Aging & Longevity

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...

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.

How does one map, measure, and model the aging brain?

Parkinson's disease (PD) is a neurodegenerative disorder for which advancing age is the major risk factor. Aging and PD share several features, including chronic neuroinflammation and pathological protein accumulation. This overlap suggests that mechanisms driving the aging process may also contribute to the onset and progression of PD. In this narrative review, we examine mitochondrial dysfunction as a shared feature of aging and PD, focusing on energy production, calcium buffering, apoptosis,...

ObjectivesNeighborhood resources are protective factors for healthy cognitive aging, yet the impact of these resources may vary by urbanicity. We examined urban-rural differences in the association between the availability of neighborhood social services, religious, and civic organizations, and cognitive decline among older Mexican Americans.MethodData from 628 participants (M(Age) = 80) in 2004-2013 Hispanic Established Populations for the Epidemiologic Study of the Elderly were linked to the...