Aging & Longevity

Aging selectively degrades neuronal structure and function, yet the signals that actively preserve neuronal integrity over adult life remain incompletely defined. In Caenorhabditis elegans, the PVD sensory neuron develops progressive excessive higher-order dendritic branching during normal aging that correlates with declines in proprioceptive locomotion. Using this system as a quantitative in vivo readout of neuronal healthspan, we identify the cholecystokinin-like neuropeptide NLP-12 as a...

DNA double-strand breaks (DSBs) are the most genotoxic form of DNA damage. Unrepaired DSBs may cause loss of chromosome fragments at mitosis, while incorrectly repaired DSBs can cause chromosome aberrations and other adverse effects, leading to cell cycle arrest, senescence, cell death, or neoplastic transformation. Detecting and quantifying DSBs is important in studies of genome instability, aging, and cancer. Methods of detecting and quantifying DSBs fall into two broad categories:...

Bone marrow (BM) adiposity changes radically through the lifespan, but this phenomenon is poorly characterized and understood in humans. Large datasets of magnetic resonance imaging (MRI) scans of the head have been collected to study the human brain, but also contain unexploited information about other organs. We developed an artificial neural network that localizes calvarial BM in T1-weighted MRI head scans, enabling us to study its composition in several large MRI datasets, and to model...

PHB2 (prohibitin 2), a well-known inner mitochondrial membrane mitophagy receptor, has recently emerged as a potential sensor of intracellular bacteria. A recent study shows that increased exposure of the inner mitochondrial membrane protein PHB2 enables its interaction with bacterial surface proteins and the recruitment of the E3 ubiquitin ligases ARIH1 (ariadne RBR E3 ubiquitin protein ligase 1) or PRKN (parkin RBR E3 ubiquitin protein ligase), thereby promoting xenophagy. This finding expands...

BackgroundParental longevity is linked to better offspring cognition, with limited evidence from middle-income countries. We examined associations between parental longevity and cognition in Mexico while controlling for health, socioeconomic status (SES), and genetic factors.MethodsWe used the 2018 wave of the Mexican Health and Aging Study (n = 5,049; age 65+). Maternal/paternal longevity was based on survival to age 85 or older. We used latent variable regressions to estimate associations with...

Aging is characterized by a gradual decline in physiological functions, impaired cellular repair mechanisms, and increased disease susceptibility. Mitogen-activated protein kinase phosphatase-2 (MKP-2) regulates diverse biological functions, including regulation of infection, brain activity, nutrient metabolism, and cell-cycle progression, but its role in senescence and adipose lipid metabolism in vivo remains unclear. Here, we investigated the effects of MKP-2 deficiency on cellular senescence...

CONCLUSION: Healthy aging is associated with task-dependent reorganization of lower-limb neuromuscular control and selective basal ganglia-striatal structure-function alterations. These findings provide multimodal evidence of parallel central and peripheral reorganization during healthy aging and identify candidate brain-muscle associations for future longitudinal and confirmatory investigation.

Aging is characterized by progressive physiological decline and increased susceptibility to age-related diseases. Conventional rodent models have contributed significantly to our understanding of aging, yet their translational relevance is limited by substantial evolutionary divergence from humans. Here, we introduce the tree shrew (Tupaia belangeri chinensis) as a novel and biologically relevant model organism for aging research. In vitro, we induced cellular senescence in tree shrew...

CONCLUSIONS: Risk factors for PSO differ substantially by sex and age. These findings support targeted prevention strategies: weight control in men, nutritional and inflammatory monitoring in women, metabolic management in younger-old adults, and weight control in the oldest-old.

CONCLUSION: Both LL-BFR and W-BFR may improve lower-limb muscle strength and physical performance in older adults, particularly when compared with no intervention or conventional walking. Lower-limb BFR training may therefore have a potential role in sarcopenia prevention and early management in aging populations, especially for individuals who are unable to tolerate high mechanical loads.

Why mitochondria progressively fail in aging neurons remains a fundamental question in neurobiology. Although bioenergetic decline and oxidative stress are hallmarks of aging, whether redox signaling remodels mitochondrial nucleoids (mt-nucleoids) to impair neuronal bioenergetics remains unclear. Using aged mouse neurons and human induced pluripotent stem cell (iPSC)-derived neurons, we demonstrate that redox-driven mt-nucleoid remodeling underlies reduced mtDNA transcript abundance and...

Organismal physiology depends on continuous, non-hierarchical communication among cells, tissues, and organs. We argue that this communication rests on metabolic flexibility-the capacity of cells and tissues to adapt substrate use to changing energetic demands-and that the hypothalamus serves as the central hub coordinating this flexibility across the body. Using hypothalamic agouti-related protein (AgRP) and pro-opiomelanocortin (POMC) neurons as a model, we show these melanocortin neurons do...

This systematic review aimed to synthesize and critically appraise qualitative evidence on U.S. older adults' experiences with food and nutrition. Searches of five databases identified 40 qualitative studies published between 2000 and 2023. Studies were included if they examined food- and nutrition-related experiences among U.S. adults aged 60 and older using qualitative interview or focus group methods. A thematic synthesis approach was used to summarize key findings across studies, and the...

Age-associated loss of muscle mass and function, termed sarcopenia, increases morbidity and mortality risks concomitant with decreased physical activity. Chronic exercise training is the most effective countermeasure against sarcopenia, but physical limitations create a barrier to participation in the elderly. Investigation into alternative pharmaceutical and nutraceutical treatments to prevent sarcopenia and maintain muscle plasticity late-in-life are therefore warranted. Polyamine metabolism...

Chronic low-grade inflammation (inflammaging) is a central feature of aging, yet its magnitude and trajectory vary substantially among individuals and tissues. This variability is not fully explained by chronological age or cumulative inflammatory exposure. We therefore examine inflammaging through a spatiotemporal framework focused on how inflammatory responses are initiated, contained, resolved, and distributed across tissues. The framework integrates established mechanisms-including defective...

This study aimed to elucidate the independent, sex-specific dose-response trajectories between serum uric acid (SUA) and phenotypic age acceleration (PhenoAgeAccel), while carefully accounting for concurrent metabolic confounding. Using multivariable linear regression and sex-stratified restricted cubic splines (RCS) in a large-scale cross-sectional cohort, we found that elevated SUA showed a robust inverse association with biological aging in both sexes upon comprehensive metabolic adjustment....

In Drosophila, like other animal species, females tend to live longer than males, a phenomenon known as sex gap in longevity (SGL). One possible explanation could involve the activity of transposable elements (TE). TEs are normally repressed by epigenetic mechanisms, but this regulation weakens with age. Y chromosomes are enriched in TEs, and age-related TE activity may therefore be more pronounced in older males, likely affecting longevity (toxic Y hypothesis). Using three Drosophila species...

Brain aging is accompanied by profound cellular and microstructural changes that precede overt tissue loss, yet in vivo MRI studies largely emphasize macroscopic measures or isolated diffusion and relaxation metrics, providing limited insight into how cellular-scale tissue architecture is altered across the adult lifespan. Here, we apply multidimensional diffusion-relaxation MRI (MD-MRI) to map voxel-wise microstructural phenotypes in cognitively unimpaired adults spanning early adulthood to...

Handgrip strength (HGS) declines with age and is associated with morbidity and mortality. This study aimed to investigate sex-specific associations between absolute and allometric HGS and all-cause mortality in Mexican adults aged 50 years and older. We analyzed data from the Mexican Health and Aging Study, including 1917 adults aged ≥ 50 years with HGS assessed at wave 3. Absolute HGS (kg) and allometric HGS (HGS/height²) were examined using sex-specific quartiles and standardized z-scores....

Psychosocial stress is a risk factor for aging-related diseases. The COVID-19 pandemic placed a psychosocial burden on individuals, potentially increasing the risk for aging-related diseases for which epigenetic clocks are used as early biomarkers. Based on four epigenetic clocks (DunedinPACE, GrimAge2, Horvath, and PedBE), we investigated whether epigenetic aging changed during the pandemic and whether these changes were associated with objective and subjective pandemic-related stressors and...