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Dementia arises from a complex interplay of biological, psychological, and sociocultural factors. However, previous large-scale studies have largely focused on biomarkers and genetics, with limited attention to the social and structural determinants of health that shape diverse aging trajectories. The Brain Resilience Study (BRS) addresses this gap by integrating multimodal biological and cognitive measures with rich demographic, psychosocial, and lifestyle data to create an open resource for...

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The proteasome is essential for cellular protein homeostasis through selective destruction of damaged and misfolded proteins. Failure of proteasome-dependent turnover accompanied by accumulation and aggregation of aberrant proteins is a hallmark of aging and late-onset neurodegenerative diseases. SKN-1A/Nrf1, a member of the NFE2L/Nrf family of transcription factors, is a master regulator of proteasome biogenesis. Through transcriptional control of proteasome subunit gene expression, SKN-1A/Nrf1...

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CONCLUSIONS: Intrinsic capacity impairment is associated with compromised HRQoL both directly and indirectly by exacerbating functional dependence. Preserving functional independence serves as a key pathway connecting intrinsic capacity to well-being. These findings highlight the imperative for integrated interventions that simultaneously bolster intrinsic capacity and support daily functional ability, tailored to diverse living environments to promote healthy aging.

An important hallmark of aging-and particularly of neurodegeneration-is the loss of proteostasis, leading to cellular stress. However, the causal mechanisms driving this loss are unclear. We show that SIRT6 has a critical role in maintaining proteostasis. Mechanistically, SIRT6 negatively regulates global translation by controlling ribosomal genes, nucleolar function and TIP5 chromatin localization. SIRT6 deletion increases nucleolar size, rRNA production and protein translation. However, the...

CONCLUSIONS: This study demonstrates that routine physical examination information could be a valuable component to incorporate into targeted assessments to screen low muscle mass among community-dwelling older adults. Building on this foundation, an interpretable machine learning approach was explored, which proves well-suited as a screening manner for low muscle mass to guide further standard assessment. Its suitability stems from superior predictive performance and operational feasibility in...

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CONCLUSIONS: Our findings suggest that PM2.5 exposure was associated with increased AD risk, primarily through direct rather than comorbidity-mediated pathways. Stroke may modestly increase susceptibility. These findings highlight the need for air quality interventions as part of dementia prevention strategies in aging populations, especially those facing overlapping environmental and clinical vulnerabilities.

Pathological progression in sporadic Alzheimer's disease (sAD) initiates with an early rise in soluble amyloid-β (Aβ), preceding plaque formation and neurodegeneration. However, the molecular event triggering this initial accumulation remains unknown. We report that phosphoglycerate dehydrogenase (PHGDH), a consistent biomarker of prodromal sAD, drives Aβ production through a previously unrecognized RNA-binding function. Specifically, PHGDH binds the 3'UTR of EIF2AK1 mRNA, enabling the physical...

Peucedanum japonicum Thunb. (PJ), also known as costal hog fennel, is an edible medicinal plant recognized for its potential health benefits. We previously demonstrated the protective effects of PJ against muscle atrophy in young mice. In the present study, we investigated whether PJ also inhibits age-related muscle loss in aged mice. PJ treatment of primary myoblasts derived from aged mice attenuated myotube diameter reduction, suppressed the expression of atrogenes, and prevented the...

Sex differences in aging are robust and ubiquitous. Demographic differences in aging generated by sex have long been recognized, but the underlying biological basis for these differences and the potential for sex-specific interventions remain understudied. To explore sex differences in the response to pro-longevity interventions, we utilized the C. elegans aging model and asked whether male lifespan and reproductive healthspan can be extended via compounds known to have pro-longevity effects in...

Dietary interventions such as caloric restriction and periodic fasting improve metabolic health and extend lifespan in preclinical models, yet individuals differ widely in their physiological responses-variation that remains poorly understood but is critical for safe and effective translation to humans. We applied a two days per week intermittent fasting (IF) regimen to 10 inbred strains from the Collaborative Cross (CC), a genetically diverse, reproducible panel ideal for dissecting genetic...

CONCLUSIONS: Our findings suggest that PM2.5 exposure was associated with increased AD risk, primarily through direct rather than comorbidity-mediated pathways. Stroke may modestly increase susceptibility. These findings highlight the need for air quality interventions as part of dementia prevention strategies in aging populations, especially those facing overlapping environmental and clinical vulnerabilities.

Researchers identify a complex that hands mimivirus control of protein synthesis in infected amoebae

Two intellectual property lawyers on why questions of AI inventorship and profit remain wide open

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CONCLUSIONS: Overall, the present study findings demonstrate that excessive sleep duration (over 10 h) is an independent predictor of increased risk of dementia among older Chinese adults. Conversely, maintaining a moderate sleep duration of 6 to 8 h appears to be a protective factor, correlating with a lower incidence of the condition.

Age-related macular degeneration (AMD) stands as a leading cause of blindness in the elderly, yet the fundamental aging processes that underpin its pathogenesis remain incompletely defined. The dysfunction of retinal pigment epithelial (RPE) cells is a central event in AMD, a process that shares key hallmarks with broader cellular aging, particularly the progressive decline in mitochondrial function. In this study, we investigated how a common environmental stressor-blue light-triggers a key...