Aging & Longevity

Mild disruptions to mitochondrial function can lead to the activation of an adaptive program that extends animal lifespan. The mitochondrial unfolded protein response (UPRmt) is associated with such conditions that prolong lifespan. We previously discovered that methionine restriction, resulting from the genetic loss of methionine synthase in C. elegans, activated the UPRmt and extended lifespan. Here, we demonstrate that methionine restriction activates the UPRmt and delays aging within the...

Aging is a complex biological process often characterized by increased vulnerability to disease, infection, and death. This increased vulnerability is mechanistically linked to a progressive and functional decline of the immune system. In humans, aged T cells lose their ability to effectively surveil complex microenvironments, thereby decreasing their capacity to clear infections, eradicate diseases, and maintain physiological homeostasis. However, specific mechanisms by which aged T cells lose...

Circulating non-cellular factors, such as plasma proteins, contribute to various features of aging. To determine the impacts of endogenous circulating factors on human age-related bioenergetic decline, we treated primary human fibroblasts with serum samples representing the adult life-course. Our results demonstrate that the maximal mitochondrial bioenergetic capacity of fibroblasts treated with serum is negatively correlated with the chronological and epigenetic age of the serum donor. Using...

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Social and economic conditions shape healthy aging, but it remains unclear whether policies that modify these conditions change aging-related biomarkers or later-life functional trajectories. The growing availability of biomarker data in longitudinal cohorts, together with the wider use of experimental and quasi-experimental designs in social policy research, creates new opportunities to evaluate how social conditions become biologically embedded. We argue that policy experiments can strengthen...

Social gradients in health and aging are well documented in human societies: individuals who experience low social status, loneliness or early-life adversities show accelerated biological aging, an increased burden of chronic diseases and a lower survival rate. However, how these exposures become biologically embedded remains incompletely understood, and causal inference remains limited. Here, we discuss emerging natural and experimental animal models of the social determinants of aging, which...

Social determinants of health, the conditions in which people are born, grow, live, work and age, shape brain aging and dementia. Yet evidence is dominated by Global North populations and often relies on single indicators (for example, education or income), limiting risk characterization and generalizability across settings. This Perspective provides a global, integrative overview of multidimensional, multilevel and life-course approaches to social determinants of health and exposome research in...

Across global contexts, proportions of older people living in rural places are increasing. Given that place of residence and rurality have both been identified as potential determinants of health inequity, it is important to understand how, and in what circumstances, rural living affects healthy aging. This foundational review examines the academic literature to identify and critique specific rural social determinants that drive health inequities for older people and to examine how these have...

Population aging has widened the gap between life expectancy and healthspan. Yet aging trajectories remain strikingly heterogeneous even among populations facing comparable harmful environmental exposures, including air pollution, extreme temperatures, toxic metals, unsafe water and sanitation, noise and poor housing. Why similar environmental risks produce divergent patterns of multimorbidity, disability and functional decline is a central research question. This Review proposes environmental...

There is accumulating evidence that social isolation has a serious impact on the health and well-being of older adults, with this concern endorsed by the US Surgeon General, the World Health Organization Commission on Social Connection report, and other national and international policy forums. Social isolation can be viewed as part of the broader agenda of the social determinants of healthy aging. Evidence from higher-income countries on the relationship of isolation with poor health outcomes...

Healthy aging is shaped by the exposome-the accumulation of exposures experienced across the life course arising from intersections of the natural, physical, social, community and policy environments in which people age. This Consensus Statement reports recommendations from the Gateway Exposome Coordinating Center to accelerate life-course research on the exposome's impacts on healthy aging, including Alzheimer's disease and related dementias. Recommendations centered on five themes are...

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Aging induces structural and functional alterations in the skin, characterized by diminished collagen synthesis and impaired cellular turnover, resulting in progressive thinning and reduced elasticity. The incorporation of plant-derived extracts into skincare formulations has gained increasing attention due to their richness in polyphenols with potent anti-aging properties. Adansonia digitata (baobab, AD) is a bioactive rich African tree, yet its implications in skin aging have been...

CONCLUSIONS: In low-incidence areas, individuals with a prior TB history show significantly elevated IGRA positivity. The link between TBI and abnormal chest imaging suggests a practical role for radiography in screening. The inverse association of fasting blood glucose (FBG) with IGRA positivity introduces a new immunologic insight for aging populations that requires further exploration. Collectively, these findings deliver actionable local evidence to inform targeted screening strategies for...

CONCLUSIONS: The application of the FTD-FRS in a population of community-dwelling older adults considered healthy and functionally independent demonstrated variability in functional performance across several domains of everyday functioning. Within the context of this exploratory study, the FTD-FRS proved to be a useful and accessible instrument for the descriptive characterization of functional performance. Future studies incorporating complementary cognitive, neuropsychological, and...

CONCLUSIONS: IC decline is heterogeneous. The Discordant Capacity group had lower fall risk, possibly due to cognitive preservation or reduced exposure, warranting cautious interpretation. These findings support shifting from "one-size-fits-all" to precision, profile-based ICOPE implementation to optimize functional ageing in rapidly ageing populations.

CONCLUSIONS: The experiences of decline in intrinsic capacity and associated intervention needs among disabled older adults in nursing homes appear to exhibit distinct hierarchical characteristics consistent with the social-ecological systems theory within this single-center context. Key challenges include inadequate cognitive awareness of intrinsic capacity, low health empowerment, constrained health-promoting behaviors, and a lack of systematic support systems. These findings provide...

Aging is the major risk factor for neurodegenerative disease, yet how it affects different cells in the primate brain remains unclear. In this issue of Cell, Yang et al. present a single-nucleus atlas of the aging macaque brain that, together with recent work by Zhang et al., reveals context-dependent aging programs, sex-biased transcriptional aging, and molecular links to Alzheimer's disease.

The human striatum governs diverse motor, cognitive, and affective behaviors yet lacks the obvious cytoarchitectural boundaries defining functional territories elsewhere in the brain. Using Slide-tags single-nucleus spatial transcriptomics, we profiled 1.1 million cells across 19 postmortem donors to uncover the striatum's spatial organization. These data revealed a consistent subdivision of the striatum into six zones, each defined by molecularly distinct populations of spiny projection neurons...