Aging & Longevity
Association Between Herpes Zoster and Risk of Incident Fragility Fractures in US Veterans: A Matched Cohort Study
CONCLUSIONS: Veterans with HZ were at a higher risk of fragility fractures relative to Veterans without HZ, highlighting the need for improved fracture prevention among those diagnosed with HZ. Further research in non-Veteran and female populations will improve generalizability.
The microbiota-gut-brain axis in mental and neurodegenerative disorders: opportunities for prevention and intervention
The microbiota-gut-brain axis (MGBA) is increasingly recognized as a critical regulator of brain health, influencing both neurodevelopment and age-related neurological decline. Disruptions in this axis, driven by gut dysbiosis, have been implicated in the pathogenesis of a wide range of neurodegenerative and neuropsychiatric disorders. This review synthesizes current evidence linking microbiota alterations to Alzheimer's disease (AD), Parkinson's disease (PD), amyotrophic lateral sclerosis...
Matrix Stiffness Promotes DRP1-Mediated Myofibroblast Senescence to Drive Silica-Induced Pulmonary Fibrosis
Silicosis is an occupational lung disease characterized by diffuse pulmonary fibrosis resulting from inhalation of silica particles. As the disease progresses, lung tissue stiffness continuously increases, driving persistent activation and accumulation of myofibroblasts. However, whether these cells undergo senescence in response to prolonged high matrix stiffness and how such senescence impacts fibrosis progression remain unclear. Here, we established an in vitro model using decellularized lung...
Age Deceleration and Reversal Gene Patterns in Dauer Diapause
The aging process is characterized by a general decrease in physical functionality and poses the biggest risk factor for a variety of diseases such as cancer, cardiovascular diseases, and neurodegenerative disorders among others. Understanding the naturally evolved mechanisms that slow aging and rejuvenate an animal could reveal important concepts on how to prevent age-associated diseases and even revert aging. The C. elegans dauer stage is a robust and long-lived alternative developmental state...
Public views towards lifespan, healthspan, and Healthy Longevity Medicine in Singapore: a qualitative study from the HEalthy LOngevity (HELO) initiatives
CONCLUSION: Personal values and priorities were central to motivations towards healthy longevity. HLM should assess and align diagnostic and treatment plans with individual preferences to support sustainable health behaviours. The Singapore public's alignment with government policies presents an opportunity to promote HLM adoption.
The Bidirectional Casual Relationships between Chronic Inflammation and Intrinsic Capacity Decline: Insights from Mendelian Randomization Analysis
CONCLUSION: Our study provides robust evidence for bidirectional causal relationships between chronic inflammation and intrinsic capacity decline, highlighting inflammation as a potential target for interventions to promote healthy aging. Future research should explore these relationships in diverse populations and investigate therapeutic strategies to mitigate inflammation-related declines in intrinsic capacity.
Aged mice exhibit widespread metabolic changes but preserved major fluxes
Metabolic dysregulation is a hallmark of aging. Here, we investigate in mice age-induced metabolic alterations using metabolomics and stable isotope tracing. Circulating metabolite fluxes and serum and tissue concentrations were measured in young and old (20-30 months) C57BL/6J mice, with young obese (ob/ob) mice as a comparator. For major circulating metabolites, concentrations changed more with age than fluxes, and fluxes changed more with obesity than with aging. Specifically, glucose,...
Efficient active hydrogen delivery for drug-free radiation enteritis therapy in mice
Radiation enteritis, affecting over 90% of pelvic/abdominal radiotherapy patients, is primarily caused by radiation-induced reactive oxygen and nitrogen species (RONS). Active hydrogens, with broad-spectrum RONS scavenging ability, show radioprotective potential but face delivery challenges due to the intestinal mucus barrier and short lifespan. Here, we show drinkable, self-thermophoretic sodium alginate/chitosan oligosaccharide-coated hydrogenated molybdenum oxide nanomachines...
Heme and iron toxicity in the aged spleen impairs T cell immunity through iron deprivation
Mechanisms of T cell aging involve cell-intrinsic alterations and interactions with immune and stromal cells. Here we found that splenic T cells exhibit greater functional decline than lymph node T cells within the same aged mouse, prompting investigation into how the aged spleen contributes to T cell aging. Proteomic analysis revealed increased expression of heme detoxification in aged spleen-derived lymphocytes. Exposure to the heme- and iron-rich aged splenic microenvironment induced aging...
Physiological Phenotypic Aging Index and Its Association With Health, Functional, and Health Care Outcomes in Older Adults: Findings From the UK Biobank
CONCLUSIONS AND IMPLICATIONS: The PAI is a significant predictor of adverse health, functional, and health care utilization outcomes and enhances predictive accuracy. Its greater impact on multimorbidity and physical function decline in women suggests the need for sex-specific aging interventions.
Development and validation of an interpretable machine learning model for predicting intrinsic capacity decline in elderly inpatients
CONCLUSION: The Support Vector Machine model can effectively identify high-risk older hospitalized patients with decreased intrinsic capacity. Early risk identification and targeted intervention measures applied in clinical practice are helpful to improve the health level of older hospitalized patients and achieve healthy aging.
Spinal motor neuron plasticity after hindlimb unloading in aged mice and its modulation by exercise with TRPM8-mediated cutaneous stimulation
Age-related motor decline is influenced not only by muscle atrophy but also by deterioration of the neuromuscular system. However, the effects of aging and disuse on spinal motor neuron (MN) plasticity remain poorly understood. In this study, we examined how short-term hindlimb unloading (HU)-a disuse model-affects neuromuscular junction (NMJ) integrity and spinal motor neuron (MN) synaptic inputs in young (3 months) and aged (22 months) mice. We also assessed whether TRPM8-mediated skin cooling...
Religious group differences in non-communicable disease risk factors in India: A cross-sectional study of adults aged 45 and older
This study highlights the underexplored differences in the prevalence and distribution of noncommunicable disease (NCD) risk factors among Hindu, Muslim, Christian, and Sikh Indian adults aged 45 and older. Using nationally representative data from 54,601 participants in the Longitudinal Ageing Study in India (2017-2018), we investigated nine NCD risk factors by sex: hypertension, abdominal adiposity, diabetes, tobacco use, excessive alcohol consumption, physical inactivity, poor sleep hygiene,...
Weight loss aggravates obesity-induced hypothalamic inflammation in mid-aged mice
While neuroinflammation is an established response to both weight gain and aging, the hypothalamic neuroinflammatory early response to weight loss (WL) remains unknown, particularly in mid-age. Here, we questioned whether WL-induced rapid restoration of normoglycemia is mediated by the resolution of hypothalamic microgliosis in mid-aged mice. Mid-aged (1 year) mice were fed normal chow (NC) or a high-fat diet (HFD, 8 weeks), and WL was induced by a 2-week switch back to NC. Key findings were...
Translational Remodeling of the Synaptic Proteome During Aging
An important hallmark of aging is the loss of proteostasis, which can lead to the formation of protein aggregates and mitochondrial dysfunction in neurons. Although it is well known that protein synthesis is finely regulated in the brain, especially at synapses, where mRNAs are locally translated in an activity-dependent manner, little is known as to the changes in the synaptic proteome and transcriptome during aging. Therefore, this work aims to elucidate the relationship between the...
Sulforaphane improves exercise-induced NRF2 signaling in older adults: an in vivo-ex vivo approach
Redox signaling is a key mechanism of exercise-induced adaptation. However, studies have demonstrated impaired responses to acute exercise in older organisms. Adjunctive therapies to augment exercise effects may overcome these deficits. Sulforaphane (SFN), a phytochemical from cruciferous vegetables, stimulates NRF2. This study tested the hypothesis that combining acute exercise (in vivo stimulus) with ex vivo SFN treatment would induce greater NRF2 activation and signaling in older adults...
Estimation of biological age and age-related outcomes with easily accessible parameters in Chinese
Biological aging exhibits significant heterogeneity across individuals, and a precise evaluation at scale is urgently needed. Here, we developed a PCAge, based on common clinical, physiological, and laboratory indices routinely collected in primary healthcare, in the CHARLS. PCAge demonstrated strong correlations with chronological age (r = 0.86-0.88, P < 0.001) and robust performance in the prediction of mortality (C-index = 0.798) over a 10-year follow-up. Biologically older individuals (PCAge...
High-fat diet attenuates vestibular and auditory dysfunction in aged mice via macrophage-mediated anti-inflammatory mechanisms
CONCLUSIONS: HFD mitigates age-related auditory and vestibular impairments by utilizing macrophage-driven anti-inflammatory processes, potentially through polarization towards an M2 phenotype. This research offers fresh perspectives for creating specific treatments, indicating the variable therapeutic possibilities of dietary adjustments in age-related cellular damage. However, the potential metabolic consequences of HFD warrant careful consideration.
Perineuronal nets in the rodent suprachiasmatic nucleus
The circadian system maintains highly stable rhythms over the lifespan. The precision of the circadian clock emerges from the network organization of the master clock located in the suprachiasmatic nucleus (SCN). Perineuronal nets (PNNs), condensed extracellular matrix structures that are composed of chondroitin sulfate proteoglycans, help maintain synaptic connections in many brain regions after the end of critical developmental periods. We examine here if the SCN of mice, rats and hamsters...
LCN2 promotes HEI-OC1 cells senescence via activating NF-kappaB signal pathway in presbycusis
Presbycusis, or age-related hearing loss (ARHL), is a prevalent sensory disorder in the elderly, driven by genetic factors, oxidative stress, inflammation responses, and cellular senescence. Despite its significance, the molecular mechanisms underlying ARHL remain poorly defined. In this study, we employed bioinformatic analysis of public gene expression datasets to identify differentially expressed genes in ARHL. Protein-protein interaction network analysis further nominated LCN2 as a hub gene....
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