Aging & Longevity
AGGF1 delays endothelial cellular senescence through the TGFB3-TAK1-AMPK signaling axis
Endothelial senescence is a critical contributor to vascular aging and age-related vasculopathies. Our previous work identified AGGF1 as a regulator of cell cycle progression and anti-inflammatory signaling. However, whether AGGF1 modulates endothelial senescence remains unclear. Here, we demonstrate that AGGF1 is downregulated in both replicative and DOX-induced senescent HUVECs. AGGF1 knockdown accelerated cellular senescence as evidenced by senescence markers, including increased SA-β-gal...
Late-night dinner, skipping breakfast, and the risk of dementia in Japan: the LIFE Study
Evidence on meal timing and dementia is limited. We examined late-night dinner and skipping breakfast in relation to incident dementia. We conducted a population-based cohort study using linked medical insurance claims, long-term care insurance claims, and government-subsidized health checkup data from 19 participating in the Longevity Improvement & Fair Evidence (LIFE) Study. Cohort entry was from April 2016 to March 2021. Late-night dinner (dinner within 2 h of bedtime ≥ 3 times/week) and...
Media Behaviors Considered by Older Adults During Health Emergencies: A Cross-National Study
PurposeTo identify the predictors of the technology-assisted behaviors older adults would consider implementing once encountered with a health concern and seeking help. To understand this phenomenon, the study tapped into the technology familiarity approach and the media richness theory.MethodsData were obtained from the 2020 wave of the Ageing, Communication, Technologies (ACT) survey and analyzed using logistic regression models. The sample included 3,926 internet users 63-97 years old from...
Inflammaging and neurovascular unit dysfunction in cognitive ageing: mechanisms, biomarkers, and therapeutic opportunities
Age-related cognitive decline is increasingly recognised as arising from interacting immune and neurovascular vulnerabilities rather than from isolated insults. In this Review, we synthesise current human and mechanistic evidence within a convergence framework in which inflammaging and neurovascular unit (NVU) dysfunction are conceptualised as a feedback-coupled system. Persistent immune remodelling may promote endothelial activation, redox imbalance, pericyte-astrocyte support failure,...
The Effects of Multi-Session Resistance Exercise on Cognitive Function in Healthy Adults: A Systematic Research Review and Meta-Analysis
CONCLUSIONS: The findings indicate that the cognitive effects of multi-session resistance exercise are domain-specific rather than uniform across cognitive abilities. Resistance exercise appears particularly promising for supporting cognitive processes involving executive control, working memory, and rapid information processing. However, interpretation should remain cautious given heterogeneity across studies, limited evidence in some domains, and variation in intervention duration, intensity,...
Serum 25(OH) vitamin D and SIRT1- VDR- miR-124 expression: A controlled interventional study in a vitamin D-deficient male rat model
CONCLUSION: A putative epigenetic relation was found between miR-124 levels and their association with SIRT1. The investigated biomarkers of aging are associated with serum concentration of 25(OH) vitamin D in a middle-aged vitamin D-deficient rat model, which supports the need for mechanistic investigation in future studies.
Systemic and local chronic inflammation and hormone disposition promote a tumor-permissive environment for breast cancer in older women
Estrogen receptor-positive (ER^(+)) breast cancer is the most common subtype of breast cancer and is an age-related disease. How systemic and tumor microenvironment hormone signaling intersects with chronic inflammation and how this shapes aging-associated tumor biology remain incompletely understood. Here, using an aged rat model of ER^(+) tumors, we identify age-associated differences in tumor development and immune features. In parallel, analysis of samples from patients with ER^(+)/HER2^(-)...
Inflammation-linked aging signals in frozen single-cell foundation models: donor-aware detection and robustness testing
Single-cell foundation models such as scGPT and Geneformer are large neural networks trained on human single-cell RNA-seq data. They were never shown chronological age during training. Do their internal representations nevertheless encode aging biology in a way that can be interpreted, and how should we test whether an apparent aging signal is real biology rather than an artifact of which donors and cell types happened to be sampled?. We applied a nine-step evaluation pipeline to two foundation...
Why Do Older Adults Disengage From Routine Medical Care? Psychological Distress, Wealth Stratification, and Health System Disengagement in Later Life
ObjectiveMany older adults stop seeing a doctor despite having insurance and significant health needs. This study asks whether psychological distress predicts disengagement from care, beyond structural barriers.MethodUsing three waves of the Health and Retirement Study (N = 5,184 adults 65+), we model whether distress in one wave predicts no medical contact in the next, testing whether wealth weakens this link.ResultsOlder adults with more psychological distress were significantly more likely to...
Transport of endo-β-mannosidase AtEBM from the cytoplasm to the vacuole through the autophagy pathway in <em>Arabidopsis</em>
Macroautophagy/autophagy is a conserved eukaryotic intracellular degradation pathway, with specialized forms such as the biosynthetic cytoplasm-to-vacuole targeting (Cvt) pathway in yeast, which selectively delivers several resident hydrolase precursors to the vacuole rather than for turnover. Although the core autophagy machinery is highly conserved between yeast and plants, whether autophagy plays a biosynthetic role in transporting vacuolar hydrolases in plants has remained unclear. Here, we...
B Lymphocytes in the Adipose Tissue Microenvironment: Multifaceted Roles in Inflammation and Metabolic Dysfunction
Adipose tissue (AT) is now recognised as a dynamic immunometabolic organ in which coordinated interactions between adipocytes, stromal cells, vascular elements, and resident immune populations are essential for maintaining metabolic homeostasis and endocrine function. Beyond its classical role in energy storage, AT actively regulates local and systemic immune responses through the production of adipokines, cytokines, chemokines, and lipid mediators. Among adipose-resident immune cells, B...
Metabolic Signatures of Aging and Gametogenesis in Hydra oligactis
Aging can be experimentally induced in Hydra oligactis, making it an exception among the "immortal" cnidarian genus Hydra. In response to cold temperatures, H. oligactis polyps switch from asexual to "emergency" sexual reproduction and eventually age and die. We used GC-MS-based metabolite profiling to characterize cold-induced (CI) metabolic reprogramming during concurrent sexual differentiation and aging in H. oligactis. Metabolites in four clusters either decreased or increased progressively...
IDEAL-Age: an interpretable deep learning framework for single-cell resolution profiling of immunological aging
Immunosenescence increases susceptibility to infection and reduces vaccine responsiveness, yet bulk transcriptomic clocks obscure the cellular heterogeneity underlying this process. Here, we present IDEAL-Age, an interpretable deep learning framework that operates directly on single-cell PBMC transcriptomes. Benchmarking against 35 methods across independent cohorts demonstrates superior predictive performance. The framework's interpretability uncovers linear and non-linear gene contribution...
p38 MAPK and MDT-15 mediate SKN-1-dependent metformin-induced protection against mitis group streptococci in Caenorhabditis elegans
Mitis group streptococci are opportunistic pathogens residing in the oral cavity, where they produce hydrogen peroxide (H(2)O(2)), a key virulence factor contributing to their pathogenesis. We previously demonstrated that these bacteria kill the nematode Caenorhabditis elegans through H(2)O(2) production. Metformin, a widely used biguanide drug for managing blood glucose levels, has shown promising effects on aging by extending lifespan in worms and mice, and has also demonstrated potential...
LINE-1 CpG methylation in canine blood and cortical DNA tracks epigenetic changes with age
Aging is accompanied by progressive epigenetic alterations, including changes in DNA methylation affecting both gene-associated regions and repetitive elements such as LINE-1 retrotransposons. Reduced epigenetic repression of transposable elements has been implicated in age-related genomic instability. Circulating cell-free DNA (cfDNA) provides a minimally invasive substrate for monitoring systemic molecular changes; however, age-related LINE-1 methylation dynamics in cfDNA remain poorly...
Unveiling the AcSirt2-FOXO-Mitophagy Axis: Insights Into Mitochondrial Quality Control and Delayed Aging in Apis cerana
Cellular senescence is closely associated with mitochondrial dysfunction. Sirtuin 2 (Sirt2), a member of the Sirtuin deacetylases family, plays a pivotal role in regulating energy metabolism and aging in mammals. However, its function in social insect aging remains unclear. Here, using the Eastern honey bee (Apis cerana) as a model, we demonstrate that the age-related downregulation of A. cerana Sirt2 (AcSirt2) in brain tissue is coupled with progressive mitochondrial damage, reactive oxygen...
Single Cell and Spatially Resolved Transcriptome and Immune Repertoire of Mouse Thymus During Aging Reveal Immunological Heterogeneity and Direction of Thymic Selection Pressure
The thymus is the central organ where T cells differentiate and proliferate. T cells experience the TCR recombination to generate diversity, self-antigen tolerance, and immune response. However, the spatial heterogeneity of transcriptomics and immune repertoire of the thymus during aging haven't been studied. We constructed the thymus's spatial transcriptomics and spatial immune repertoire atlas by TCR-specific amplification. The integrated multi-omics analysis of the scRNA-seq, ST-seq,...
Apiotrichum-Centered Fungal Interaction Network Disturbance Correlates With Increased Arterial Stiffness
The gut mycobiome plays an essential role in human health, yet its influence on the progression of arterial stiffness, a key feature of vascular aging, remains obscure. In this study, we aimed to investigate the involvement of intestinal fungi in the exacerbation of arterial stiffness. In total, 763 participants were invited for the brachial-ankle pulse wave velocity test to determine their status of arterial stiffness. The gut mycobiome was identified through internal transcribed spacer...
Factors Associated With Physiological Dysregulation Among US Adults Aged 45 Years and Older: A Nationally Representative Study
CONCLUSIONS: Female sex and physical activity were associated with lower physiological dysregulation, whereas higher BMI was associated with greater dysregulation. These findings underscore the importance of sex differences and modifiable lifestyle factors, particularly physical activity and adiposity in multisystem physiological burden among older US adults.
Transcriptomic landscape of human cardiac aging: identification of cardioselective age-associated genes and predictive modeling
Age is a major risk factor for cardiovascular disease, yet the molecular mechanisms underlying human cardiac aging are not fully understood. Using bulk RNA sequencing data from the Genotype-Tissue Expression (GTEx) project, we identified cardiac age-associated genes by intersecting transcripts significantly correlated with age in both the atrial appendage and left ventricle, while excluding those similarly altered in skeletal muscle. Among these, 131 genes were positively correlated with age,...
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