bims-caglex Biomed News
on Cellular aging and life extension
Issue of 2025–02–02
eight papers selected by
Mario Alexander Guerra Patiño, Universidad Antonio Nariño
  1. Stochasticity in dietary restriction-mediated lifespan outcomes in Drosophila.
  2. Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance.
  3. Alternative Splicing: Emerging Roles in Anti-Aging Strategies.
  4. Transforming exercise evidence into societal action for healthy longevity.
  5. Senotherapy: Implications for Transplantation.
  6. Natural anti-aging strategies: mechanisms and role of phytoextracts in combating skin aging.
  7. Norharmane prevents muscle aging via activation of SKN-1/NRF2 stress response pathways.
  8. A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.
  1. Geroscience. 2025 Jan 31.
    Stochasticity in dietary restriction-mediated lifespan outcomes in Drosophila.
    Olivia L Mosley, Joel A Villa, Advaitha Kamalakkannan, Eliyashaib James, Jessica M Hoffman, Yang Lyu.
      Dietary restriction (DR) is widely considered to be one of the most potent approaches to extend healthy lifespan across various species, yet it has become increasingly apparent that DR-mediated longevity is influenced by biological and non-biological factors. We propose that current priorities in the field should include understanding the relative contributions of these factors to elucidate the mechanisms underlying the beneficial effects of DR. Our work conducted in two laboratories represents an attempt to unify DR protocols in Drosophila and to investigate the stochastic effects of DR. Across 64 pairs of survival data (DR/ad libitum, or AL), we find that DR does not universally extend lifespan. Specifically, we observed that DR conferred a significant lifespan extension in only 26.7% (17/64) of pairs. Our pooled data show that the overall lifespan difference between DR and AL groups is statistically significant, but the median lifespan increase under DR (7.1%) is small. The effects of DR were overshadowed by stochastic factors and genotype. Future research efforts directed toward gaining a comprehensive understanding of DR-dependent mechanisms should focus on unraveling the interactions between genetic and environmental factors. This is essential for developing personalized healthspan-extending interventions and optimizing dietary recommendations for individual genetic profiles.
    Keywords:   Drosophila ; Dietary restriction; Health; Longevity; Stochasticity; Variation
    DOI:  https://doi.org/10.1007/s11357-025-01537-5
  2. Adv Sci (Weinh). 2025 Jan 31. e2416823
    Activation of Nuclear Receptor CAR: A Pathway to Delay Aging through Enhanced Capacity for Xenobiotic Resistance.
    Jing Yu, Xiaoyan Gao, Hang Shi, Lijun Zhang, Wenlong Nie, Ruochen Zhang, Minglv Fang, Ying Liu, Yingxuan Yan, Bingbing Fan, Chengyuan Wu, Cheng Huang, Shengjie Fan.
      Environmental factors are linked to aging and age-related diseases. Emerging evidence suggests that enhancing body's resistance to xenobiotics might be an anti-aging strategy. The constitutive androstane receptor (CAR) regulates drug-metabolizing enzymes and transporters, coordinating metabolism and immune responses to adapt to stress triggered by exogenous exposure. However, the impact of activating CAR on aging remains unknown. In this study, Caenorhabditis elegans (C. elegans), drug-induced premature aging mice, and senescence accelerated P8 (SAMP8) mice are used as models to explore the effects of CAR activation on lifespan and healthspan, along with the underlying mechanisms. The results showed that hCAR agonist CITCO and mCAR agonist TCPOBOP prolonged the lifespan and healthspan in model organism. The longevity effects of CITCO and TCPOBOP were attenuated in CAR homozygous nhr-8/daf-12 mutant C. elegans as well as CAR-/- mice. In C. elegans, CITCO activated both anti-stress and detoxification genes, and increased the resistance to environmental adversities. Additionally, the lifespan-extending and xenobiotic resistant effects of CITCO might be related to the regulation of age-related pathways. Furthermore, CITCO improved age-related neurodegeneration in C. elegans models. Taken together, the results suggest that the longevity effects of CAR agonists may be related to the enhancement of xenobiotic resistance of animals.
    Keywords:  age‐related neurodegeneration; anti‐aging; constitutive androstane receptor (CAR); environmental stimulus; xenobiotic resistance
    DOI:  https://doi.org/10.1002/advs.202416823
  3. Biomolecules. 2025 Jan 15. pii: 131. [Epub ahead of print]15(1):
    Alternative Splicing: Emerging Roles in Anti-Aging Strategies.
    Lingyue Gao, Rong Jia.
      Alternative splicing plays a fundamental role in gene expression and protein complexity. Aberrant splicing impairs cell homeostasis and is closely associated with aging and cellular senescence. Significant changes to alternative splicing, including dysregulated splicing events and the abnormal expression of splicing factors, have been detected during the aging process or in age-related disorders. Here, we highlight the possibility of suppressing aging and cellular senescence by controlling alternative splicing. In this review, we will summarize the latest research progress on alternative splicing in aging and cellular senescence, discuss the roles and regulatory mechanisms of alternative splicing during aging, and then excavate existing and potential approaches to anti-aging by controlling alternative splicing. Novel therapeutic breakthroughs concerning aging and senescence entail a further understanding of regulating alternative splicing mechanically and accurately.
    Keywords:  aging; alternative splicing; anti-aging; splicing factor
    DOI:  https://doi.org/10.3390/biom15010131
  4. Arch Gerontol Geriatr. 2025 Jan 20. pii: S0167-4943(25)00026-3. [Epub ahead of print] 105768
    Transforming exercise evidence into societal action for healthy longevity.
    Liang-Kung Chen.
      
    Keywords:  Exercise prescription; Healthy aging; Healthy longevity; Physical activity; Precision health
    DOI:  https://doi.org/10.1016/j.archger.2025.105768
  5. Transplantation. 2025 Jan 31.
    Senotherapy: Implications for Transplantation.
    Martin Jaros, Anette Melk.
      Cellular senescence has been identified as a potential driver of age-associated loss of organ function and as a mediator of age-related disease. Novel strategies in targeting senescent cells have shown promise in several organ systems to counteract functional decline, chronic inflammation, and age-dependent loss of repair capacity. Transgenic models have provided proof of principle that senolysis, the elimination of senescent cells, is an attractive strategy to overcome many age-related pathologies. The translation into clinical application is now possible with the emergence of drug-based senotherapies. In this review, we will discuss different senotherapeutic approaches and their modes of action. Senolytics eliminate senescent cells preferentially through the induction of apoptosis in senescent but not in normal cells, whereas senomorphics rather interact with the proinflammatory profile present in senescent cells. In the context of transplantation, the natural clearance of senescent cells might be reduced because of dysfunctional immune surveillance under immunosuppression. The transplantation setting allows for different applications of senotherapies. Conditioning donor organs before and during the ex situ phase offers the opportunity to interfere with accumulating senescence, ultimately reducing the burden of life-limiting comorbidities in chronically ill recipients.
    DOI:  https://doi.org/10.1097/TP.0000000000005291
  6. Arch Dermatol Res. 2025 Jan 28. 317(1): 312
    Natural anti-aging strategies: mechanisms and role of phytoextracts in combating skin aging.
    Vishakha Saini, Geeta Deswal, Ajmer Singh Grewal, Anjali Sharma, Kumar Guarve.
      
    Keywords:  Antioxidants; Bioactive compounds; Collagen synthesis; Natural anti-aging; Phytoextracts; Skin aging
    DOI:  https://doi.org/10.1007/s00403-025-03807-w
  7. Redox Biol. 2025 Jan 27. pii: S2213-2317(25)00025-4. [Epub ahead of print]80 103512
    Norharmane prevents muscle aging via activation of SKN-1/NRF2 stress response pathways.
    Farida S Nirmala, Hyunjung Lee, Yejin Cho, Min Young Um, Hyo Deok Seo, Chang Hwa Jung, Jeong-Hoon Hahm, Jiyun Ahn.
      Sarcopenia, the age-related decline in muscle mass and function, is a significant contributor to increased frailty and mortality in the elderly. Currently, no FDA-approved treatment exists for sarcopenia. Here, we identified norharmane (NR), a β-carboline alkaloid, as a potential therapeutic agent for mitigating muscle aging. We aimed to determine the ability of NR to delay muscle aging in Caenorhabditis elegans (C. elegans), mouse, and muscle cells in mice and humans. NR treatment improved swimming ability and increased the maximum velocity in aged C. elegans. Transcriptomic analysis revealed that NR upregulated detoxification genes in C. elegans, including cytochrome P450, UGT, and GST enzymes. NR-induced benefits were dependent on the SKN-1/Nrf2 stress response pathway. In mammalian models, NR delayed cellular senescence in human skeletal muscle myoblasts and enhanced myogenesis in C2C12 cells and primary aged myoblasts. NR supplementation in aged mice prevented muscle loss, improved muscle function, and reduced markers of cellular senescence. We found that the p38 MAPK pathway mediated NR activation of Nrf2 by disrupting the Nrf2-Keap1 interaction. NR also improved oxygen consumption rates and promoted mitochondrial biogenesis. These findings suggest that NR is a promising candidate for preventing sarcopenia and improving muscle health.
    Keywords:  Mitochondrial function; Myogenesis; Norharmane; Nrf2; SKN-1; Sarcopenia
    DOI:  https://doi.org/10.1016/j.redox.2025.103512
  8. Cancers (Basel). 2025 Jan 14. pii: 257. [Epub ahead of print]17(2):
    A Review of Telomere Attrition in Cancer and Aging: Current Molecular Insights and Future Therapeutic Approaches.
    Mina Iskandar, Miguel Xiao Barbero, Muhamed Jaber, Roy Chen, Romulo Gomez-Guevara, Edwin Cruz, Sandy Westerheide.
       BACKGROUND/OBJECTIVES: As cells divide, telomeres shorten through a phenomenon known as telomere attrition, which leads to unavoidable senescence of cells. Unprotected DNA exponentially increases the odds of mutations, which can evolve into premature aging disorders and tumorigenesis. There has been growing academic and clinical interest in exploring this duality and developing optimal therapeutic strategies to combat telomere attrition in aging and cellular immortality in cancer. The purpose of this review is to provide an updated overview of telomere biology and therapeutic tactics to address aging and cancer.
    METHODS: We used the Rayyan platform to review the PubMed database and examined the ClinicalTrial.gov registry to gain insight into clinical trials and their results.
    RESULTS: Cancer cells activate telomerase or utilize alternative lengthening of telomeres to escape telomere shortening, leading to near immortality. Contrarily, normal cells experience telomeric erosion, contributing to premature aging disorders, such as Werner syndrome and Hutchinson-Gilford Progeria, and (2) aging-related diseases, such as neurodegenerative and cardiovascular diseases.
    CONCLUSIONS: The literature presents several promising therapeutic approaches to potentially balance telomere maintenance in aging and shortening in cancer. This review highlights gaps in knowledge and points to the potential of these optimal interventions in preclinical and clinical studies to inform future research in cancer and aging.
    Keywords:  age-related diseases; aging; alternative lengthening of telomere; biomarkers; cancer; premature aging disorders; telomerase reactivation; telomere attrition; therapeutics
    DOI:  https://doi.org/10.3390/cancers17020257
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