Aging & Longevity

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...

Beyond total volume, how physical activity is distributed, timed, and structured across the 24-h cycle may reflect aspects of brain aging missed by conventional measures. We examined how these activity dimensions relate to cognitive status, cognitive performance, and Alzheimer's disease (AD)-related plasma biomarkers. In this cross-sectional analysis of 164 adults aged 50-89 from the Human Connectome Project-Connectomics in Brain Aging and Dementia study, 7-day wrist actigraphy measured activity...

Evidence linking socioeconomic mobility to depressive symptoms in older adults in low- and middle-income countries is limited. We examined childhood-to-adulthood socioeconomic position (SEP) mobility in India. The primary cross-sectional analysis used complete-case data from 30,358 adults aged ≥ 60 years in the Longitudinal Ageing Study in India Wave 1. Childhood SEP was recalled; adulthood SEP reflected per capita consumption expenditure. Mobility was classified as consistently high, upward,...

Super-carbon-chain compounds (SCCCs), marine long-carbon-chain polyketides featuring numerous carbon stereocenters, fall into untapped chemical space in between drug-like small molecules and biopolymers. Due to mass-material unavailability and flexible-structure complexity, the reliable stereochemical assignment of SCCCs has long remained stagnant. In this work, a modern microalgal biomass production-platform is created for pilot-scale cultivation of marine dinoflagellates to produce over 100...

Alzheimer's disease (AD), a neurological disorder characterized by progressive deterioration of cognitive function, has complex pathogenic mechanisms and lacks curative therapies with proven efficacy. Aging and inflammatory responses, which play indispensable roles in the onset and progression of AD, are closely intertwined with mitochondrial dysfunction. During aging, a series of degenerative alterations, including accumulated mitochondrial DNA (mtDNA) mutations, excessive mitochondrial...

Mitochondrial dysfunction and declining ATP production are common features of aging, yet whether ATP availability itself directly regulates cellular lifespan is unclear. However, the causal relationship between cellular ATP homeostasis and aging has not been established. Here, we developed a synthetic system to manipulate intracellular ATP independently of endogenous energy production by expressing a plasma membrane-targeted nucleotide transporter, NTT1, from the intracellular parasite...

ObjectivesWhile studies have linked nature exposure to better cognitive health, little is known about the specific types or amounts needed for health benefits. Many studies regarding the health benefits of nature lack racially and ethnically diverse aging populations and have small sample sizes, limiting their generalizability. This study investigated the relationship between land cover types and cognitive function in older Mexican American adults from Wave 5 (2004-2005) of the Hispanic...

The hepatic microenvironment undergoes dynamic remodelling in advanced liver fibrosis. Hyaluronic acid (HA), a key component of this fibrotic microenvironment, plays a key role in disease progression. While cellular senescence is one of the fates that activated HSCs undergo and is associated with fibrosis resolution, the relationship between HA and HSC senescence in advanced liver fibrosis remains unclear. This study aimed to elucidate the specific mechanisms by which HA regulates HSC...

Nickel (Ni), the last essential trace element identified in plants, has long been enigmatic regarding the genetic basis underlying its homeostasis and its agricultural significance. Using genome-wide association analysis, we identified ZmNAET1 as a key transporter controlling Ni allocation to seeds. Mechanistically, ZmNAET1 mediates nicotianamine secretion and enables nicotianamine-dependent phloem loading of Ni in nodes and subsequent Ni translocation into sink organs. Mutants lacking ZmNAET1...