bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–01–05
thirty papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Yoga and Telomeres: A Path to Cellular Longevity?
  2. The aldose reductase inhibitors AT-001, AT-003 and AT-007 attenuate human keratinocyte senescence.
  3. Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice.
  4. Basic Science and Pathogenesis.
  5. Alpha-Glucosidase Inhibitors in Aging and Aging-Related Diseases: Clinical Applications and Relevant Mechanisms.
  6. Epigenetic Clocks: Beyond Biological Age, Using the Past to Predict the Present and Future.
  7. The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk.
  8. Critical review of aging clocks and factors that may influence the pace of aging.
  9. BayesAge 2.0: a maximum likelihood algorithm to predict transcriptomic age.
  10. Basic Science and Pathogenesis.
  11. Comparison of age-related decline in C57BL/6J and CB6F1J male mice.
  12. A microbiota-derived metabolite, 3-phenyllactic acid, prolongs healthspan by enhancing mitochondrial function and stress resilience via SKN-1/ATFS-1 in C. elegans.
  13. Structural characterization and anti-aging activity investigation of a polysaccharide from Anemarrhena asphodeloides Bge.
  14. The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.
  15. Multi-omics approach reveals TGF-β signaling-driven senescence in periodontium stem cells.
  16. A machine learning approach identifies cellular senescence on transcriptome data of human cells in vitro.
  17. Tgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation to Promote SASP in Senescent Microglia.
  18. The A-Z of age-related dermatological diseases.
  19. Revisiting the Benefits of Exercise for Alzheimer's Disease through the Lens of Ferroptosis: A New Perspective.
  20. Curcumin liposomes alleviate senescence of bone marrow mesenchymal stem cells by activating mitophagy.
  21. Stability and antioxidant function of Porphyra haitanensis proteins during simulated gastrointestinal digestion: Effects on stress resistance and lifespan extension in Caenorhabditis elegans.
  22. Senescent Macrophages and the Lung Cancer Microenvironment: A New Perspective on Tumor Immune Evasion.
  23. Histone mark age of human tissues and cell types.
  24. Inactivation of the SLC25A1 gene during embryogenesis induces a unique senescence program controlled by p53.
  25. The effects of high-intensity interval training on cognitive performance: a systematic review and meta-analysis.
  26. A brief report on biomarkers of cellular senescence associated with liver frailty and length of stay in liver transplantation.
  27. CREG1 attenuates intervertebral disc degeneration by alleviating nucleus pulposus cell pyroptosis via the PINK1/Parkin-related mitophagy pathway.
  28. Astragaloside IV confers neuroprotection against radiation-induced neuronal senescence via the ERK pathway.
  29. Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons.
  30. Anti-angiogenic activity and mechanism of fucoidan from brown algae, Sargassum Naozhouense mediated by intracellular antioxidation.
  1. Cureus. 2024 Nov;16(11): e74552
    Yoga and Telomeres: A Path to Cellular Longevity?
    Selvaraj Giridharan.
      Telomeres, which protect the chromosomal ends, are vital for cellular senescence and health. Telomere shortening, often due to stress, inflammation, and oxidative damage, is linked to age-related diseases such as cancer, cardiovascular issues, and neurodegeneration. Evidence suggests that meditation may affect telomere dynamics by reducing stress and inflammation and improving emotional regulation. Clinical trials have demonstrated that the effectiveness of these practices in increasing telomerase activity and maintaining telomere length varies by type, intensity, and duration of the practice. Yoga and meditation boost cellular resilience by lowering stress, inflammation, and oxidative damage and enhancing neuroendocrine regulation. Despite promising results, study design variability and limited long-term data require further research. Future studies should identify the most effective components, dose-response relationships, and long-term effects across populations. Increasing evidence suggests that yoga and meditation could be key preventive and therapeutic strategies to improve cellular health and longevity.
    Keywords:  longevity; meditation; telomerase; telomeres; yoga
    DOI:  https://doi.org/10.7759/cureus.74552
  2. Front Aging. 2024 ;5 1466281
    The aldose reductase inhibitors AT-001, AT-003 and AT-007 attenuate human keratinocyte senescence.
    Gautham Yepuri, Kushie Kancharla, Riccardo Perfetti, Shoshana Shendelman, Andrew Wasmuth, Ravichandran Ramasamy.
      Human skin plays an important role protecting the body from both extrinsic and intrinsic factors. Skin aging at cellular level, which is a consequence of accumulation of irreparable senescent keratinocytes is associated with chronological aging. However, cell senescence may occur independent of chronological aging and it may be accelerated by various pathological conditions. Recent studies have shown that oxidative stress driven keratinocyte senescence is linked to the rate limiting polyol pathway enzyme aldose reductase (AR). Here we investigated the role of three novel synthetic AR inhibitors (ARIs) AT-001, AT-003 and AT-007 in attenuating induced skin cell senescence, in primary normal human keratinocytes (NHK cells), using three different senescence inducing agents: high glucose (HG), hydrogen peroxide (H2O2) and mitomycin-c (MMC). To understand the efficacy of ARIs in reducing senescence, we have assessed markers of senescence, including SA-β-galactosidase activity, γ-H2AX foci, gene expression of CDKN1A, TP53 and SERPINE1, reactive oxygen species generation and senescence associated secretory phenotypes (SASP). Strikingly, all three ARIs significantly inhibited the assessed senescent markers, after senescence induction. Our data confirms the potential role of ARIs in reducing NHK cell senescence and paves the way for preclinical and clinical testing of these ARIs in attenuating cell aging and aging associated diseases.
    Keywords:  aldose reductase; aldose reductase inhibitors; oxidative stress; senescence; skin cell aging
    DOI:  https://doi.org/10.3389/fragi.2024.1466281
  3. Cell Res. 2025 Jan 02.
    Reducing functionally defective old HSCs alleviates aging-related phenotypes in old recipient mice.
    Yuting Wang, Wenhao Zhang, Chao Zhang, Hoang Q Tran Van, Takashi Seino, Yi Zhang.
      Aging is a process accompanied by functional decline in tissues and organs with great social and medical consequences. Developing effective anti-aging strategies is of great significance. In this study, we demonstrated that transplantation of young hematopoietic stem cells (HSCs) into old mice can mitigate aging phenotypes, underscoring the crucial role of HSCs in the aging process. Through comprehensive molecular and functional analyses, we identified a subset of HSCs in aged mice that exhibit "younger" molecular profiles and functions, marked by low levels of CD150 expression. Mechanistically, CD150low HSCs from old mice but not their CD150high counterparts can effectively differentiate into downstream lineage cells. Notably, transplantation of old CD150low HSCs attenuates aging phenotypes and prolongs lifespan of elderly mice compared to those transplanted with unselected or CD150high HSCs. Importantly, reducing the dysfunctional CD150high HSCs can alleviate aging phenotypes in old recipient mice. Thus, our study demonstrates the presence of "younger" HSCs in old mice, and that aging-associated functional decline can be mitigated by reducing dysfunctional HSCs.
    DOI:  https://doi.org/10.1038/s41422-024-01057-5
  4. Alzheimers Dement. 2024 Dec;20 Suppl 1 e083659
    Basic Science and Pathogenesis.
    Saul Villeda.
       BACKGROUND: Aging drives cellular and cognitive impairments in the adult brain. It is imperative to gain mechanistic insight into what drives aging phenotypes in the brain in order to maintain, and even restore, functional integrity in the elderly.
    METHOD: We, and others, have shown that systemic interventions - such as heterochronic parabiosis (in which a young and old circulatory system are joined) and administration of young blood or exercise induced blood factors - can reverse age-related impairments in regenerative, synaptic and inflammatory processes, as well as rescue cognitive faculties in the aged brain.
    RESULT: Rejuvenating systemic intervention studies have revealed an age-dependent bi-directionality in the influence of the systemic environment indicating pro-youthful trophic factors in young blood elicit rejuvenation while pro-aging immune factors in old blood drive aging.
    CONCLUSION: It has been proposed that introducing pro-youthful trophic factors or mitigating the effect of pro-aging immune factors may provide effective strategies to rejuvenate aging phenotypes in the brain. Despite this potential, much is unknown as to the systemic and molecular mechanisms regulating the effects of blood-borne factors. I will discuss work from my research group that begins to provide insight into the beneficial effects of targeting individual systemic immune factors and the downstream molecular drivers promoting rejuvenation in the aging brain.
    DOI:  https://doi.org/10.1002/alz.083659
  5. Aging Dis. 2025 Jan 02.
    Alpha-Glucosidase Inhibitors in Aging and Aging-Related Diseases: Clinical Applications and Relevant Mechanisms.
    Ling Zhong, Jielin Yang, Jibran Nehal Syed, Yuwei Zhang, Yan Tian, Xianghui Fu.
      Aging is a complex and universal process marked by gradual functional declines at the cellular and tissue levels, often leading to a range of aging-related diseases such as diabetes, cardiovascular diseases, and cancer. Delaying the aging process can help prevent, slow down, and alleviate the severity of these various conditions, enhancing overall health and well-being. Alpha-glucosidase inhibitors (AGIs) are a class of widely used antidiabetic drugs that inhibit alpha-glucosidase in the small intestinal mucosa, delaying carbohydrate absorption and reducing postprandial hyperglycemia. Beyond their roles in diabetes treatment, AGIs have shown potential in extending lifespan and effectively treating aging-related diseases by modulating oxidative stress, gut microbiota, inflammatory responses, and nutrient-sensing pathways. This review summarizes recent advancements in the application of AGIs for preventing and treating aging and aging-related diseases, with a focus on their mechanisms and roles in these processes.
    DOI:  https://doi.org/10.14336/AD.2024.1477
  6. Aging Dis. 2024 Dec 23.
    Epigenetic Clocks: Beyond Biological Age, Using the Past to Predict the Present and Future.
    Runyu Liang, Qiang Tang, Jia Chen, Luwen Zhu.
      Predicting health trajectories and accurately measuring aging processes across the human lifespan remain profound scientific challenges. Assessing the effectiveness and impact of interventions targeting aging is even more elusive, largely due to the intricate, multidimensional nature of aging-a process that defies simple quantification. Traditional biomarkers offer only partial perspectives, capturing limited aspects of the aging landscape. Yet, over the past decade, groundbreaking advancements have emerged. Epigenetic clocks, derived from DNA methylation patterns, have established themselves as powerful aging biomarkers, capable of estimating biological age and assessing aging rates across diverse tissues with remarkable precision. These clocks provide predictive insights into mortality and age-related disease risks, effectively distinguishing biological age from chronological age and illuminating enduring questions in gerontology. Despite significant progress in epigenetic clock development, substantial challenges remain, underscoring the need for continued investigation to fully unlock their potential in the science of aging.
    DOI:  https://doi.org/10.14336/AD.2024.1495
  7. Ageing Res Rev. 2024 Dec 31. pii: S1568-1637(24)00471-9. [Epub ahead of print] 102653
    The Immunosenescence Clock: A New Method for Evaluating Biological Age and Predicting Mortality Risk.
    Shuyu Li, Ke Wang, Jingni Wu, Yongliang Zhu.
      Precisely assessing an individual's immune age is critical for developing targeted aging interventions. Although traditional methods for evaluating biological age, such as the use of cellular senescence markers and physiological indicators, have been widely applied, these methods inherently struggle to capture the full complexity of biological aging. We propose the concept of an 'immunosenescence clock' that evaluates immune system changes on the basis of changes in immune cell abundance and omics data (including transcriptome and proteome data), providing a complementary indicator for understanding age-related physiological transformations. Rather than claiming to definitively measure biological age, this approach can be divided into a biological age prediction clock and a mortality prediction clock. The main function of the biological age prediction clock is to reflect the physiological state through the transcriptome data of peripheral blood mononuclear cells (PBMCs), whereas the mortality prediction clock emphasizes the ability to identify people at high risk of mortality and disease. We hereby present nearly all of the immunosenescence clocks developed to date, as well as their functional differences. Critically, we explicitly acknowledge that no single diagnostic test can exhaustively capture the intricate changes associated with biological aging. Furthermore, as these biological functions are based on the acceleration or delay of immunosenescence, we also summarize the factors that accelerate immunosenescence and the methods for delaying it. A deep understanding of the regulatory mechanisms of immunosenescence can help establish more accurate immune-age models, providing support for personalized longevity interventions and improving quality of life in old age.
    Keywords:  Aging; Biological age; Chronological age; Immunosenescence clocks; Mortality risk
    DOI:  https://doi.org/10.1016/j.arr.2024.102653
  8. Front Aging. 2024 ;5 1487260
    Critical review of aging clocks and factors that may influence the pace of aging.
    Mildred Min, Caitlin Egli, Ajay S Dulai, Raja K Sivamani.
       Background and objectives: Aging clocks are computational models designed to measure biological age and aging rate based on age-related markers including epigenetic, proteomic, and immunomic changes, gut and skin microbiota, among others. In this narrative review, we aim to discuss the currently available aging clocks, ranging from epigenetic aging clocks to visual skin aging clocks.
    Methods: We performed a literature search on PubMed/MEDLINE databases with keywords including: "aging clock," "aging," "biological age," "chronological age," "epigenetic," "proteomic," "microbiome," "telomere," "metabolic," "inflammation," "glycomic," "lifestyle," "nutrition," "diet," "exercise," "psychosocial," and "technology."
    Results: Notably, several CpG regions, plasma proteins, inflammatory and immune biomarkers, microbiome shifts, neuroimaging changes, and visual skin aging parameters demonstrated roles in aging and aging clock predictions. Further analysis on the most predictive CpGs and biomarkers is warranted. Limitations of aging clocks include technical noise which may be corrected with additional statistical techniques, and the diversity and applicability of samples utilized.
    Conclusion: Aging clocks have significant therapeutic potential to better understand aging and the influence of chronic inflammation and diseases in an expanding older population.
    Keywords:  PACE; aging; biological age; clock; epigenetic; microbiome; proteomic
    DOI:  https://doi.org/10.3389/fragi.2024.1487260
  9. Geroscience. 2025 Jan 03.
    BayesAge 2.0: a maximum likelihood algorithm to predict transcriptomic age.
    Lajoyce Mboning, Emma K Costa, Jingxun Chen, Louis-S Bouchard, Matteo Pellegrini.
      Aging is a complex biological process influenced by various factors, including genetic and environmental influences. In this study, we present BayesAge 2.0, an upgraded version of our maximum likelihood algorithm designed for predicting transcriptomic age (tAge) from RNA-seq data. Building on the original BayesAge framework, which was developed for epigenetic age prediction, BayesAge 2.0 integrates a Poisson distribution to model count-based gene expression data and employs LOWESS smoothing to capture nonlinear gene-age relationships. BayesAge 2.0 provides significant improvements over traditional linear models, such as Elastic Net regression. Specifically, it addresses issues of age bias in predictions, with minimal age-associated bias observed in residuals. Its computational efficiency further distinguishes it from traditional models, as reference construction and cross-validation are completed more quickly compared to Elastic Net regression, which requires extensive hyperparameter tuning. Overall, BayesAge 2.0 represents a step forward in tAge prediction, offering a robust, accurate, and efficient tool for aging research and biomarker development.
    Keywords:  Aging clocks; BayesAge; Elastic Net regression; Epigenetic age; Transcriptomic age; tAge
    DOI:  https://doi.org/10.1007/s11357-024-01499-0
  10. Alzheimers Dement. 2024 Dec;20 Suppl 1 e090422
    Basic Science and Pathogenesis.
    Shiva Kazempour Dehkordi, Habil Zare, Miranda E Orr.
       BACKGROUND: Cellular senescence, which can cause significant changes in morphology, metabolism, and function, is a key contributor to aging and diseases including Alzheimer's Disease (AD). Accurate biomarker identification is essential for detecting senescent cells. Our research aims at defining gene signatures that encapsulate senescence complexity in the brain. Our previous study, highlighted CDKN2D/p19 as a reliable senescence marker in tau neuropathology. This study advances our approach using a new snRNA-Seq dataset.
    METHOD: We evaluated snRNA-Seq data from 92 postmortem brains (PMID: 37774680) to validate senescent cell types, utilizing the transcriptional profiles of around 414,000 cells. We used an eigengene-based approach, where an eigengene is a weighted average expression of genes that summarizes biological signatures with minimal loss of information (PMID: 28298217). Using established weightings from our prior research (PMID: 35531351), we inferred eigengenes indicative of senescence in this dataset. We also recalculated eigengenes for key senescence pathways - the canonical senescence pathway (CSP) which reflects cell cycle arrest, the senescence initiator pathway (SIP) indicating cellular damage and stress, and the senescence response pathway (SRP) representing the toxic senescence-associated secretory phenotype (SASP) - and assessed the overlap of senescent cells using statistical tests.
    RESULT: Using eigengenes inferred from our previous study, we confirmed that excitatory neurons significantly expressed CSP and SIP signatures in the new dataset. Additionally, microglia and vascular cells in CSP, inhibitory neurons in SIP, and astrocytes and vascular cells in SRP showed significant enrichment (Fig. 1a-c). Recalculation of eigengenes supported these findings by returning the enrichment of exact cell types within each pathway, demonstrating the method's robustness in identifying senescent cell types. Furthermore, a substantial number of cells showed overlapping senescence signatures across the CSP, SIP, and SRP (Fig. 2), confirming consistency between inference and recalculated eigengenes.
    CONCLUSION: Our findings validate a computational strategy for detecting senescent cells via eigengene analysis. Consistent identification of senescent cell signatures between inferred and recalculated eigengenes across neural and vascular cells confirms the accuracy of our methods. This approach may direct AD therapeutic development by pinpointing precise senescent cell targets, and uncover new biomarkers of brain cell senescence.
    DOI:  https://doi.org/10.1002/alz.090422
  11. PLoS One. 2024 ;19(12): e0306201
    Comparison of age-related decline in C57BL/6J and CB6F1J male mice.
    Gerald Yu Liao, Christina Pettan-Brewer, Warren Ladiges.
      Variability in physical resilience to aging prompts a comprehensive examination of underlying mechanisms across organs and individuals. We conducted a detailed exploration of behavioral and physiological differences between male C57BL/6J and male CB6F1J mice across various age groups (4, 12, 20, 24 months). In behavioral assays, C57BL/6J mice displayed superior performance in rotarod tasks but higher anxiety while CB6F1J mice exhibited a decline in short-term memory with age. Grip strength, long-term memory, and voluntary wheel running declined similarly with age in both strains. Examining physiological phenotypes, C57BL/6J mice exhibited lower body fat percentages across ages compared to CB6F1J mice, though cataract severity worsened with age in both strains. Analysis of cardiac functions revealed differences between strains, with worsening left ventricular hypertrophy and structural heart abnormalities with age in CB6F1J mice along with higher blood pressure than C57BL/6J. Lesion scores showed an age-related increase in heart, kidney, and liver lesions in both strains, while lung lesions worsened with age only in CB6F1J mice. This study underscores the validity of behavioral assays and geropathology assessment in reflecting age-related decline and emphasizes the importance of considering strain specificity when using mouse models to study human aging.
    DOI:  https://doi.org/10.1371/journal.pone.0306201
  12. Nat Commun. 2024 Dec 30. 15(1): 10773
    A microbiota-derived metabolite, 3-phenyllactic acid, prolongs healthspan by enhancing mitochondrial function and stress resilience via SKN-1/ATFS-1 in C. elegans.
    Juewon Kim, Yunju Jo, Gyumin Lim, Yosep Ji, Jong-Hwa Roh, Wan-Gi Kim, Hyon-Seung Yi, Dong Wook Choi, Donghyun Cho, Dongryeol Ryu.
      The mechanisms underlying the impact of probiotic supplementation on health remain largely elusive. While previous studies primarily focus on the discovery of novel bioactive bacteria and alterations in the microbiome environment to explain potential probiotic effects, our research delves into the role of living Lactiplantibacillus (formerly known as Lactobacillus) and their conditioned media, highlighting that only the former, not dead bacteria, enhance the healthspan of Caenorhabditis elegans (C. elegans). To elucidate the underlying mechanisms, we conduct transcriptomic profiling through RNA-seq analysis in C. elegans exposed to GTB1, a strain of Lactiplantibacillus plantarum or 3-phenyllactic acid (PLA), mimicking the presence of key candidate metabolites of GTB1 and evaluating healthspan. Our findings reveal that PLA treatment significantly extends the healthspan of C. elegans by promoting energy metabolism and stress resilience in a SKN-1/ATFS-1-dependent manner. Moreover, PLA-mediated longevity is associated with a novel age-related parameter, the Healthy Aging Index (HAI), introduced in this study, which comprises healthspan-related factors such as motility, oxygen consumption rate (OCR), and ATP levels. Extending the relevance of our work to humans, we observe an inverse correlation between blood PLA levels and physical performance in patients with sarcopenia, when compared to age-matched non-sarcopenic controls. Our investigation thus sheds light on the pivotal role of the metabolite PLA in probiotics-mediated enhancement of organismal healthspan, and also hints at its potential involvement in age-associated sarcopenia. These findings warrant further investigation to delineate PLA's role in mitigating age-related declines in healthspan and resilience to external stressors.
    DOI:  https://doi.org/10.1038/s41467-024-55015-1
  13. Int J Biol Macromol. 2024 Dec 27. pii: S0141-8130(24)10027-X. [Epub ahead of print] 139216
    Structural characterization and anti-aging activity investigation of a polysaccharide from Anemarrhena asphodeloides Bge.
    Xinxin Fan, Yu Lu, Yujun Xie, Xiaodong Yan, Wanyu Fan, Yuji Ishii, Boyang Yu, Renshi Li.
      Anemarrhena asphodeloides Bge. (AAB), a traditional medicinal herb, has a long history of delaying the aging process. Yet, the anti-aging effects of its polysaccharides have not been thoroughly investigated. This study marks the first exploration of the anti-aging activity of Anemarrhena asphodeloides Bge. polysaccharides (AABP). The MW of AABP-1a was determined to be 210.062 kDa, with a composition consisting predominantly of glucose and mannose in a molar ratio of approximately 4:1. The backbone of AABP-1a was mainly composed of →4)-2Ac-β-Man(1→ and →4)-β-Glc(1→ and a small amount of branched →4,6)-β-Glc(1→ and →3,4)-β-Glc(1→, the branching part was composed of →6)-β-Glc(1→ and t-α-Glc(1→. AABP-1a has antioxidant capacity and can improve cell cycle arrest mediated by senescence markers such as p53, p21, p16 and SASP, and reduce the accumulation of damaged DNA. In addition, it could reduce the activity of SA-β-Gal in zebrafish, prolong the lifespan of C. elegans and reduce the expression of lipofuscin. This study found a glucomannan and demonstrated its anti-aging activity in various aging models. These results provide a theoretical basis for further study of the anti-aging effect of AAB.
    Keywords:  Anemarrhena asphodeloides Bge. polysaccharides; Anti-aging; Multi-models; Structure characterization
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139216
  14. Sci Rep. 2024 Dec 30. 14(1): 31589
    The relationship between mitochondrial health, telomerase activity and longitudinal telomere attrition, considering the role of chronic stress.
    Mauricio Guillen-Parra, Jue Lin, Aric A Prather, Owen M Wolkowitz, Martin Picard, Elissa S Epel.
      Telomere attrition is a hallmark of biological aging, contributing to cellular replicative senescence. However, few studies have examined the determinants of telomere attrition in vivo in humans. Mitochondrial Health Index (MHI), a composite marker integrating mitochondrial energy-transformation capacity and content, may be one important mediator of telomere attrition, as it could impact telomerase activity, a direct regulator of telomere maintenance. In this observational longitudinal study, we examined in peripheral blood mononuclear cells (PBMCs), whether MHI predicted changes in telomerase activity over a 9-month period, thus impacting telomere maintenance over this same period of time. We secondarily examined the role of chronic stress, by comparing these relationships in mothers of children with an autism spectrum disorder (caregivers) vs. mothers of a neurotypical child (controls). Here we show that both chronic stress exposure and lower MHI independently predicted decreases in telomerase activity over the subsequent 9 months. Finally, changes in telomere length were directly related with changes in telomerase activity, and indirectly with MHI and chronic stress, as revealed by a path analysis. These results highlight the potential role of chronic stress and MHI as drivers of telomere attrition in human PBMCs, through an impairment of both energy-transformation capacity and telomerase production.
    Keywords:  Chronic stress; Mitochondrial health; Telomerase activity; Telomere attrition
    DOI:  https://doi.org/10.1038/s41598-024-77279-9
  15. J Adv Res. 2024 Dec 30. pii: S2090-1232(24)00617-9. [Epub ahead of print]
    Multi-omics approach reveals TGF-β signaling-driven senescence in periodontium stem cells.
    Bo Li, Wei Li, Yueqi Liao, Zhijie Weng, Yafei Chen, Takehito Ouchi, Yi Fan, Zhihe Zhao, Longjiang Li.
       INTRODUCTION: The periodontal ligament (PDL), a dynamic connective tissue that anchors teeth to the alveolar bone, enables tooth retention and facilitates continuous turnover. The integrity of the periodontium is maintained by periodontal ligament stem cells (PDLSCs), whose dysfunction and senescence with age can disrupt tissue homeostasis, hinder injury repair, and lead to tooth loss, ultimately impacting overall health. Transforming growth factor-β1 (TGF-β1) is known for its regenerative properties and as a functional paracrine factor in stem cell therapy, but its precise role in modulating PDLSC activity remains controversial and poorly understood.
    OBJECTIVES: This study aims to clarify the role of TGF-β1 in PDLSC senescence and identify the underlying molecular mechanisms, thereby advancing our understanding of age-related periodontal diseases and informing the development of targeted therapeutic strategies.
    METHODS: We employed spatial transcriptomics to map Tgfb1 mRNA expression in murine jawbone tissues, focusing on its distribution in the periodontium. Pseudotime analysis was performed to assess expression patterns and infer temporal dynamics. Human PDLSCs were used as a model to investigate the effects of TGF-β1 signaling, with assays conducted to examine DNA methylation, senescence phenotypes, cell cycle arrest, and underlying signaling pathways.
    RESULTS: Spatial transcriptomic profiling revealed enriched Tgfb1 expression in the periodontium, with upregulation tendencies. In human PDLSCs, TGF-β1 treatment induced a senescent phenotype marked by G2 phase cell cycle arrest and increased reactive oxygen species (ROS) accumulation. Mechanistically, TGF-β1 triggered ROS production through DNA methylation-mediated silencing of PRKAG2, a gene encoding AMPKγ2, resulting in ROS accumulation, DNA damage, and ATM signaling activation. Importantly, inhibition of ROS with N-acetyl-l-cysteine (NAC) or reversal of PRKAG2 epigenetic silencing with decitabine mitigated PDLSC senescence by suppressing ATM signaling.
    CONCLUSION: Our work presents the first spatially resolved transcriptomic landscape of murine jawbone tissues and uncovers DNA methylation as a crucial mechanism underlying TGF-β1-induced PDLSC senescence. These findings illuminate a previously unrecognized link between TGF-β1 signaling, ROS production, and epigenetic regulation, offering promising avenues for developing stem cell-based therapies to attenuate age-related periodontal diseases and improve systemic health.
    Keywords:  Cellular senescence; DNA methylation; Periodontal ligament stem cells (PDLSCs); Reactive oxygen species (ROS); Spatial transcriptomics; Transforming growth factor-β (TGF-β)
    DOI:  https://doi.org/10.1016/j.jare.2024.12.037
  16. Geroscience. 2024 Dec 30.
    A machine learning approach identifies cellular senescence on transcriptome data of human cells in vitro.
    Shamsed Mahmud, Chen Zheng, Fernando E Santiago, Lei Zhang, Paul D Robbins, Xiao Dong.
      Although cellular senescence has been recognized as a hallmark of aging, it is challenging to detect senescence cells (SnCs) due to their high level of heterogeneity at the molecular level. Machine learning (ML) is likely an ideal approach to address this challenge because of its ability to recognize complex patterns that cannot be characterized by one or a few features, from high-dimensional data. To test this, we evaluated the performance of four ML algorithms including support vector machines (SVM), random forest (RF), decision tree (DT), and Soft Independent Modelling of Class Analogy (SIMCA), in distinguishing SnCs from controls based on bulk RNA sequencing data. The dataset includes 162 in vitro samples, covering three human cell types: fibroblasts, melanocytes, and keratinocytes, and three senescence inducers: irradiation, bleomycin treatment, and replication. Under tenfold and leave-one-out cross-validation, as well as independent dataset validation, all methods provided ~ 80% or higher accuracy, with SVM reaching over 99%. Similar accuracy was achieved using expert-curated gene lists, e.g., SenMayo and CellAge, instead of our algorithm-prioritized gene list using minimum redundancy-maximum relevance (mRMR). However, only a few genes overlapped between the gene sets, suggesting a wide impact of senescence on the transcriptome. Overall, our study demonstrated a proof-of-concept for identifying senescence using ML.
    Keywords:  Cellular senescence; Machine learning; RNA sequencing
    DOI:  https://doi.org/10.1007/s11357-024-01485-6
  17. Aging Cell. 2025 Jan 03. e14463
    Tgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation to Promote SASP in Senescent Microglia.
    Zhiqiang Li, Tianxiang Wang, Sijing Du, Zelong Miao, Yujiao Zhao, Yuxiang Tang, Xianbin Meng, Shangcheng Yu, Dongyuan Zhang, Hao Jiang, Kunlin Du, Wei Wei, Haiteng Deng.
      Microglia, as resident immune cells in the central nervous system (CNS), play a crucial role in maintaining homeostasis and phagocytosing metabolic waste in the brain. Senescent microglia exhibit decreased phagocytic capacity and increased neuroinflammation through senescence-associated secretory phenotype (SASP). This process contributes to the development of various neurodegenerative diseases, including Alzheimer's disease (AD). In this study, we found that SASP was elevated in senescent microglia, and proteomics showed that Tgm2 was upregulated. Mechanistically, we revealed that Tgm2-catalyzed covalent cross-linking of IκBα at K22 and Q248 residues in the cytoplasm of microglia, resulting in the reduction of IκBα and nuclear translocation of NF-κB to promote SASP production. Treatment of senescent microglia with Tgm2 inhibitors (Tg2-IN1 and Cys-D) resulted in reduced NF-κB nuclear translocation and decreased SASP. Additionally, oral administration of Cys-D significantly improved the aging phenotype in aged mice. To summarize, Tgm2 is a potential target for antiaging, and inhibitors of Tgm2 can serve as novel prophylactics or senomorphics.
    Keywords:  IκBα; NF‐κB; SASP; Tgm2; cross‐linking; senescent microglia; senomorphics
    DOI:  https://doi.org/10.1111/acel.14463
  18. Br J Community Nurs. 2025 Jan 02. 30(1): 36-39
    The A-Z of age-related dermatological diseases.
    Mark Greener.
      Skin ageing is an inevitable process influenced by both intrinsic and extrinsic factors. Intrinsic aging leads to thinner, drier and less elastic skin with fine wrinkles, while extrinsic factors such as sun exposure, smoking and environmental stresses amplify these changes. Photo-ageing, in particular, causes deep wrinkles, uneven pigmentation and increases the risk of skin cancers. Age-related alterations in skin structure and function include thinning of the epidermis, reduced collagen and elastin and changes in fat distribution, all of which compromise the skin's barrier and mechanical properties. These changes not only increase the susceptibility to conditions such as xerosis, fungal infections and atopic dermatitis but also carry psychological implications. Interestingly, atopic dermatitis, often associated with childhood, has a secondary peak in older adults and may be linked to neurodegenerative conditions such as Alzheimer's disease. This article explores the interplay between skin aging, dermatological diseases, and their broader physical and emotional impacts.
    Keywords:  Alzheimer's disease; atopic dermatitis; dermatological diseases; fungal infections; skin ageing; toenail onychomycosis
    DOI:  https://doi.org/10.12968/bjcn.2024.0162
  19. Aging Dis. 2024 Dec 24.
    Revisiting the Benefits of Exercise for Alzheimer's Disease through the Lens of Ferroptosis: A New Perspective.
    Zikang Hao, Xinmeng Guo, Jiawen Wu, Guang Yang.
      Ferroptosis, an iron-dependent form of programmed cell death driven by oxidative stress, plays a crucial role in the progression of Alzheimer's disease (AD). Aging diminishes antioxidant systems that maintain iron homeostasis, particularly affecting the glutathione peroxidase (GPX) system, leading to increased ferroptosis and exacerbated neurodegeneration and neuroinflammation in AD. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a key transcription factor regulating genes involved in antioxidant defense and ferroptosis. In this review, we examine the interconnected roles of Nrf2 signaling, iron metabolism, and ferroptosis in AD, and discuss how regular physical exercise-known to enhance antioxidant capacity-might influence these processes. Despite evidence linking exercise to improved cognitive function in AD and its role in modulating oxidative stress, there is a paucity of research specifically addressing how exercise affects ferroptosis in the AD brain. To address this gap, we utilized bioinformatics techniques to identify potential pathways and mechanisms by which exercise may mitigate ferroptosis in AD through Nrf2 signaling. Analyzing gene expression profiles from the GEO database, we identified differentially expressed ferroptosis-related genes in the hippocampus following exercise intervention. Hub genes like SLC2A1, TXN, MEF2C, and KRAS were significantly upregulated, suggesting that exercise may activate a network enhancing antioxidant defenses and regulating iron metabolism via Nrf2. Our findings propose a novel mechanism whereby exercise alleviates abnormal ferroptosis in the AD brain through modulation of Nrf2 signaling. This study highlights the need for further research to validate these findings and explore exercise as a therapeutic strategy for AD by targeting ferroptosis.
    DOI:  https://doi.org/10.14336/AD.2024.1560
  20. Sci Rep. 2024 Dec 28. 14(1): 31291
    Curcumin liposomes alleviate senescence of bone marrow mesenchymal stem cells by activating mitophagy.
    Weiyao Li, Yixin Huang, Lei Fan, Dekyi Yangzom, Kun Zhang, Liuhong Shen, Suizhong Cao, Congwei Gu, Shumin Yu.
      The senescence of mesenchymal stem cells (MSCs) is closely related to aging and degenerative diseases. Curcumin exhibits antioxidant and anti-inflammatory effects and has been extensively used in anti-cancer and anti-aging applications. Studies have shown that curcumin can promote osteogenic differentiation, autophagy and proliferation of MSCs. Liposome, as a nano-carrier, provides a feasible strategy for improving the bioavailability and controlled-release profile of curcumin.This study aimed to evaluate the effects of curcumin liposomes (Cur-Lip) on the senescence of rat bone marrow mesenchymal stem cells (rBMSCs). Based on network pharmacology, we predicted the targets and mechanisms of curcumin on senescence of MSC. 23 key targets of Cur were associated with MSC senescence were screened out and mitophagy signaling was significantly enriched. Cur-Lip treatment alleviated senescence of D-galactose (D-gal)-induced rBMSCs, protected mitochondrial function, and activated mitophagy, which may be related to mitochondrial fission. Inhibition of mitophagy attenuated the protective effects of Cur-lip on mitochondrial function and senescence of rBMSCs. Our findings suggested that Cur-Lip could alleviate senescence of rBMSC and improve mitochondrial function by activating mitophagy.
    Keywords:  Curcumin liposomes; Mitophagy; Network pharmacology; Senescence; rBMSCs
    DOI:  https://doi.org/10.1038/s41598-024-82614-1
  21. Int J Biol Macromol. 2024 Dec 29. pii: S0141-8130(24)10102-X. [Epub ahead of print] 139291
    Stability and antioxidant function of Porphyra haitanensis proteins during simulated gastrointestinal digestion: Effects on stress resistance and lifespan extension in Caenorhabditis elegans.
    Xianjiang Ye, Ran Yang, Talha Riaz, Jicheng Chen.
      Porphyra haitanensis proteins (PHP) are natural proteins with various nutritional and biological values. This study was to analyze the composition, stability, and antioxidant activity of PHP before and after simulation gastrointestinal digestion (SGD). Caenorhabditis elegans was used as the model to investigate the functional activity and potential mechanisms of action of the PHP digestion products (PHPDP). The results showed that PHP contained 16 amino acids and exhibited high thermal stability (up to 80 °C), but dimerization or fragmentation occurred in environments with pH 3 and pH 11. After digestion, PHP released 212 bioactive peptides, which significantly enhanced its antioxidant activity and improved the resistance of C. elegans to heat, oxidative, and ultraviolet stress. Furthermore, PHPDP improved oxidative stress in C. elegans and extended its lifespan by increasing antioxidant enzyme activity and reducing malondialdehyde, lipofuscin, and reactive oxygen species levels. The mechanism of action of PHPDP likely involved regulating the insulin signaling pathway through daf-2/daf-16 and modulating the expression of oxidative stress regulators skn-1 and sod-3, thereby enhancing the organism's stress resistance and extending lifespan. This study demonstrated that P. haitanensis could serve as a reliable protein source in daily life and provided a reference for its development and application as a functional food ingredient.
    Keywords:  Anti-aging; Antioxidant; Caenorhabditis elegans; Gastrointestinal digestion; Porphyra haitanensis protein
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139291
  22. Aging Dis. 2024 Dec 31.
    Senescent Macrophages and the Lung Cancer Microenvironment: A New Perspective on Tumor Immune Evasion.
    Lexin Qin, Tingting Liang, Xinyu Zhu, Wentao Hu, Bo Li, Meidan Wei, Jiaxin Zhang, Jianxiang Li, Jin Wang.
      Lung cancer treatment is evolving, and the role of senescent macrophages in tumor immune evasion has become a key focus. This study explores how senescent macrophages interact with lung cancer cells, contributing to tumor progression and immune dysfunction. As aging impairs macrophage functions, including phagocytosis and metabolic signaling, it promotes chronic inflammation and cancer development. p16INK4a-positive macrophages are common in aged mice, and their clearance slows tumor growth, suggesting these cells support tumor proliferation and immune evasion. Targeting the senescence-associated secretory phenotype (SASP) and reprogramming senescent macrophages offers potential therapeutic benefits, including reversing immune aging and boosting anti-tumor immunity. However, translating these findings into clinical practice requires further molecular understanding and rigorous clinical trials.
    DOI:  https://doi.org/10.14336/AD.2024.1404
  23. Sci Adv. 2025 Jan 03. 11(1): eadk9373
    Histone mark age of human tissues and cell types.
    Lucas Paulo de Lima Camillo, Muhammad Haider Asif, Steve Horvath, Erica Larschan, Ritambhara Singh.
      Aging is a complex and multifaceted process involving many epigenetic alterations. One key area of interest in aging research is the role of histone modifications, which can dynamically regulate gene expression. Here, we conducted a pan-tissue analysis of the dynamics of seven key histone modifications during human aging. Our histone-specific age prediction models showed surprisingly accurate performance, proving resilient to experimental and artificial noise. Simulation experiments for comparison with DNA methylation age predictors revealed competitive performance. Moreover, gene set enrichment analysis uncovered several critical developmental pathways for age prediction. Different from DNA methylation age predictors, genes known to be involved in aging biology are among the most important ones for the models. Last, we developed a pan-tissue pan-histone age predictor, suggesting that age-related epigenetic information is degenerated across the epigenome. This research highlights the power of histone marks as input for creating robust age predictors and opens avenues for understanding the role of epigenetic changes during aging.
    DOI:  https://doi.org/10.1126/sciadv.adk9373
  24. Cell Death Differ. 2024 Dec 29.
    Inactivation of the SLC25A1 gene during embryogenesis induces a unique senescence program controlled by p53.
    Anna Kasprzyk-Pawelec, Mingjun Tan, Raneen Rahhal, Alec McIntosh, Harvey R Fernandez, Rami M Mosaoa, Lei Jiang, Gray W Pearson, Eric Glasgow, Jerry Vockley, Christopher Albanese, Maria Laura Avantaggiati.
      Germline inactivating mutations of the SLC25A1 gene contribute to various human disorders, including Velocardiofacial (VCFS), DiGeorge (DGS) syndromes and combined D/L-2-hydroxyglutaric aciduria (D/L-2HGA), a severe systemic disease characterized by the accumulation of 2-hydroxyglutaric acid (2HG). The mechanisms by which SLC25A1 loss leads to these syndromes remain largely unclear. Here, we describe a mouse model of SLC25A1 deficiency that mimics human VCFS/DGS and D/L-2HGA. Surprisingly, inactivation of both Slc25a1 alleles results in alterations in the development of multiple organs, and in a severe proliferation defect by activating two senescence programs, oncogene-induced senescence (OIS) and mitochondrial dysfunction-induced senescence (MiDAS), which converge upon the induction of the p53 tumor suppressor. Mechanistically, cells and tissues with dysfunctional SLC25A1 protein undergo metabolic and transcriptional rewiring leading to the accumulation of 2HG via a non-canonical pathway and to the depletion of nicotinamide adenine dinucleotide, NAD+, which trigger senescence. Replenishing the pool of NAD+ or promoting the clearance of 2HG rescues the proliferation defect of cells with dysfunctional SLC25A1 in a cooperative fashion. Further, removal of p53 activity via RNA interference restores proliferation, indicating that p53 acts as a critical barrier to the expansion of cells lacking functional SLC25A1. These findings reveal unexpected pathogenic roles of senescence and of p53 in D/L-2HGA and identify potential therapeutic strategies to correct salient molecular alterations driving this disease.
    DOI:  https://doi.org/10.1038/s41418-024-01428-w
  25. Sci Rep. 2024 Dec 30. 14(1): 32082
    The effects of high-intensity interval training on cognitive performance: a systematic review and meta-analysis.
    Kaihang Liu, Wei Zhao, Congcong Li, Ying Tian, Lijuan Wang, Jingyi Zhong, Xu Yan, Yezheng Wang, Liyan Wang, Hongbiao Wang.
      Cognitive decline is an important feature of an aging population. Despite the large body of research investigating the effects of high-intensity interval training (HIIT) on cognitive performance, reports of its effectiveness are inconsistent and it is difficult to determine what factors moderate these effects. The purpose of this study was to conduct a meta-analysis of existing randomised controlled trials investigating the effects of HIIT on various domains of cognitive performance, and to further examine the intervention cycle and age-related moderating effects. A comprehensive literature search was conducted across a range of databases, including PubMed, Embase, the Cochrane Library, Web of Science, Scopus, and EBSCO. The meta-analysis included data from 20 RCT studies. The results of the analyses demonstrated that HIIT significantly enhanced information processing (SMD = 0.33, 95% CI: 0.15-0.52, P = 0.0005), executive function (SMD = 0.38, 95% CI: 0.26 - 0.50, P < 0.00001), and memory (SMD = 0.21, 95% CI: 0.07-0.35, P = 0.004). Subgroup analyses demonstrated that HIIT enhanced information processing in individuals aged 60 and above, improved executive functioning in individuals of all ages, and enhanced memory in individuals aged 30 to 60. Acute HIIT improved executive function, less than 8 weeks of HIIT improved executive function and memory, and more than 8 weeks of HIIT improved information processing, executive function and memory. The findings of this study indicate that HIIT has a beneficial effect on cognitive performance. Chronic HIIT represents a potential non-pharmacological intervention for cognitive health. Further high-quality research is required to validate and extend these findings.
    DOI:  https://doi.org/10.1038/s41598-024-83802-9
  26. Geroscience. 2024 Dec 30.
    A brief report on biomarkers of cellular senescence associated with liver frailty and length of stay in liver transplantation.
    William C Miller, Matthew J Yousefzadeh, Jessica Fisher, Heidi Sarumi, Varvara Kirchner, Laura J Niedernhofer, Timothy Pruett.
      The proportion of older individuals needing liver transplantation is growing, resulting in an increasingly frail patient population. Frailty constitutes a constellation of cognitive and physical symptoms associated with aging and increases the risk of morbidity and mortality. Senescence is a programmed cell fate in response to stress implicated in causing frailty, age-related diseases, and aging itself. This study explores the relationship between cellular senescence, physical frailty, and liver transplantation. Adults > 18 years old who underwent ambulatory liver transplantation at our center between September 1, 2022, and November 30, 2022, were included. Frailty assessments were performed using the Liver Frailty Index™, and blood was collected prior to transplantation. Expression of p16INK4a and p21CIP1 mRNA in T cells was measured by RT-qPCR, an established proxy for senescent cell burden, and plasma levels of senescence-associated secretory phenotype proteins were measured by multiplex ELISA. Patient outcomes were collected via electronic medical record. Univariate linear regression analysis demonstrated a statistically significant relationship between baseline patient frailty and p16INK4a and p21CIP1 (r2 = 0.5092, p-value = 0.0205; r2 = 0.5339, p-value = 0.0164, respectively). A similar correlation occurred between p16INK4a and p21CIP1 expression and length of hospitalization (r2 = 0.4960, p-value = 0.0230; r2 = 0.5868, p-value = 0.0098, respectively). This study revealed a potential association between biomarkers of cellular senescence, physical frailty, and length of hospitalization. This warrants further investigation as biomarkers to stratify patients are needed and therapeutics to reduce senescent cell burden exists and could be deployed to improve transplant outcomes.
    Keywords:  Cellular senescence; Frailty; Liver transplantation
    DOI:  https://doi.org/10.1007/s11357-024-01482-9
  27. Int Immunopharmacol. 2025 Jan 01. pii: S1567-5769(24)02496-2. [Epub ahead of print]147 113974
    CREG1 attenuates intervertebral disc degeneration by alleviating nucleus pulposus cell pyroptosis via the PINK1/Parkin-related mitophagy pathway.
    Yang Zhang, Deguo Xing, Yi Liu, Shiyu Sha, Yueying Xiao, Zhonghao Liu, Qingfeng Yin, Zengxin Gao, Wenguang Liu.
      Intervertebral disc degeneration (IVDD) is a chronic degenerative disease with a complex pathophysiological mechanism. Increasing evidence suggests that the NOD-like receptor thermal protein domain associated protein 3 (NLRP3)-mediated pyroptosis of nucleus pulposus cells (NPCs) plays a crucial role in the pathological progression of IVDD. Pyroptosis is a novel form of programmed cell death characterized by the formation of plasma membrane pores by gasdermin family proteins, leading to cell swelling, membrane rupture, and the release of inflammatory cytokines, which trigger an inflammatory response. The close relationship between pyroptosis and mitophagy has been previously described in various diseases, but the crosstalk between pyroptosis and mitophagy in IVDD remains unexplored. Cellular repressor of E1A-stimulated genes 1 (CREG1) is a secreted glycoprotein involved in cell differentiation and homeostasis regulation and has been shown to promote lysosomal biogenesis and function. However, the potential role and underlying mechanisms of CREG1 in the progression of IVDD have not yet been reported. In this study, we first observed that CREG1 is downregulated following IVDD and that pyroptosis occurs. Furthermore, CREG1 knockdown inhibited NPC proliferation and exacerbated apoptosis and degeneration. Moreover, we confirmed that CREG1 knockdown induced NLRP3 activation while also leading to mitophagy inhibition and mitochondrial dysfunction in NPCs. CREG1 overexpression ameliorated LPS-induced mitophagy inhibition and mitochondrial dysfunction by promoting PINK1/Parkin-mediated mitophagy, thereby suppressing NLRP3 inflammasome activation. However, these protective effects were reversed by pretreatment with the mitophagy inhibitor cyclosporin A (CsA). In a rat model of IVDD, imaging and histological assessments revealed that CREG1 overexpression effectively alleviated the progression of IVDD. Additionally, CREG1 overexpression reduced the expression of NLRP3, caspase-1, and IL-1β while increasing the expression of collagen II, PINK1 and LC3, delaying the course of IVDD. Overall, this study highlights the importance of the interplay between CREG1-mediated regulation of mitophagy and pyroptosis in the pathogenesis of IVDD, identifying CREG1 as a promising therapeutic target for IVDD treatment.
    Keywords:  CREG1; IVDD; Mitophagy; NLRP3 inflammasome; Pyroptosis
    DOI:  https://doi.org/10.1016/j.intimp.2024.113974
  28. Exp Neurol. 2024 Dec 31. pii: S0014-4886(24)00461-8. [Epub ahead of print] 115135
    Astragaloside IV confers neuroprotection against radiation-induced neuronal senescence via the ERK pathway.
    Yanping Ding, Chenxin Jiang, Lili Chen, Xin Liu, Baoping Shao.
      Various factors and mechanisms, including radiation, initiate cellular senescence and are concurrent with the progression of various neurodegenerative diseases. Radiation-induced chromosomal aberrations and DNA integrity damage impact the processes of cellular growth, maturation, and aging. Astragaloside IV (AS-IV) has been documented to display significant neuroprotective effects on inflammation, oxidative stress, and cellular apoptosis; however, the precise neuroprotective mechanism of AS-IV against neuronal aging remains unclear. In this study, radiation-induced senescence models in C57BL/6 mice, PC12 cells, and primary neuronal cells were established. SA-β-gal histochemistry, flow cytometric analysis, immunofluorescence technique, and Western blotting analysis were employed to investigate the underlying mechanism of AS-IV in mitigating the aging of the brain cells caused by exposure to radiation. Our findings revealed that radiation exposure may activate the ERK pathway, leading to an increase in SA-β-gal-positive cells, elevated p21 levels, and the arrest of neuronal cells in the G1/S phase. However, AS-IV has been observed to mitigate the radiation-driven proliferation of senescent cells, by downregulating p-ERK and CDK2 expression and upregulating p21 and RB expression in treatment, thereby alleviating the aging and cognitive impairment caused by radiation. Additionally, evidence of U0126 treatment further supports these findings. In summary, our study showed that AS-IV could protect mice from radiation-induced cognitive impairment and reduce cellular senescence by regulating the ERK pathway.
    Keywords:  Astragaloside IV; Cellular senescence; ERK; Radiation
    DOI:  https://doi.org/10.1016/j.expneurol.2024.115135
  29. Front Neurosci. 2024 ;18 1503069
    Olfactory deficits in aging and Alzheimer's-spotlight on inhibitory interneurons.
    Kaoutar Elhabbari, Siran Sireci, Markus Rothermel, Daniela Brunert.
      Cognitive function in healthy aging and neurodegenerative diseases like Alzheimer's disease (AD) correlates to olfactory performance. Aging and disease progression both show marked olfactory deficits in humans and rodents. As a clear understanding of what causes olfactory deficits is still missing, research on this topic is paramount to diagnostics and early intervention therapy. A recent development of this research is focusing on GABAergic interneurons. Both aging and AD show a change in excitation/inhibition balance, indicating reduced inhibitory network functions. In the olfactory system, inhibition has an especially prominent role in processing information, as the olfactory bulb (OB), the first relay station of olfactory information in the brain, contains an unusually high number of inhibitory interneurons. This review summarizes the current knowledge on inhibitory interneurons at the level of the OB and the primary olfactory cortices to gain an overview of how these neurons might influence olfactory behavior. We also compare changes in interneuron composition in different olfactory brain areas between healthy aging and AD as the most common neurodegenerative disease. We find that pathophysiological changes in olfactory areas mirror findings from hippocampal and cortical regions that describe a marked cell loss for GABAergic interneurons in AD but not aging. Rather than differences in brain areas, differences in vulnerability were shown for different interneuron populations through all olfactory regions, with somatostatin-positive cells most strongly affected.
    Keywords:  Alzheimer’s disease; aging; inhibition; interneurons; olfaction
    DOI:  https://doi.org/10.3389/fnins.2024.1503069
  30. Int J Biol Macromol. 2024 Dec 29. pii: S0141-8130(24)10129-8. [Epub ahead of print] 139318
    Anti-angiogenic activity and mechanism of fucoidan from brown algae, Sargassum Naozhouense mediated by intracellular antioxidation.
    Shengtao Yang, Yi Liu, Yu Pei, Zhong-Ji Qian.
      Fucoidan has various physiological activities, and its structure is also different according to different brown algae. In this study SNF (Sargassum Naozhouense fucoidan) was extracted by acid extraction method, and its relative molecular weight was determined to be 631.40 kDa. The structure contains 42 % hydroxyl with sulfate group, and it is mainly composed of fucose, galactose and xylose. In the activity study, intracellular oxidative stress is closely related to angiogenesis. The results show that SNF could ameliorate cellular oxidative stress injury by inhibiting the production of intracellular reactive oxygen species (ROS), nitric oxide (NO) and DNA damage in HepG2/CYP2E1 cell. In addition, SNF can reduce the activity of Matrix Metallopeptidase (MMP-2/9), and inhibit hypoxia-inducible factor-1α (HIF-1α) expression by regulating the downstream PI3K/AKT and Ras/MAPK pathways, thereby preventing vascular endothelial growth factor (VEGF) production, and further inhibits VEGF receptor-2 activation and ultimately inhibits angiogenesis in HT1080 and HUVECs. Therefore, SNF has the potential to develop tumor prevention functional substances and can provide theoretical basis for the high-value comprehensive utilization of brown algae.
    Keywords:  Anti-angiogenic activity; Antioxidant; Fucoidan; Sargassum Naozhouense
    DOI:  https://doi.org/10.1016/j.ijbiomac.2024.139318
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