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Neuronal aggregates of Tau are a hallmark of Alzheimer's disease (AD), but more than half of the patients exhibit additional TDP-43 inclusions, while some have co-aggregates of the two proteins. The presence of such co-aggregates is associated with increased disease severity, although whether there is a causal relationship remains unclear. Here, we demonstrate that Tau and TDP-43 mutually promote each other's condensation through direct interaction in vitro, forming irregularly-shaped or...

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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 (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...

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...

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...

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...

APOE4 is the primary risk factor for Alzheimer disease (AD). Early AD pathological events first affect the neuronal endolysosomal system, which in turn causes neuronal protein aggregation and cell death. Despite the crucial influence of lysosomes upon AD pathophysiology, and that APOE4 localizes to lysosomes, the influence of APOE4 on lysosomal function remains unexplored. We find that expression of APOE4 in neuronal cell lines results in lysosomal alkalinization and impaired lysosomal function....