Aging & Longevity

Macrophage fate decisions during infection are commonly framed as receptor-proximal transcriptional choices. We propose that the functional outcome results from a "kinetic race," a dynamic proteostatic competition among protein synthesis, post-translational modifications (PTMs), and degradation. Building on experimental evidence of infection-induced proteostasis, we outline a conceptual "turnover-first" framework. In this model, we hypothesize that the ubiquitin proteasome system (UPS),...

Glucagon-like peptide-1 (GLP-1) receptor agonists have attracted interest as gerotherapeutics, yet clinical-trial evidence for their effects on biological aging is lacking. We report a post hoc exploratory epigenetic age analysis of a 32-week, randomized, double-blind, placebo-controlled phase 2b trial (NCT04019197) of semaglutide in adults with human immunodeficiency virus (HIV)-associated lipohypertrophy (semaglutide n = 45; placebo n = 39). The parent trial's primary endpoint was change in...

.The uterine decidua is a key component of the maternal-fetal interface, and its senescence may be an important contributing factor to recurrent pregnancy loss (RPL). Decidual senescence disrupts gestational homeostasis via cell cycle arrest, immune imbalance, and metabolic reprogramming, thereby potentially contributing to RPL. This review offers a new paradigm for understanding RPL etiology, with significant clinical value for improving reproductive outcomes.

Companion dogs (Canis lupus familiaris) offer a unique model for studying the gut microbiome and its relation to aging due to their cohabitation with humans, sharing similar environments, diets, and healthcare practices. Here, we present the Dog Aging Project (DAP) Precision cohort, a large population-wide study of the canine gut microbiome. This cohort encompasses over 900 dogs of diverse breeds, environments, and demographics living across the United States. Coupling fecal shotgun metagenomic...

Hydrogen peroxide (H(2)O(2)) plays various roles in the ocean, acting as a signaling molecule at low concentrations and causing oxidative stress when accumulated. Here, we use transcriptomics, genetics, and metabolomics to study H(2)O(2) dynamics in the interaction between Emiliania huxleyi algae and Phaeobacter inhibens bacteria. We find that H(2)O(2) levels rise during algal death and that bacterial H(2)O(2) production triggers this demise. In co-cultures, but not in axenic algal cultures,...

DNA methylation changes are reliable biomarkers of aging, but the driving mechanisms remain poorly understood. Here we present SCARLET (Stem Cells and Age-ReLated Epigenetic Trajectories), a parsimonious mathematical model that describes how methylation changes in blood arise and propagate through hematopoietic stem cell divisions. Using a large human cohort, we demonstrate that seemingly distinct age-related methylation patterns can be explained by a unifying mechanistic model. We show that...

CONCLUSIONS: This preliminary study demonstrates the feasibility of estimating longer-term LTC cost trajectories based on early service utilization patterns, highlighting the potential role of care managers in shaping future cost trajectories. These findings may inform efforts to enhance the fiscal sustainability and quality of Japan's LTCI system.

The Greenland shark (Somniosus microcephalus) is known for its slow metabolism and deep-sea habitat. It is thought to be the longest-lived vertebrate on Earth, with an estimated lifespan of 392 ± 120 y. Despite its remarkable longevity and unusual lifestyle, no genomic studies are yet available for this species. Here, we report a chromosome-level assembly of the Greenland shark genome, which is 5.9 Gb in size with an N50 length of 233 Mb and a completeness score of 96.7%. Our analyses of gene...

Alternations of DNA methylation occur in aging, which is regulated by DNA methyltransferases (DNMTs). In this study, we show that even though the transcription of DNMT1, the only enzyme that maintains DNA methylation in the mammalian genome, is reported to be decreased in an age-dependent manner, the decrease of Dnmt1 mRNA does not result in a decrease of its protein. Instead, DNMT1 protein is increased in aged mouse tissues, which is responsible for the methylation of genes related to...

Oxidative stress and DNA damage caused by hydroquinone (HQ) increases the aging process, whereas antioxidants encourage longer lifespan by decreasing oxidative stress, making it ideal for research on mitigation of oxidative stress induced toxicity. Our study, explored 2'-hydroxyflavanone (2HF) and quercetin (QE) effects on HQ exposed Drosophila through gut toxicity assays (trypan blue) and survivorship (Kaplan-Meier plots) along with fertility and fecundity of female flies. Effects of the...

Population-based preventive trials are rare in psychiatry, especially in an aging population, and the effects of potentially modifiable lifestyle risk factors such as diet on mental health outcomes are largely unexplored. This study aimed to estimate the effects of an anti-inflammatory diet on mental health outcomes in older adults and the potential effect of lifestyle modification. A preventive population-based target trial was emulated using data from the ASPirin in Reducing Events in the...

CONCLUSION: Based on the findings, this study recommends implementing dynamic regulatory strategies aligned with different development stages, formulating region-specific policies that account for spatial heterogeneity, and adopting targeted interventions focusing on key influencing factors, in order to systematically promote the high-quality coordinated development of healthcare services and older adults care services in China.

CONCLUSIONS: Higher daily step counts are independently associated with better quality of life, knee-specific function, and physical performance among community-dwelling Thai older adults. A target of 6,000-9,000 steps per day appears clinically meaningful and pragmatically attainable. Daily step count may serve as a practical and scalable metric to guide healthy aging strategies in Asian populations.

CONCLUSION: In this sample of older adults, worse hearing thresholds were associated with poorer performance on cognitive screening instruments and with lower hearing-related quality of life. These findings support further investigation of early hearing assessment and rehabilitation in older adults, and indicate the necessity of effective and timely auditory amplification, even in individuals with moderate hearing loss.

CONCLUSIONS: Older adults with pre-frailty and frailty value online nutrition education but require resources that are personalised, credible, and accessible across diverse learning needs. Findings highlight opportunities to embed consumer voices in resource design and provide future directions for refining the current online nutrition resource. This research contributes to evidence on consumer-informed digital nutrition education to support autonomy, dietary self-management, and healthy ageing.

Ageing represents one of the strongest non-modifiable determinants of insulin resistance (IR), a condition that extends well beyond impaired glucose handling and underling a broad spectrum of metabolic, cardiovascular, and neuropsychiatric disorders. In older adults, IR emerges from the progressive loss of physiological reserve across multiple organ systems rather than from isolated defects in insulin signalling. This narrative review examines the metabolic, inflammatory, and hormonal mechanisms...

Pregnancy-related cardiovascular complications cause substantial morbidity and account for a large proportion of maternal deaths. The relationship between maternal age and pregnancy-related cardiovascular complications remains unclear. Most prior studies categorized patients using an age threshold, and previous studies did not delineate patients' baseline cardiovascular risk versus pregnancy-specific risk. Here we show that pregnancy and the postpartum period are associated with a 7-fold higher...

Loss of host-microbiota balance promotes gut inflammation, colitis and inflammatory bowel disease. Yet, whether host or microbial factors are the critical driver of the pathology remains unclear. Here, we investigate how cardiolipin maintains metabolic fitness of regulatory T (T(reg)) cells to preserve gut-immune homeostasis. We discover that deleting the cardiolipin-synthesizing enzyme protein tyrosine phosphatase mitochondrial 1 (PTPMT1) in T cells predisposes mice to colitis due to impaired...

Disease-associated microglial states are thought to contribute to Alzheimer's disease (AD) progression, but characterizing them and their relationships to pathology remains challenging. Here we introduce CODEX-CNS-a multiplexed protein imaging technology with a custom data analysis pipeline for use in human brain samples. We profiled 704,706 cells in samples from the frontal cortex of 8 people with AD and 8 healthy controls and mapped features including blood-brain barrier, meningeal components...

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