Aging & Longevity

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.

CONCLUSION: U3A students had higher healthy aging and quality of life scores than their peers who were not enrolled in the program, and these differences remained significant after adjustment for sociodemographic and health-related variables. A moderate positive correlation was also found between healthy aging and quality of life. These findings indicate that U3A programs may be considered within the scope of community-based healthy aging initiatives. However, causal inferences cannot be made...

Healthy older adults exhibit both selective impairments in episodic memory - memory for events situated within a specific time and place - and deficits in executive function, reflected by difficulty switching between different tasks and inhibiting task-irrelevant information. Prior work has shown that older adults show diminished mnemonic brain state engagement - recruitment of whole brain activity patterns that selectively support memory encoding and memory retrieval. Our hypothesis is that...

Cellular senescence is a state of irreversible cell-cycle arrest that prevents cancer but promotes aging and inflammation. Conflicting molecular profiles of senescence may arise from contamination by neighboring proliferating cells. Here, we developed SenLect (senescence selection), a genetically encoded system for purifying senescent cells in culture. SenLect expresses mCherry-2A-PuroR under the senescence-activated miR-146a promoter, providing senescent cells a selective advantage over...

Alzheimer's disease (AD), the leading cause of dementia, is increasingly recognized as a metabolic disorder characterized by disrupted insulin and insulin-like growth factor-1 signaling in the brain, a concept now referred to as type 3 diabetes. Central to this perspective is the insulin receptor substrate-1/phosphoinositide 3-kinase/protein kinase B/mechanistic target of rapamycin (IRS-1/PI3K/Akt/mTOR) cascade, which acts as the primary convergence point linking systemic insulin resistance to...

Replicative senescence links telomere shortening to irreversible proliferative arrest and is widely recognized as a major tumor-suppressive mechanism. At the organismal level, however, progressive accumulation of senescent cells contributes to tissue dysfunction, chronic inflammation, and aging. Accumulating evidence suggests that telomere shortening influences telomeric and subtelomeric chromatin organization and transcription through mechanisms that remain incompletely understood. Building...

Frailty is a multisystem clinical syndrome closely linked to cognitive aging, yet its relationship with brain pathology and contribution to neurological outcomes remain unclear. We examined neuroimaging correlates of frailty and evaluated their integrative impact on incident dementia within a cerebral frailty risk score (CFRS) framework. In a population-based UK Biobank cohort, we analyzed neuroimaging-derived phenotypes, including cerebral volumetrics and thickness, white matter...