Aging & Longevity

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.

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.

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,...

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...

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...

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.

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.

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...

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,...

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...

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...

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...

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...

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.

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...

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....

A receptor for glycation end products (RAGE) plays a key role in the pathogenesis of many chronic diseases associated with aging. Acting as a multi-ligand sensor, RAGE is able to bind a wide range of stimuli, which fuels inflammation. This makes it a key link between garb-aging and inflammaging. We propose that RAGE functions as the missing molecular link between garb-aging, the progressive buildup of biological waste, and inflammaging, the chronic inflammatory state that drives degenerative...

Genetic information in cells flows from DNA to RNA to proteins, which form molecular machines. During normal ageing, cell intrinsic and environmental factors alter this flow of information by damaging DNA in cells, including postmitotic neurons. Damage to DNA is associated with age-related neurodegenerative diseases such as Alzheimer's disease (AD). We previously reported an increase in DNA repair mechanisms in a fly model of AD. However, the causal mechanisms underlying somatic mutations in AD...

Sortilin (SORT1) is a lipoprotein receptor that shows genome-wide association with hypercholesterolaemia, explained by its ability to control hepatic output of lipoproteins. Although SORT1 also shows genome-wide association with Alzheimer disease and frontotemporal lobe dementia, the most prevalent forms of age-related dementias, sortilin's contribution to human brain lipid metabolism and health remains unclear. Here we show that sortilin mediates neuronal uptake of polyunsaturated fatty acids...

Osteoarthritis (OA) is the most common age-induced degenerative joint disease associated with synovial inflammation, subchondral bone remodeling, and cartilage degradation. One of the significant emerging causes of OA progression is senescent cell accumulation within the joint compartment during lifespan. Currently, there are no therapeutic approaches nor stratification tools that rely on the senescence burden in OA. In this study, we identified the b-series ganglioside 3 (GD3) as new senescent...