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What explains the large variation in lifespan across species? I examine an information-turnover proposition-that ancestral environmental variability should shorten captive lifespan after controlling for body mass, temperature and extrinsic mortality (P1), with a possible lineage-fate interaction (P2)-against the classical extrinsic-mortality prediction that safer niches permit longer life. I state the decision rules in advance rather than register a third-party protocol. Integrating AnAge (4,219...

Blood biomarkers are transforming Alzheimer's disease diagnostics by enabling a scalable, minimally invasive assessment of pathology. Food and Drug Administration clearances and European market certifications of different plasma tests mark a shift toward biological diagnosis in routine care. However, clinical implementation is not guided by diagnostic accuracy alone but will depend on improved patient-centered and pathway-level outcomes, including diagnostic confidence, the appropriate use of...

Obesity is a major metabolic disorder linked to neuroinflammation and cognitive decline. Beyond hypothalamic alterations, emerging evidence indicates that extra-hypothalamic regions, including the cerebellum, are vulnerable to obesity-induced neurotoxicity. This study investigated whether high-fat diet (HFD)-induced obesity causes cerebellar oxidative stress, impairs Na^(+),K^(+)-ATPase (NKA) activity, and triggers molecular features resembling brain aging in female Balb/C mice. Chronic 10-week...

Genetic evidence implicates immune dysfunction in Alzheimer's disease (AD), yet the neuroimmune mechanisms operating in human tissue remain poorly defined. Here, we establish a modular human forebrain organoid platform that systematically integrates human induced pluripotent stem cell-derived microglia and CD8^(+) T cells to reconstitute multicellular AD pathology. This system enables functional interrogation of both innate and adaptive immune components in a human-relevant context. Using this...

Multiple lysosomal stresses activate Parkinson's-linked LRRK2 kinase, and these involve the so-called "CASM" pathway to help recruit LRRK2 to lysosome surfaces. Clegg et al. (https://doi.org/10.1083/jcb.202511137) show that LRRK2, activated upon lysosome swelling caused by PIKfyve inhibition, instead relies solely on Rab GTPase binding for lysosome localization and activation.

Increased activity of leucine-rich repeat kinase 2 (LRRK2) confers Parkinson's disease risk. LRRK2 dynamically localizes to lysosomal membranes in response to various stresses, yet the mechanisms by which distinct lysosomal perturbations are communicated to LRRK2 remain unclear. Here, we show that inhibition of the lysosomal lipid kinase PIKfyve promotes LRRK2 recruitment and signaling through a pathway that requires the lysosomal chloride/proton antiporter ClC-7. ClC-7 in turn controls the...

Immune-neuron interactions play a critical role in neuroinflammatory and neurodegenerative diseases, such as Alzheimer's disease (AD), but how CD8⁺ T cells contribute to brain pathology remains poorly understood. Amyloid-β (Aβ), a hallmark of AD, is known to trigger neuronal stress and inflammation. Here, we established a human cortical organoid (hCO) model to investigate CD8⁺ T cell responses to Aβ-induced neurodegenerative stress. Aβ exposure increased neuronal expression of CX3CL1...

Alzheimer's disease (AD) is an age-related progressive neurodegenerative disorder that represents the leading cause of dementia worldwide, affecting over 50 million people. This global burden is expected to rise dramatically over the coming decades because of global population aging, representing a public health concern. Despite significant advances in understanding AD pathophysiology, early diagnosis remains challenging, emphasizing the urgent need for novel, reliable diagnostic and predictive...

CONCLUSION: In this diverse HABS-HD sample, increasing ten-year ASCVD risk was associated with greater AT(N)-V biomarker burden and poorer cognitive performance across multiple domains. These cross-sectional findings suggest that ten-year ASCVD risk may serve as a marker of co-occurring cardiovascular and brain health burden, but they do not establish causality or temporal direction.

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Baker's yeast is a long-standing model for studying mechanisms of aging. Due to asymmetric division, yeast mother and daughter cells are distinguishable, and mother cells usually cease division after 15-25 budding events. However, yeast suspensions consist predominantly of young cells. Here we investigated whether, under harsh environmental conditions, replicative aging-defined by the number of buds produced-manifests at early replicative ages. To test this, we adapted a flow-cytometry-based...

Scientists have found a promising way to protect the brain from Alzheimer’s-related damage by blocking immune cells that contribute to the destruction of neurons. In mice, the treatment preserved roughly 40% more tissue in memory centers and improved memory, even without removing harmful tau protein buildup.

A jury ruled in favor of the former Whitehead Institute scientist, dismissing accuser’s claims of sexual harassment and retaliation