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Tauopathies encompass a large majority of dementia diagnoses and are characterized by toxic neuronal or glial inclusions of the microtubule-associated protein tau. Tau has a high propensity to induce prion-like spreading throughout the brain via a variety of mechanisms, making tauopathy a rapid and lethal form of neurodegeneration that currently lacks an effective therapy or cure. Tau aggregation and neuronal loss associated with this pathology are accompanied by robust neuroinflammation. Innate...

Normative, longitudinal data are necessary for effective modeling of factors underlying disease processes on the brain. Large scale national and international consortium data have characterized human regional brain volume trajectories as complex and prolonged gray and white matter maturation through the third decade of life followed by progressive senescence of cortical and then subcortical gray matter. By middle age (>40 years), white matter volume is also in decline. Although rodents are the...

Apolipoprotein E4 (APOE4) is a significant risk for both familial Alzheimer's disease (AD) and sporadic AD with elusive mechanisms. Previous studies mainly focused on the role of APOE4 in familial AD, with less attention to sporadic AD. Our previous study demonstrated that blood cell-derived amyloid-β (Aβ) can enter the brain and induce AD-like pathologies, providing a novel animal model to study sporadic AD to a certain extent. The impacts of APOE4 on Alzheimer-like pathologies and cognitive...

The accumulation of senescent cells (SNCs) contributes to tissue dysfunction and age-related diseases, creating an urgent need for effective senolytic strategies. We identified a metabolic vulnerability in SNCs characterized by marked downregulation of asparagine synthetase (ASNS), rendering them uniquely dependent on exogenous asparagine (Asn). This vulnerability was exploited through combined treatment with L-asparaginase (ASNase) and autophagy inhibitors, which synergistically deplete Asn via...

Vascular aging increases the susceptibility to cardio-cerebrovascular conditions, such as atherosclerotic diseases and hypertension, the leading causes of global disability and mortality. Dietary citrate extends the lifespan of Drosophila melanogaster and Caenorhabditis elegans as well as improves the memory of mice injured by a high-fat diet (HFD); whether it alleviates vascular aging and age-related vascular diseases; however, remains unknown. Here, we showed that dietary supplementation of...

Human and murine studies reveal that innate immune cells are able to mount enhanced responses to pathogens after primary inflammatory exposure. Innate immune memory has been shown to last for months to years, longer than the lifespan of most innate immune cells. Indeed, long-lived hematopoietic stem and progenitor cells (HSPCs) serve as a cellular reservoir for innate immune memory. In this review, we summarize the evidence that innate immune memory is epigenetically encoded in HSPCs, and we...

BACKGROUND: Our understanding on how cognitive and socioemotional well-being factors interact throughout adulthood has increased remarkably over the past decades, encouraging the use of cognitively engaging leisure activities, such as music, to promote healthy ageing. Choir singing has attracted particular interest in this regard with its established benefits on socioemotional well-being. Outside the clinical context, however, the cognitive and well-being effects induced by musical activities...

CONCLUSIONS: Cognitive frailty is a consistent predictor of cardiometabolic risk across distinct populations, supporting integrated screening and prevention strategies targeting both cognitive and physical deficits in aging populations.

CONCLUSIONS: PMCC activities are associated with cognitive function improvement in middle-aged and elderly adults in China. These findings suggest that engaging in PMCC activities could serve as a potential protective factor for enhancing cognitive health in this population, providing a basis for incorporating PMCC into strategies aimed at promoting cognitive well-being and healthy aging.

Effective communication between the brain and peripheral tissues is crucial for homeostasis and health, and its impairment is a defining feature of aging. Circumventricular organs, characterized by the presence of fenestrated capillaries and absence of a blood-brain barrier (BBB), play a crucial role in controlling substance exchange between the brain and the blood. To date, adaptive changes in fenestrated vasculature in response to environmental insults remain poorly understood. In this study,...

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Science, Volume 389, Issue 6764, September 2025.