Aging & Longevity

The tumor suppressor p53 orchestrates critical cellular responses to stress, including cell cycle arrest, DNA repair, senescence, and apoptosis. While extensive research has elucidated many aspects of p53 function, the isoform-specific mechanisms governing cell fate decisions remain incompletely understood. Here, we leverage the simplified p53 gene architecture in Drosophila to systematically dissect the apoptotic and tumorigenic potential of individual p53 isoforms, uncovering fundamental...

Operating nanometal catalysts under harsh reaction conditions often leads to their disintegration into less active single atoms or clusters, which is considered as a primary cause of catalyst deactivation and loss of active components. In the current work, our theoretical calculations on CeO₂-supported Rh catalysts first reveal that pre-filling surface vacancies with suitable single metal atoms renders the subsequent anchoring of Rh atoms on supports energetically unfavorable. Guided by this...

Controlled signaling activity is vital for normal tissue homeostasis and oncogenic signaling activation facilitates tumorigenesis. Here, we combine single-cell transcriptomics with in-depth genetic and imaging analysis to investigate the role of the EGFR-Ras and Hedgehog signaling pathways in homeostasis of the Drosophila follicle stem cell lineage. We find that Hedgehog signaling simultaneously promotes an undifferentiated state and induces differentiation via activation of the...

Advances in transcriptomic technologies have progressively transformed the questions we can ask and answer about muscle stem cells (MuSCs) during aging. Early microarray and bulk RNA sequencing studies established foundational population-level signatures of aged MuSCs, including attenuation of myogenic and metabolic programs as well as induction of inflammatory and stress-associated transcription. However, these averaged readouts obscured cell-to-cell variability and rare functional states. The...

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CONCLUSIONS: Most older Americans are concerned about access to long-term care and costs, yet remain divided on who primarily should pay for caregiving costs. Caregivers are both more concerned about long-term care access and more likely to support the government's primary responsibility for caregiving costs than noncaregivers. Policymakers should consider more options for access to affordable, high-quality long-term care, and financial supports for caregivers.

CONCLUSION: Immunosenescence plays a crucial role in IS pathogenesis and recovery, with chronic inflammation and immune dysfunction exacerbating stroke outcomes in older adults. Targeting immune markers, particularly IL-6 and the Th17/Treg imbalance, may offer new therapeutic approaches to improve stroke prognosis in aging populations. Further research is needed to develop interventions that address immunosenescence in IS.

INTRODUCTION: Sleep quality is often thought to be a key determinant of cognitive performance, particularly in older adults who experience age-related changes in sleep architecture. However, the extent to which nightly variations in sleep quality impact next-day cognitive performance remains unclear-in part because it has only recently become practical to measure sleep over multiple nights.

Accurate age estimation is key to understanding life history, population ecology, and effective management of valuable commercial and ecologically relevant species. While DNA methylation-based epigenetic clocks are well developed in mammals, their application in fish is limited. In contrast to mammals, fish lack identified universal fish epigenetic markers. Here we explore the potential of ultra-conserved elements (UCEs) as age predictor markers in albacore tuna (Thunnus alalunga), a worldwide...

In a little over 100 years, global life expectancy has increased by ∼60%. Paradoxically, it has been estimated that we now exercise five times less than we did 100 years ago. Despite a marked increase in life expectancy, the prevalence of non-contagious diseases (NCDs), otherwise known as "chronic lifestyle diseases," such as cardiovascular disease, type 2 diabetes, cognitive diseases, and cancer, has increased. Here, we discuss the concept of "exercise as medicine" for the treatment of NCD and...

DNA damage and mutations in hematopoietic stem cells (HSCs) enable clonal hematopoiesis (CH). Such damage occurs across a lifetime, but its origins remain unknown. Here, we demonstrate that endogenous formaldehyde causes HSC attrition and subsequently CH. We generated conditional mouse models lacking formaldehyde detoxification and Fanconi anemia (FA) DNA repair in blood. Formaldehyde protection was crucial for embryonic HSC emergence and throughout life. Despite severe deficiencies in HSCs,...

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Cataract is a leading cause of visual impairment worldwide, and its prevalence is increasing with population aging. The majority are age-related cataracts (ARC), clinically classified into nuclear, cortical, and posterior subcapsular cataracts (PSC) by opacity location. Mechanisms of cataractogenesis remain incompletely understood. While cortical and nuclear cataracts are largely attributed to crystallin aggregation, such protein-centric mechanisms fail to explain the early onset and axial...

CONCLUSION: Neighbourhoods play a crucial role in supporting older adults' flourishing, but evidence on causal pathways and life-course dynamics remains limited. The proposed integrative framework enhances conceptual clarity and provides a foundation for longitudinal research to guide place-based interventions for positive ageing.

With age, human skin undergoes a progressive decline in essential functions, including barrier protection, immunity, and wound healing capacity, which underlie many age-related skin diseases. Skin aging is not only driven by chronological aging, but also strongly influenced by extrinsic stressors, notably ultraviolet radiation, pollutants, and diet. Thus, understanding the complex interplay between these intrinsic and extrinsic factors is essential for developing strategies to preserve skin...

Frailty is an established benchmark of aging-related decline, yet most measures of frailty focus on physical decline. Increasing evidence that social environments influence trajectories of aging has led to growing interest in social frailty. Recently, a 10-item Social Frailty Index (SFI-10) was developed using data from the Health and Retirement Study (HRS) that used 8 social items plus chronological age and sex to predict mortality. This study evaluates the validity of the SFI-10, providing...

Interorgan communication is essential for metabolic homeostasis and healthy aging, with adipose tissue acting as a central hub that coordinates systemic metabolism, stress responses, and longevity. Here, we show that the miRNA-processing enzyme Dicer-1 (Dcr-1) acts in the fat body (FB) to regulate Dilp2 secretion from brain insulin-producing cells (IPCs), thereby modulating systemic insulin signaling and lifespan in Drosophila. Dcr-1 expression is reduced in multiple long-lived conditions, and...

Aging is a major contributor to the escalating prevalence of heart failure (HF). Ferroptosis has been implicated in age-related disorders and cardiovascular diseases. The role of ferroptosis in age-related HF remains unclear. Here, we show that aged rats exhibit impaired cardiac function accompanied by hallmark features of ferroptosis, including reduced glutathione peroxidase 4 (GPX4) expression and excessive lipid peroxidation. Consistently, cardiomyocyte-specific GPX4 knockout mice develop...

Cancer is associated with biological aging and functional decline; however, few studies have simultaneously examined objective changes in physical function and biological aging in older adults who develop cancer. We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health...

Frailty is a modifiable aging-related condition driven by chronic inflammation and metabolic dysregulation, which are influenced by diet. Metabolomic profiling captures individual metabolic responses and can uncover mechanisms linking diet to frailty. This study examined the effects of food-derived metabolites on changes in frailty risk, both directly and through inflammatory pathways. This longitudinal study included baseline and three-year follow-up data from 9992 participants aged 45-85 years...