Aging & Longevity

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...

With an aging donor population, ischemic and inflammatory injury during organ procurement and preservation may be associated with senescence-associated programs influencing graft biology. Although donor type-specific injury patterns are known, their role in driving cellular senescence and downstream inflammatory responses remains unclear. We performed smart-3SEQ bulk RNA-sequencing on human liver tissue obtained from donation after brain death (DBD) and donation after circulatory death (DCD)...

Synaptome architecture describes the spatiotemporal distribution of highly diverse excitatory synapses throughout the brain. Whether and how this architecture is impacted by experience and sensory input is unknown. We found that environmental enrichment and monocular visual deprivation drive large-scale reconfiguration of excitatory synapse populations in more than one hundred regions of the mouse brain. Different experiences modify distinct subsets of synapse types and subtypes, with patterns...

Somatic evolution in ageing tissues underlies many cancers^(1,2). However, our quantitative understanding of the rules governing this pre-cancerous evolution remains incomplete. Here we exploit a unique collection of serial blood samples³, collected annually for up to a decade and beginning as early as 15 years before diagnosis of acute myeloid leukaemia, to provide a quantitative description of pre-cancerous evolutionary dynamics. Using deep duplex sequencing and evolutionary theory, we...

Aging is associated with a progressive decline in immune surveillance, yet the mechanisms that constrain this process remain incompletely understood. Here we uncover a lipid-biomechanical mechanism in human natural killer (NK) cells that contributes to age-related immune decline. We show that aging drives a coordinated metabolic and physical state in NK cells, marked by lipid accumulation, increased membrane fluidity, reduced cortical stiffness and defective immune synapse organization,...

Metabolic ageing and associated changes in lipid mobilisation have been heavily studied in humans and model taxa, yet remain poorly understood in farmed animals, with potentially important implications for health and welfare outcomes. Here, we compared three stages of aquaculture production in Atlantic salmon (Salmo salar), the world's most commercially valuable farmed fish. Our sampling captures smoltification, a key life-cycle transition, followed by the metabolic changes occurring during...

CONCLUSION: No substantive difference existed in healthy aging levels between rural-urban older adults, while the associations of individual attributes and social support with healthy aging varied across rural-urban groups. Therefore, differentiated social support systems tailored to local conditions should be established for rural and urban areas to continuously advance equitable healthy aging.