealed betaine significantly reduced the expression of a novel mitochondrial regulator, Mss51 (-24.9%, P = 0.002). In C2C12 cells, betaine restored the Mss51-mediated suppression in mitochondrial respiration proteins (all P ≤ 0.041), attenuated oxygen consumption impairment, and superoxide accumulation (by 20.7%, P = 0.001). Mechanically, betaine attenuated aging-induced repression in Yy1 mRNA expression (BET vs. OLD: 2.06 vs. 1.02, P = 0.009). Yy1 transcriptionally suppressed Mss51 mRNA expression both in vitro and in vivo. This contributed to the preservation of mitochondrial respiration, improvement for energy expenditure (P = 0.008), and delay of muscle loss during aging process.
    CONCLUSIONS: Altogether, betaine transcriptionally represses Mss51 via Yy1, improving age-related mitochondrial respiration in skeletal muscle. These findings suggest betaine holds promise as a dietary supplement to delay skeletal muscle degeneration and improve age-related mitochondrial diseases.
    Keywords:  Betaine; Mitochondrial dysfunction; Mss51; Muscle loss; Transcription factor; Yin yang1 (Yy1)
    DOI:  https://doi.org/10.1002/jcsm.13558
  45. J Funct Biomater. 2024 Jul 31. pii: 215. [Epub ahead of print]15(8):
    Osteogenic Protection against Fine Dust with Erucic Acid-Induced Exosomes.
    Hyunjung Kim, Boyong Kim.
      Fine dust causes various disorders, including cardiovascular, neurological, renal, reproductive, motor, systemic, respiratory, and cancerous diseases. Therefore, it is essential to study functional materials to prevent these issues. This study investigated the beneficial effects of erucic acid against fine dust using methods such as miRNA profiling, quantitative PCR, flow cytometry, ELISA, and Alizarin O staining. Erucic acid effectively suppresses inflammation and upregulates osteogenic activators in fibroblasts exposed to fine dust. Additionally, erucic acid-induced exosomes (EIEs) strongly counteract the negative effects of fine dust on osteocytic differentiation and inflammation. Despite fine dust exposure, EIEs promoted osteocytic differentiation in adipose-derived stem cells (ASCs) and enhanced osteogenesis and phagocytosis in macrophages. The significant upregulation of RunX2 and BMP7 by EIEs indicates its strong role in osteocytic differentiation and protection against the effects of fine dust. EIEs also boosts immune activity and acts as an osteogenic trigger for macrophages. MicroRNA profiling revealed that EIEs dramatically upregulated miRNAs, including hsa-miRNA-1301-3p, hsa-miRNA-1908-5p, hsa-miRNA-423-5p, and hsa-miRNA-122-5p, which are associated with osteogenic differentiation and immunity. Therefore, EIEs show potential as biomaterials to prevent environment-borne diseases.
    Keywords:  PM10; adipose-derived stem cells; erucic acid; macrophage; microvesicle
    DOI:  https://doi.org/10.3390/jfb15080215
  46. Redox Biol. 2024 Aug 22. pii: S2213-2317(24)00295-7. [Epub ahead of print]76 103317
    AQP1 differentially orchestrates endothelial cell senescence.
    Khatereh Shabanian, Taraneh Shabanian, Gergely Karsai, Luca Pontiggia, Francesco Paneni, Frank Ruschitzka, Jürg H Beer, Seyed Soheil Saeedi Saravi.
      Accumulation of senescent endothelial cells (ECs) with age is a pivotal driver of cardiovascular diseases in aging. However, little is known about the mechanisms and signaling pathways that regulate EC senescence. In this report, we delineate a previously unrecognized role of aquaporin 1 (AQP1) in orchestrating extracellular hydrogen peroxide (H2O2)-induced cellular senescence in aortic ECs. Our findings underscore AQP1's differential impact on senescence hallmarks, including cell-cycle arrest, senescence-associated secretory phenotype (SASP), and DNA damage responses, intricately regulating angiogenesis. In proliferating ECs, AQP1 is crucial for maintaining angiogenic capacity, whereas disruption of AQP1 induces morphological and mitochondrial alterations, culminating in senescence and impaired angiogenesis. Conversely, Aqp1 knockdown or selective blockade of AQP1 in senescent ECs rescues the excess H2O2-induced cellular senescence phenotype and metabolic dysfunction, thereby ameliorating intrinsic angiogenic incompetence. Mechanistically, AQP1 facilitates H2O2 transmembrane transport, exacerbating oxidant-sensitive kinases CaMKII-AMPK. This process suppresses HDAC4 translocation, consequently de-repressing Mef2A-eNOS signaling in proliferating ECs. However, in senescent ECs, AQP1 overexpression is linked to preserved HDAC4-Mef2A complex and downregulation of eNOS signaling. Together, our studies identify AQP1 as a novel epigenetic regulator of HDAC4-Mef2A-dependent EC senescence and angiogenic potential, highlighting its potential as a therapeutic target for antagonizing age-related cardiovascular diseases.
    Keywords:  Aging; Angiogenesis; Aquaporin 1; Endothelial senescence; Epigenetic modification; Hydrogen peroxide
    DOI:  https://doi.org/10.1016/j.redox.2024.103317
  47. Cells. 2024 Aug 15. pii: 1361. [Epub ahead of print]13(16):
    Innovative Tools for DNA Topology Probing in Human Cells Reveal a Build-Up of Positive Supercoils Following Replication Stress at Telomeres and at the FRA3B Fragile Site.
    Claire Ghilain, Olivia Vidal-Cruchez, Aurélia Joly, Michelle Debatisse, Eric Gilson, Marie-Josèphe Giraud-Panis.
      Linear unconstrained DNA cannot harbor supercoils since these supercoils can diffuse and be eliminated by free rotation of the DNA strands at the end of the molecule. Mammalian telomeres, despite constituting the ends of linear chromosomes, can hold supercoils and be subjected to topological stress. While negative supercoiling was previously observed, thus proving the existence of telomeric topological constraints, positive supercoils were never probed due to the lack of an appropriate tool. Indeed, the few tools available currently could only investigate unwound (Trioxsalen) or overwound (GapR) DNA topology (variations in twist) but not the variations in writhe (supercoils and plectonemes). To address this question, we have designed innovative tools aimed at analyzing both positive and negative DNA writhe in cells. Using them, we could observe the build-up of positive supercoils following replication stress and inhibition of Topoisomerase 2 on telomeres. TRF2 depletion caused both telomere relaxation and an increase in positive supercoils while the inhibition of Histone Deacetylase I and II by TSA only caused telomere relaxation. Moving outside telomeres, we also observed a build-up of positive supercoils on the FRA3B fragile site following replication stress, suggesting a topological model of DNA fragility for this site.
    Keywords:  DNA topology; TRF2; telomere
    DOI:  https://doi.org/10.3390/cells13161361
  48. Phytomedicine. 2024 Aug 22. pii: S0944-7113(24)00629-9. [Epub ahead of print]134 155971
    Punica granatum L. leaf extract enhances stress tolerance and promotes healthy longevity through HLH-30/TFEB, DAF16/FOXO, and SKN1/NRF2 crosstalk in Caenorhabditis elegans.
    Monika N Todorova, Martina S Savova, Liliya V Mihaylova, Milen I Georgiev.
      BACKGROUND: Punica granatum L., commonly known as pomegranate, is renowned for its health benefits, primarily associated with the consumption of its fruit and seeds. However, its non-edible parts, including leaves, have been used in traditional medicine as a remedy with anti-inflammatory and anti-diabetic properties. Considering the abundance of bioactive compounds, predominantly flavonols, flavones, and tannins P. granatum leaf (PGL) extract holds potential as health-promoting agent. Yet, its effect on longevity and healthspan remains largely unexplored.PURPOSE: Our study aims to explore the potential of PGL extract to enhance healthspan and ameliorate age-related frailty in Caenorhabditis elegans. Additionally, we seek to elucidate its effect on the molecular signaling networks associated with stress resistance and longevity.
    METHODS: After characterizing the extract metabolite profile by NMR spectroscopy, phenotypic and stress analyses were performed. In order to establish the molecular mechanism of action, the involvement of signaling pathways key to longevity were investigated by means of real-time quantitative PCR (RT-qPCR) and the use of transgenic strains (MIR13, MAH240, LD1, and OH16024). In addition, the effect of PGL on metabolism and lipid accumulation, as well as mitochondrial homeostasis, was examined.
    RESULTS: The PGL extract supplementation significantly enhanced stress resistance and extended the lifespan of C. elegans. Additionally, it improved locomotion, as well as metabolic and mitochondrial functions, indicating an overall improvement in health. The molecular mechanisms highlight the coordinated regulation of stress response, metabolic homeostasis, and longevity signaling pathways. Specifically, our results demonstrate the essential roles of HLH-30/TFEB, in conjunction with DAF-16/FOXO and SKN-1/NRF2, as mediators of the PGL extract effect on healthspan.
    CONCLUSION: Our findings emphasize the potential of PGL extract to ameliorate age-related decline, induce longevity and further enhance healthspan. Given the diverse effects on the molecular network associated with stress-adaptations, longevity and metabolic control, PGL extract might become a promising natural product with a particular importance to the field of gerontology.
    Keywords:  Aging; Caenorhabditis elegans; Healthspan; Longevity; Pomegranate; Punica granatum
    DOI:  https://doi.org/10.1016/j.phymed.2024.155971
  49. Clin Nutr. 2024 Aug 18. pii: S0261-5614(24)00290-5. [Epub ahead of print]43(10): 2236-2248
    Western diet-induced cognitive and metabolic dysfunctions in aged mice are prevented by rosmarinic acid in a sex-dependent fashion.
    Letizia Giona, Chiara Musillo, Gaia De Cristofaro, Michael Ristow, Kim Zarse, Karsten Siems, Sabrina Tait, Francesca Cirulli, Alessandra Berry.
      BACKGROUND & AIMS: Unhealthy lifestyles, such as chronic consumption of a Western Diet (WD), have been associated with increased systemic inflammation and oxidative stress (OS), a condition that may favour cognitive dysfunctions during aging. Polyphenols, such as rosmarinic acid (RA) may buffer low-grade inflammation and OS, characterizing the aging brain that is sustained by WD, promoting healthspan. The aim of this study was to evaluate the ability of RA to prevent cognitive decline in a mouse model of WD-driven unhealthy aging and to gain knowledge on the specific molecular pathways modulated within the brain.METHODS: Aged male and female C57Bl/6N mice were supplemented either with RA or vehicle for 6 weeks. Following 2 weeks on RA they started being administered either with WD or control diet (CD). Successively all mice were tested for cognitive abilities in the Morris water maze (MWM) and emotionality in the elevated plus maze (EPM). Glucose and lipid homeostasis were assessed in trunk blood while the hippocampus was dissected out for RNAseq transcriptomic analysis.
    RESULTS: RA prevented insulin resistance in males while protecting both males and females from WD-dependent memory impairment. In the hippocampus, RA modulated OS pathways in males and immune- and sex hormones-related signalling cascades (Lhb and Lhcgr genes) in females. Moreover, RA overall resulted in an upregulation of Glp1r, recently identified as a promising target to prevent metabolic derangements. In addition, we also found an RA-dependent enrichment in nuclear transcription factors, such as NF-κB, GR and STAT3, that have been recently suggested to promote healthspan and longevity by modulating inflammatory and cell survival pathways.
    CONCLUSIONS: Oral RA supplementation may promote brain and metabolic plasticity during aging through antioxidant and immune-modulating properties possibly affecting the post-reproductive hormonal milieu in a sex-dependent fashion. Thus, its supplementation should be considered in the context of precision medicine as a possible strategy to preserve cognitive functions and to counteract metabolic derangements.
    Keywords:  Aging; Cognitive dysfunction; Metabolic syndrome; Mouse; Rosmarinic acid; Sex differences
    DOI:  https://doi.org/10.1016/j.clnu.2024.08.012
  50. Am J Physiol Endocrinol Metab. 2024 Aug 28.
    Secreted GDF15 maintains transcriptional responses during DNA damage-mediated senescence in human β-cells.
    Nayara Rampazzo Morelli, Camille Préfontaine, Jasmine Pipella, Peter J Thompson.
      Type 1 Diabetes (T1D) is a chronic metabolic disease resulting from autoimmune destruction of pancreatic beta cells. Beta cells activate a variety of stress responses during the development of T1D, including senescence, which involves cell cycle arrest, prosurvival signaling and a proinflammatory secretome termed the senescence-associated secretory phenotype (SASP). We previously identified growth and differentiation factor 15 (GDF15) as a major SASP factor in human islets and human EndoC-βH5 beta cells in a model of DNA damage-mediated senescence that recapitulates features of senescent beta cells in T1D. Soluble GDF15 has been shown to exert protective effects on human and mouse beta cells during various forms of stress relevant to T1D, therefore we hypothesized that secreted GDF15 may play a prosurvival role during DNA damage-mediated senescence in human beta cells. We found that elevated GDF15 secretion was associated with endogenous senescent beta cells in an islet preparation from a T1D donor, supporting the validity of our DNA damage model. Using antibody-based neutralization, we found that secreted endogenous GDF15 was not required for senescent human islet or EndoC cell viability. Rather, neutralization of GDF15 led to reduced expression of specific senescence-associated genes, including GDF15 itself and the prosurvival gene BCL2L1. Taken together, these data suggest that SASP factor GDF15 is not required to sustain senescent human islet viability, but it is required to maintain senescence-associated transcriptional responses.
    Keywords:  Cellular senescence; DNA damage response; GDF15; Pancreatic beta cells; Senescence associated secretory phenotype
    DOI:  https://doi.org/10.1152/ajpendo.00257.2024
  51. Aging Cell. 2024 Aug 27. e14272
    The NLRP3 inhibitor Dapansutrile improves the therapeutic action of lonafarnib on progeroid mice.
    Inés Muela-Zarzuela, Juan Miguel Suarez-Rivero, Daniel Boy-Ruiz, Juan López-Pérez, Marta Sotelo-Montoro, Maria Del Mar Navarrete-Alonso, Isidro G Collado, José Manuel Botubol-Ares, Alberto Sanz, Mario D Cordero.
      The role of the inflammasomes in aging and progeroid syndromes remain understudied. Recently, MCC950, a NLRP3 inhibitor, was used in Zmpste24-/- mice to ameliorate the phenotypes. However, the safety of MCC950 was questioned due to liver toxicity observed in humans. Nevertheless, inhibition of the inflammasomes would be a beneficial therapy for progeria. Here, we show that OLT1177 (dapansutrile), other NLRP3 inhibitor, improved cellular and animal phenotypes using progeroid fibroblasts and a LmnaG609G/G609G mouse model. In both cases dapansutrile reduced progerin accumulation, NLRP3-inflammasome activation and secretory phenotype of senescence, extended the lifespan of progeroid animals, preserved bodyweight, and reduced kyphosis, inflammation, and senescence. Interestingly, dapansutrile further improved the effect of lonafarnib, the only FDA-approved drug for the progeria. The combination of both drugs reduced the inflammation and senescence, extended survival and ameliorated various progeroid defects both in vitro and in vivo, compared with treatment using lonafarnib alone. These findings and the safety of dapansutrile demonstrated in several clinical trials proposes it as a possible co-adjuvant treatment with lonafarnid in HGPS.
    Keywords:  Dapansutrile; Lonafarnib; NLRP3; progeria
    DOI:  https://doi.org/10.1111/acel.14272
  52. Antioxidants (Basel). 2024 Aug 08. pii: 964. [Epub ahead of print]13(8):
    Antioxidant Potential of Exosomes in Animal Nutrition.
    Hengyu Jin, Jianxin Liu, Diming Wang.
      This review delves into the advantages of exosomes as novel antioxidants in animal nutrition and their potential for regulating oxidative stress. Although traditional nutritional approaches promote oxidative stress defense systems in mammalian animals, several issues remain to be solved, such as low bioavailability, targeted tissue efficiency, and high-dose by-effect. As an important candidate offering regulation opportunities concerned with cellular communication, disease prevention, and physiology regulation in multiple biological systems, the potential of exosomes in mediating redox status in biological systems has not been well described. A previously reported relationship between redox system regulation and circulating exosomes suggested exosomes as a fundamental candidate for both a regulator and biomarker for a redox system. Herein, we review the effects of oxidative stress on exosomes in animals and the potential application of exosomes as antioxidants in animal nutrition. Then, we highlight the advantages of exosomes as redox regulators due to their higher bioavailability and physiological heterogeneity-targeted properties, providing a theoretical foundation and feed industry application. Therefore, exosomes have shown great potential as novel antioxidants in the field of animal nutrition. They can overcome the limitations of traditional antioxidants in terms of dosage and side effects, which will provide unprecedented opportunities in nutritional management and disease prevention, and may become a major breakthrough in the field of animal nutrition.
    Keywords:  animal nutrition; antioxidants; exosome; milk exosome; oxidative stress
    DOI:  https://doi.org/10.3390/antiox13080964
  53. Nat Aging. 2024 Aug 28.
    Author Correction: Rare genetic coding variants associated with human longevity and protection against age-related diseases.
    Regeneron Genetics Center
      
    DOI:  https://doi.org/10.1038/s43587-024-00708-x
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