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Tauopathies encompass a range of neurodegenerative disorders, such as Alzheimer's disease (AD) and frontotemporal lobar degeneration with tau inclusions (FTLD-tau), for which there are currently no successful treatments. Here, we show impaired glycogen metabolism in the brain of a tauopathy Drosophila melanogaster model and people with AD, indicating a link between tauopathies and glycogen metabolism. We demonstrate that the breakdown of neuronal glycogen ameliorates the tauopathy phenotypes in...

CONCLUSION: Metabolomics offers a promising approach to identify early biomarkers of frailty, balance impairment, and fall risks in older adults. The integration of metabolic profiles with clinical assessments could lead to more precise and personalized healthcare interventions, improving fall prevention strategies and frailty management. Future studies with larger cohorts are needed to validate these findings and explore the clinical utility of Metabolomics in aging-related healthcare.

Doxorubicin (DOX)-induced cardiotoxicity (DIC) poses a major threat to elderly cancer patients, often leading to severe cardiac dysfunction and complicating the outcome of cancer treatment. Autophagy is one of the core mechanisms of DIC and is considered a key therapeutic target. We analyzed the status of research in the field of autophagy in DIC via bibliometric methods. A total of 292 publications related to this topic were identified and included. Furthermore, based on included publications...

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Homelessness and chronic disease have been previously linked. We examined the bidirectional, sex-specific, relationship between homelessness and cerebrovascular disease among aging veterans seeking U.S. Department of Veterans Affairs (VA) healthcare services. A retrospective study was conducted among a cohort of 4,061,031 veterans (mean [± standard deviation] age: 68.7 [± 10.3] years; 94.6% men) followed between 2017 and 2021 and defined through linkage of VA Corporate Data Warehouse, Homeless...

Synbiotic formulations, which combine prebiotics and probiotics in their composition, have shown promise in improving brain function and cognitive performance. However, the mechanisms by which synbiotics exert their beneficial effects on memory processes, particularly in the context of aging, remain unclear. In the present study, we investigated the effects of synbiotics supplementation on memory updating (reversal learning) and extinction in adult and aged rats. We also assessed the impact of...

Inflammaging, an age-associated increase in chronic inflammation, is considered a hallmark of aging. However, there is no consensus approach to measuring inflammaging based on circulating cytokines. Here we assessed whether an inflammaging axis detected in the Italian InCHIANTI dataset comprising 19 cytokines could be generalized to a different industrialized population (Singapore Longitudinal Aging Study) or to two indigenous, nonindustrialized populations: the Tsimane from the Bolivian Amazon...

Aging is characterized by a decline in the functionality and number of stem cells across the organism. In this study, we uncovered a mechanism by which systemic inflammation drives muscle stem cell (MuSC) aging through epigenetic erosion. We demonstrate that age-related inflammation decreases monomethylation of H4K20 in MuSCs, disrupting their quiescence and inducing ferroptosis, a form of iron-dependent cell death. Our findings show that inflammatory signals downregulate Kmt5a, the enzyme...

Diapause is a long-lived state of resilience that allows organisms to outlast adversity. Caenorhabditis elegans can endure months in a fasting-induced adult reproductive diapause (ARD) and, upon refeeding, regenerate and reproduce. Here we find that mutants of ARD master regulator hlh-30/TFEB arrest in a senescence-like state during ARD and refeeding, in which germline stem cells are characterized by DNA damage, nucleolar expansion, cell cycle arrest and mitochondrial dysfunction, alongside...

Aged hematopoietic stem cells (HSCs) exhibit diminished self-renewal and myeloid-biased differentiation with a decline in hematopoiesis and adaptive immune function. However, the molecular regulation of this impaired function remains largely unknown. Here, through an in vivo CRISPR-Cas9-based screen, we uncovered clusterin (Clu) as a driver of biased differentiation. Clu is upregulated in aged HSCs, and its knockout diminishes biased differentiation. Clu promotes mitochondrial hyperfusion by...

β-Amyloid (Aβ) is generated from the amyloid precursor protein (APP) through sequential cleavage by β-site APP-cleaving enzyme 1 (BACE1) and γ-secretase, where BACE1 acting as the rate-limiting enzyme. Elevated BACE1 levels in the brains of Alzheimer's disease (AD) patients implicate that dysregulated BACE1 expression is crucial to AD pathogenesis. However, the underlying regulatory mechanisms remain unclear. Here, we identified that the G protein subunit β5 gene (Gnb5), a component of the G...

Sarcopenia, or age-related muscle dysfunction, contributes to morbidity and mortality. Besides decreases in muscle force, sarcopenia is associated with atrophy and fast-to-slow fiber type switching, which is typically secondary to denervation in humans and rodents. However, very little is known about cellular changes preceding these important (mal)adaptations. To this matter, mitochondria and the sarcoplasmic reticulum are critical for tension generation in myofibers. They physically interact at...

Aging features a gradual decline in genomic integrity, epigenetic fidelity, and cellular homeostasis, driving the onset of chronic pathologies such as cancer, neurodegeneration, and metabolic disease. Growth arrest and DNA damage-inducible 45 alpha (GADD45α) functions as a pivotal stress-response mediator, coordinating DNA repair, cell-cycle arrest, oxidative stress defence, mitochondrial quality control, and chromatin remodeling. Researchers have extensively studied GADD45α in tumor...

Cellular senescence contributes to cognitive decline in brain diseases. In dyslipidemic and atherosclerotic LDLr^(-/-);hApoB100^(+/+) (ATX) mice-a model exhibiting vascular dysfunctions and cognitive impairment-the role of senescence was investigated by targeting angiopoietin-like 2 (angptl2), a senescence marker. Adult ATX mice of both sexes received AAV1-sh-angptl2; cognition was assessed via the Morris Water Maze, cerebrovascular functions were evaluated in vitro and in vivo and hippocampal...

Somatic mitochondrial DNA (mtDNA) mutations are implicated as important drivers of ageing and age-related diseases. Their pathological effect can be counteracted by increasing the absolute amount of wild-type mtDNA via moderately upregulating TFAM, a protein important for mtDNA packaging and expression. However, strong TFAM overexpression can also have detrimental effects as it results in mtDNA hypercompaction and subsequent impairment of mtDNA gene expression. Here, we have experimentally...

A stable caregiving environment early in life is essential for children's development, and disruptions have the potential to impact biological processes. Using data from the Bucharest Early Intervention Project, we examined a developmental cascade model in which shifts in pubertal tempo following early caregiving disruptions come at an epigenetic cost. Among 115 individuals, all of whom experienced severe deprivation early in life, we tracked caregiving disruptions across childhood; assessed...

BackgroundSocial frailty has not been studied in the Philippines, a Southeast Asian country with distinct sociocultural characteristics.ObjectiveTo (i) develop and validate the Social Frailty Index-Philippines (SFI-Phil), using all-cause mortality (up to 4 years) as the outcome and (ii) evaluate performance of SFI-Phil across age, sex, and residence.MethodsPerforming regression analyses on baseline and 4-year follow-up data from 5153 older adults aged 60+ from the nationally representative...

INTRODUCTION: Osteoarthritis (OA), a prevalent musculoskeletal condition, is associated with an increased risk of falls. Maintaining posture relies on visual, vestibular, and proprioceptive inputs, but these systems can be compromised due to aging or disease, heightening fall risk. Such impairments may result from neuromuscular decline and reduced cognitive or visuospatial processing abilities. This study aimed to investigate prefrontal cortical (PFC) activation patterns during clinical sensory...

Hutchinson-Gilford progeria syndrome (HGPS) is a rare genetic disorder characterized by premature aging and primarily caused by the accumulation of progerin, a mutant form of lamin A. Although the effects of progerin on multiple tissues have been previously studied, its impact on brain development is not completely understood. We established cortical organoids derived from HGPS patient-induced pluripotent stem cells (iPSCs) from patients with HGPS to investigate the role of progerin in the...