Aging & Longevity
MKP-2 Genetic Depletion Modulates Adipose Lipid Composition, Cellular Senescence, and Aging in Mice
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...
Brain structure-function decoupling and neuromuscular coordination during gait and sit-to-stand in healthy aging
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.
Tree Shrew as an Emerging Model for Aging Research: Characterization of Senescence and Therapeutic Interventions
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...
Sex- and age-specific risk factors for possible sarcopenic obesity in community-dwelling older adults: a cross-sectional study
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.
Lower-limb blood flow restriction training for improving multiple dimensions of muscle strength and physical performance in older adults: a systematic review and meta-analysis
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.
Redox-dependent remodeling of mitochondrial nucleoids contributes to bioenergetic decline during neuronal aging
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...
Hypothalamus-driven brain health through metabolic flexibility
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...
Older Adult Experiences with Food and Nutrition in the United States: A Qualitative Systematic Review
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...
Evidence for Spermine Oxidase (SMOX) as a Regulator of Skeletal Muscle Mass Throughout the Lifespan
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...
Rethinking inflammaging: spatiotemporal decoupling and the failure of inflammatory regulation
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...
Sex-specific trajectories in the association between serum uric acid and biological age acceleration: A cross-sectional study
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....
Exploring the Role of Transposable Elements to Sex Gap in Longevity in Three Drosophila Species
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...
Multidimensional MRI Reveals Cellular-Scale Microstructural Phenotypes in Human Brain Aging
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...
Sex-specific associations between handgrip strength and all-cause mortality in older Mexican adults
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....
Epigenetic aging during the COVID-19 pandemic: A prospective longitudinal study with prepandemic baseline data in children, adolescents, and adults
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...
Hypothalamic lncRNA <em>Synage</em> prevents age-related sperm quality decline by suppressing A-type potassium currents in GnRH neurons
Age-related decline in male fertility, including diminished sperm quality, poses significant risks to offspring health and is exacerbated by modern trends toward delayed parenthood. Focusing on the hypothalamus-pituitary-testis axis, which governs hormonal control of male reproduction, we identified Synage, a long noncoding RNA expressed in the hypothalamic medial preoptic area (mPOA). We found that Synage expression in gonadotropin-releasing hormone (GnRH) neurons decreases with age,...
Unpacking transatlantic income inequality
This paper uses newly harmonized survey and register data on incomes and labor market outcomes as the basis for consistent comparisons of inequalities across 17 North American and European countries over the period 1995-2021. We examine trends in disposable income inequality in the working-age population, defined as persons aged 25 to 60, as well as its component parts of market income inequality and redistribution through government tax and transfer systems. We adjust incomes to allow for...
Senescent CD8 T effector memory cells are functionally impaired, enriched in aging and disease, and a barrier to immunotherapy
Senescent cells play important roles in various biological processes that promote fitness and health; however, their timely elimination by immune cells is critical to maintain tissue homeostasis and prevent disease. Despite this, senescent cells accumulate systemically with age, suggesting that certain immune cells also become senescent and dysfunctional during aging. In support of this, we previously demonstrated that CD8 T cells, immune cells capable of targeting senescent cells, increasingly...
Nicotine attenuates D-galactose- induced hippocampal aging-like alterations with alpha7-nAChR- associated mechanisms
CONCLUSION: Nicotine attenuated selected D-galactose-associated behavioral and hippocampal alterations. The genotype comparisons support α7-nAChR-associated modulation of platform-site crossings, serum GSH, and hippocampal IBA1. They do not establish that changes in brain GSH or amyloid production mediate these effects, or that all nicotine responses share one receptor-dependent mechanism.
Resistance Training and Respiratory and Immune-Related Outcomes in Older Adults: A Randomized Controlled Trial
Age-related declines in pulmonary function and immune regulation increase morbidity and mortality in older adults. Physical activity mitigates these effects, but the isolated impact of resistance training (RT) on lung function and immune responses remains unclear. Sixty-nine older adults without participation for at least one year in structured exercise programs (aged 60-85 years) were recruited from a community extension program at a Brazilian university and randomized into an RT group (n = 31)...
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