Aging & Longevity

Extraembryonic tissues and many cancers share unusual DNA methylation landscapes, but how these states arise remains unclear. Here, we use GATA6- and CDX2-driven reprogramming of mouse embryonic stem cells to track genome-wide epigenetic remodeling during acquisition of extraembryonic cell fates. Despite activating distinct transcriptional programs from non-overlapping genomic targets, both transcription factors trigger rapid and genomically synchronized convergence to cancer-like DNA...

Aging is a multifactorial process shaped by genetic, metabolic, and environmental factors. Yet one physical constant-gravity-has rarely been considered as a potential contributor to the aging process. This perspective explores the hypothesis that chronic exposure to Earth's gravity, through its lifelong hydrostatic effects on cerebral blood flow (CBF), may represent an unrecognized driver of systemic aging. The brain, particularly deep regulatory centers in the hypothalamus and brainstem,...

Cardiac aging is traditionally framed as a progressive loss of energetic capacity, yet accumulating evidence indicates that iron-dependent lipid peroxidation and ferroptotic susceptibility may contribute to age-related myocardial vulnerability. Here, we integrate evidence linking mitochondrial quality control, membrane lipid remodeling, antioxidant capacity, and iron handling to the emergence of a ferroptosis-permissive state in aging cardiomyocytes. We further propose that aerobic exercise may...

The ability to recover skeletal muscle after periods of disuse declines with age leading to persistent deficits in strength and function that extend beyond muscle mass loss. Here, we investigated whether age-related alterations in lipid remodeling contribute to impairment in skeletal muscle recovery following disuse. Lipidomic and oxylipin profiling revealed that aged mouse muscle is characterized by sustained phosphatidylcholine and omega-6-dependent COX-prostaglandin signaling during early...

Natural products derived from traditional medicines are valuable sources of potential geroprotective compounds; however, their translation into therapeutic candidates is limited by chemical complexity, polypharmacology, limited mechanistic resolution, and lengthy experimental validation. Artificial intelligence (AI) offers an emerging framework for integrating chemical, pharmacological, multi-omics, imaging, and literature derived data to accelerate natural product anti-aging research. This...

Continuum elastic shells with residual stresses can exhibit complex motions that require vanishing elastic energy to excite, also called geometric zero modes, enabling them to be driven by weak and generic energy inputs. Despite recent interest in these modes, we understand very little about their dynamical properties. Plates with a curved, rather than flat, in-plane geometry, also called non-Euclidean plates, are one example in which residual stresses and geometry combine to produce a continuum...

Meningiomas exhibit substantial molecular, anatomical, and microenvironmental heterogeneity, yet the spatial organization of their lipid biology remains poorly understood. Emerging lipidomic studies demonstrate extensive remodeling of membrane, signaling, and mitochondrial lipid classes, with profiles varying according to molecular genotype, histopathological grade, and potentially patient characteristics. In parallel, developmental, single-cell, and spatial studies have revealed the meninges...

BackgroundUnderstanding changes in long-term care (LTC) applicants' needs informs service planning.ObjectiveTo examine trends in functional impairment and multimorbidity among Hong Kong's publicly funded LTC applicants during 2001-2019.MethodsWe analyzed interRAI assessments from 315,556 applicants aged ≥60. Hierarchical mixed-effects models estimated trends in physical and cognitive impairment, loneliness, and multimorbidity, adjusting for age, birth cohort, and sociodemographic factors....

ObjectiveHispanic individuals are understudied in cognitive aging research and are disproportionately exposed to crime, yet the cognitive consequences of this exposure remain unclear. We examined whether county-level crime moderates the association between physical functioning (PF) and cognitive change among Mexican Americans aged 75 years and older without cognitive impairment at baseline.MethodsParticipants included 1,189 older adults from the Hispanic Established Populations for the...

Aging research has advanced along two largely parallel paths. Experimental biology has transformed aging research by establishing that aging is biologically malleable and identifying conserved molecular and cellular mechanisms that regulate lifespan and healthspan. In parallel, population research has revealed substantial heterogeneity in human aging and identified social, environmental, behavioral, and genetic factors associated with differences in aging trajectories. Despite a shared goal of...

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...