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Background Cellular senescence, a permanent state of replicative arrest in otherwise proliferating cells, is a hallmark of aging and has been linked to aging-related diseases. Many genes play a role in cellular senescence, yet a comprehensive understanding of its pathways is still lacking. Results We develop CellAge ( http://genomics.senescence.info/cells ), a manually curated database of 279 human genes driving cellular senescence, and perform various integrative analyses. Genes inducing cellular senescence tend to be overexpressed with age in human tissues and are significantly overrepresented in anti-longevity and tumor-suppressor genes, while genes inhibiting cellular senescence overlap with pro-longevity and oncogenes. Furthermore, cellular senescence genes are strongly conserved in mammals but not in invertebrates. We also build cellular senescence protein-protein interaction and co-expression networks. Clusters in the networks are enriched for cell cycle and immunological processes. Network topological parameters also reveal novel potential cellular senescence regulators. Using siRNAs, we observe that all 26 candidates tested induce at least one marker of senescence with 13 genes ( C9orf40 , CDC25A , CDCA4 , CKAP2 , GTF3C4 , HAUS4 , IMMT , MCM7 , MTHFD2 , MYBL2 , NEK2 , NIPA2 , and TCEB3 ) decreasing cell number, activating p16/p21, and undergoing morphological changes that resemble cellular senescence. Conclusions Overall, our work provides a benchmark resource for researchers to study cellular senescence, and our systems biology analyses reveal new insights and gene regulators of cellular senescence.

Age-related conditions are the leading causes of death and health-care costs. Reducing the rate of aging would have enormous medical and financial benefits. Myriad genes and pathways are known to regulate aging in model organisms, fostering a new crop of anti-aging companies. Approaches range from drug discovery efforts to big-data methods and direct-to-consumer (DTC) strategies. Challenges and pitfalls of commercialization include reliance on findings from short-lived model organisms, poor biological understanding of aging, and hurdles in performing clinical trials for aging. A large number of potential aging-associated interventions and targets exist, but given the long validation times only a small fraction can be explored for clinical applications. If even one company succeeds, however, the impact will be huge. It is increasingly being recognized that directly targeting the aging process, as opposed to individual aging-related diseases or symptoms, is a viable strategy. This is leading to R&D with the ultimate aim of commercializing therapies directed at slowing aging itself. Some therapeutic approaches – direct-to-consumer nutraceuticals and trial-tested scientific diets – do not require FDA approval, which can significantly reduce their time to market. To slow the aging process, nonstandard therapies such as blood-based therapies are also being tried. Big-data approaches are being harnessed in an attempt to build models of healthy aging. Approaches are increasingly coming directly from aging results in model organisms.

A list of this decade's most prominent names in ageing research would undoubtedly include many women who have led the field in recent years. While the field, and science in general, still have far to go in achieving gender parity in opportunities and recognition, we can celebrate the progress made to date. However, the longer ‘history of the field’ that many of us present in our classrooms, conference halls and writings often tends to be dominated by men. Although numerous men have made fundamental observations that have shaped our understanding of ageing from both a mechanistic and evolutionary perspective, the unfortunate reality is that women making similar contributions have not received equal recognition throughout much of our field's history. As a starting point for wider representation and further conversations in this area, we present here a short list of women—Marjory Warren, Lillian Jane Martin, Margaret Alexander Ohlson, Rebeca Gerschman and Marion J. Lamb—whose contributions were foundational to ageing research in the 20th century. Their work spanned theoretical, experimental and clinical insight into the biology of ageing—and yet their names are too seldom mentioned when introducing our field. We hope this list can be a starting point for a more inclusive recognition of the diverse scientists who helped pave the way for our field today. Pioneering women in ageing research. Photo credits: Marjory Warren, Photo: Archives of the British Geriatrics Society; Lillien Martin, courtesy of the Department of Special Collections, Stanford University Libraries, SC1071, Stanford Historical Photograph Collection, Box 17; Margaret Ohlson, image reproduced with permission from The Journal of the Academy of Nutrition and Dietetics (Wenberg & Lechowich, 1997); Rebeca Gerschman, photo free of access from https://sebbm.es/mujer‐y‐ciencia/rebeca‐gerschman/; Marion Lamb, from https://alchetron.com/Marion‐J‐Lamb.

As healthspan and lifespan research breakthroughs have become more commonplace, the need for valid, practical markers of biological age is becoming increasingly paramount. The accessibility and affordability of biological age predictors that can reveal information about mortality and morbidity risk, as well as remaining years of life, has profound clinical and research implications. In this review, we examine 5 groups of aging biomarkers capable of providing accurate biological age estimations. The unique capabilities of these biomarkers have far reaching implications for the testing of both pharmaceutical and non-pharmaceutical interventions designed to slow or reverse biological aging. Additionally, the enhanced validity and availability of these tools may have increasingly relevant clinical value. The authors of this review explore those implications, with an emphasis on lifestyle modification research, and provide an overview of the current evidence regarding 5 biological age predictor categories: Telomere length, composite biomarkers, DNA methylation “epigenetic clocks,” transcriptional predictors of biological age, and functional age predictors.

The widespread use of the name ‘geroscience’ in the science of aging is sometimes met with a wary attitude by biogerontologists other than its inventors. Here, we provide an overview of its origin and evolution to assess what exactly it is and to discuss its theoretical and biological relationship to earlier movements of anti-aging medicine and biogerontology more generally. Geroscience posits that targeting aging may offer a cost-effective approach to improve late-life health in humans, and because aging is malleable in model organisms and what regulates this is sufficiently understood, the time is ripe for moving forward to translational and clinical research. The geroscience agenda has rebranded imagery of past traditions, yet the claim that therapies for human aging are ready or within the imminent future is contestable and on brand with tradition, even if biogerontology has made great progress in the past decades.

Background Grip strength is a key functional marker of musculoskeletal aging, widely used to assess sarcopenia. In preclinical research, multiple measurement methods are often combined to enhance reliability, but standardization remains challenging. To improve measurement robustness, we previously developed a composite strength score (SS5) that integrates five different grip strength tests into a single variable. While SS5 provides a comprehensive evaluation, its implementation is time‐consuming, limiting feasibility in large‐scale studies. In this study, we also examine two simplified composite scores, SS2 and SS3, as potential streamlined alternatives. Additionally, although normalizing grip strength to body weight is widely used, its appropriateness in geriatric mouse models has never been formally validated. Methods Forelimb grip strength was assessed in a cohort of 160‐aged C57BL/6J mice using five methods: Weight Lift Tests (Deacon protocol with sponge weights and a modified version with metal wire weights), the Cage Lift Test and the Grip Strength Meter (trapeze bar and grid). Additionally, a cross‐sectional group of 173 mice was analysed to assess the correlation between grip strength and muscle size. Each method was evaluated for its correlation with age, ability to detect sex differences, variability and association with muscle size. Results All methods strongly correlated with age (−0.518 ≤ rs ≤ −0.306). The Grip Strength Meter (trapeze bar) and modified Deacon method were the most effective in detecting sex differences (p < 0.001). While all methods correlated with muscle size (0.153 ≤ rs ≤ 0.332), the modified Deacon method and Grip Strength Meter showed the strongest associations. The mean coefficient of variation (CV%) ranged from 7% to 17%, demonstrating good repeatability. Notably, despite being widely used, normalization of grip strength to body weight was found to introduce bias in geriatric mice, as age‐related weight loss distorts strength assessments. Absolute values proved to be a more reliable measure. To improve efficiency while maintaining reliability, we developed two new composite scores (SS2 and SS3) by integrating a subset of methods from SS5. These scores preserved the strong correlation with age observed in SS5 while reducing the number of required tests, enhancing feasibility. Conclusions Combining multiple grip strength assessments improves measurement reliability in aging studies. The newly proposed SS2 and SS3 scores provide a streamlined yet robust alternative to SS5, improving standardization and facilitating future comparisons in preclinical sarcopenia research. Our findings also challenge the routine normalization of grip strength to body weight in geriatric mice, emphasizing the importance of using absolute values to avoid bias.

Human ageing is a complex biological process characterized by age-related functional decline, resulting in increased vulnerability to illness, disease and death. Although advances in molecular gerontology have elucidated the cellular and molecular underpinnings of ageing, translating these insights into effective strategies that extend both health span and lifespan in humans remains a pressing challenge. A persistent obstacle is the absence of a coherent and operational definition of health within the field. Traditional models define health as the absence of disease or functional impairment, but this conception becomes increasingly inadequate in the context of ageing, where multimorbidity, subclinical dysfunction and frailty often occur without overt pathology. Ageing can be conceptualized as a contraction of the homeodynamic space, reflecting diminished resilience, adaptability and repair capacity. From a philosophical perspective, health may be understood as a sustained pattern of adaptive traits over time. In this review, we explore conceptual distinctions between health, illness, disease and related terms, with particular attention to clinically significant yet non-pathological states. We argue that biogerontology should adopt resilience-based and systems-level frameworks to capture the complexity of ageing and to guide the development of interventions that support functioning and quality of life across the lifespan. We also propose an integrative model that links personalized geroscience approaches with lifespan-related, behavioural and social factors to promote healthy ageing.

If a shortened lifespan is evolutionarily advantageous, it becomes more likely that nature will strive to change it accordingly, affecting how we understand aging. Premature mortality because of aging would seem detrimental to the individual, but under what circumstances can it be of value? Based on a relative incremental increase in fitness, simulations were performed to reveal the benefit of death. This modification allows for continuous evolution in the model and establishes an optimal lifespan even under challenging conditions. As a result, shorter-lived individuals achieve faster adaptation through more frequent generational turnover, displacing longer-lived ones and likely providing a competitive advantage between species. Contrary to previous assumptions, this work proposes a mechanism by which early death, e.g., due to aging, may contribute to evolution.

Verification of signaling molecules in the saliva is a non-invasive method of diagnosis and evaluation of treatment effectiveness in different pathologies. Sirtuins (SIRT), proteins from NAD-dependent histone deacetylases, are supposed to be involved in the pathogenesis of Alzheimerэs disease. Age-related decrease in sirtuins expression induces many pathophysiological processes that could lead to neurodegeneration. We studied the expression of SIRT1, SIRT3, SIRT5, and SIRT6 in the hippocampus and saliva of humans without neurological pathologies and in patients with Alzheimer’s disease of elderly and senile age. In elderly and senile patients, the expression of SIRT1, SIRT3, and SIRT6 in the hippocampus and saliva was 1.5-4.9-fold reduced in comparison with healthy individuals of the corresponding age. In healthy senile persons, the expression of SIRT6 in the hippocampus and saliva was 2.5-4.5-fold lower than in healthy elderly individuals. Measurement of SIRT1, SIRT3, and SIRT6 concentration in the saliva can be used as an additional method for intravital non-invasive diagnosis of Alzheimer’s disease in patients of advanced age. SIRT6 concentration in the saliva can be recommended as a marker for assessment of the rate of aging.

The 50th Anniversary of the National Cancer Act of 1971 is the opportune time to critically reflect on the determinates of what the philosopher of science Philip Kitcher calls “responsible biology”. Responsible biology entails that scientists have an obligation to reflect on the ends, and not just the means, of scientific research and to conceive of themselves as artisans working for the public good. Taking stock of the successes and limits of the half a century “war on cancer” reveals the importance of attending to the most significant risk factor for cancer and other chronic diseases- aging itself. The case is made for considering the biology of aging, and the aspiration to slow the rate of biological aging, as critical components of responsible biology in an aging world. As growing numbers of humans survive into late life, the primacy the goal of disease elimination occupies within biomedical research must be revised, and greater effort should be directed towards the goal of increasing the human healthspan and delaying and compressing disease, frailty and disability in late life.