Aging & Longevity

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...

No abstract

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...

The cellular and molecular bases of inter-individual variation in the human brain are not yet understood, particularly beyond the neocortex. Here, we describe cellular and gene-expression variation in the striatum and prefrontal cortex from single-nucleus RNA sequencing (snRNA-seq) analysis of 3.9 million nuclei from 178 adult brain donors. People with more astrocytes, microglia, or oligodendrocyte precursor cells (OPCs) in any one brain region tended to have this property in all gray-matter...

Brain aging is a complex process with profound health and societal consequences. However, the molecular and cellular pathways that govern its progression, and inter- and intra-individual variation, remain poorly defined. We present a transcriptomic atlas of 5.3 million cells from 582 samples spanning 11 brain regions of 55 rhesus macaques (aged 0.5-21 years). We identify age-depleted and vulnerable neuronal populations and subtle, age-associated compositional differences in glia-detectable only...

Single-cell reference mapping is increasingly central to translating heterogeneous datasets into consistent representations of cell identity. As cell-type atlases expand in scale and complexity, mapping new data to shared references enables reproducible annotation, cross-study integration, and accumulation of biological knowledge. We present MapMyCells, an open-source, high-performance framework for mapping diverse single-cell omics datasets to hierarchical reference taxonomies with minimal...

High-quality neurotypical postmortem human brain tissue is essential for constructing comprehensive human brain cell atlases, but it is difficult to obtain. Here, we describe the establishment of UC Irvine's Brain Procurement Program, a coordinated multi-institutional pipeline to collect and process neurotypical donor brains for multiomic mapping studies within the National Institute of Health (NIH) BRAIN Initiative Cell Atlas Network (BICAN) consortium. Through partnerships with the Orange...

Aging is characterized by progressive tissue and organ decline, with chronic low-grade inflammation (inflammaging) implicated as a central driver. Granzyme K (GzmK), a serine protease that is markedly upregulated in aged memory CD8^(+) T cells, is proposed to be a central mediator of both immune and organismal aging. Using young and aged GzmK^(-/-) mice, we showed that GzmK was dispensable for the major hallmarks of immune aging, including T cell dysfunction, but was a critical driver of...

Low-grade inflammation is persistent with advancing age in healthy people and mice. Endothelial cells and large arteries increasingly express pro-inflammatory cytokines, coinciding with increased T cell infiltration into the aorta. Arterial stiffness is an independent risk factor for cardiovascular diseases, and stiffness increases with age. T cells particularly affect vascular dysfunction, and we have shown that T cell depletion in old mice prevented elevations in stiffness. We sought to...

INTRODUCTION: Declines in function occur in both "normal" aging (in the absence of disease) and age-related pathological contexts, like Alzheimer's disease (AD). Whether "anti-aging" interventions (that extend lifespan) also promote cognitive function in aging and AD remains largely unexplored.