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Ovarian aging plays a pivotal role in female reproductive health, with implications for treatment strategies and quality of life. However, the potential of a single pharmaceutical agent to mitigate primate ovarian aging remains largely unexplored. Our 3.3-year study in monkeys demonstrates that oral vitamin C has geroprotective effects against ovarian aging. Vitamin C diminishes key aging biomarkers, including oxidative stress and follicular depletion. Using a single-cell transcriptomic clock,...

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and...

BACKGROUND: Comprehensive, comparable, and timely estimates of demographic metrics-including life expectancy and age-specific mortality-are essential for evaluating, understanding, and addressing trends in population health. The COVID-19 pandemic highlighted the importance of timely and all-cause mortality estimates for being able to respond to changing trends in health outcomes, showing a strong need for demographic analysis tools that can produce all-cause mortality estimates more rapidly with...

BACKGROUND: Timely and comprehensive analyses of causes of death stratified by age, sex, and location are essential for shaping effective health policies aimed at reducing global mortality. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2023 provides cause-specific mortality estimates measured in counts, rates, and years of life lost (YLLs). GBD 2023 aimed to enhance our understanding of the relationship between age and cause of death by quantifying the probability of...

The discovery of non-toxic, bioresorbable silicon electronics is a major breakthrough in the fields of transient, dissolvable biomedical implants and environmental monitors, as it opens up the possibility of producing versatile components based on established semiconductor processes. However, given the limited lifespan of such electronics, it is essential to consider economical manufacturing and production strategies that reduce the unit price for commercialization. Here, we introduce a...

Aging is the most important risk factor for multiple pathologies including cardiovascular, neoplastic, metabolic and neurodegenerative diseases. Potential geroprotective strategies involve lifestyle-related, nutritional and pharmacological interventions. Recently, chalcones, a subgroup of secondary plant metabolites, have gained attention. 4,4'-dimethoxychalcone was the first chalcone to be shown to mediate geroprotection and lifespan extension across different species. Several other chalcones...

The insulin receptor entrains tissue growth and metabolism to nutritional conditions. Complete loss of function in humans leads to extreme insulin resistance and infantile mortality, while loss of 80-90% function permits longevity of decades. Even low-level activation of severely compromised receptors, for example by anti-receptor monoclonal antibodies, thus offers the potential for decisive clinical benefit. A barrier to genetic diagnosis and translational research is the increasing...

All mammalian organs depend on resident macrophage populations to coordinate repair and facilitate tissue-specific functions^(1-3). Functionally distinct macrophage populations reside in discrete tissue niches and are replenished through a combination of local proliferation and monocyte recruitment^(4,5). Declines in macrophage abundance and function have been linked to age-associated pathologies, including atherosclerosis, cancer and neurodegeneration^(6-8). However, the mechanisms that...

This study assessed relationships between age, glucose and insulin metabolism, and cognitive performance in vervet monkeys (Chlorocebus aethiops sabaeus) a valuable model for aging research. Executive function, working memory, body mass index (BMI), and glucose and insulin responses during intravenous glucose tolerance tests (IVGTTs) were assessed in 41 middle-aged to older (9.1-29.5 years), socially housed, female vervets. Cluster analyses yielded four distinct IVGTT response patterns relevant...

CONCLUSIONS: In contrast to BT, MRT appears to selectively enhance cognitive functions requiring inhibitory control and perceptual processing in older adults. Consequently, metabolic demands associated with MRT may offer additional cognitive benefits beyond the coordinative demands offered by traditional balance training.

Endocytosis generates life-essential vesicles via complex protein-lipid machinery, yet its initiation mechanisms remain elusive. Long thought to require full machinery spatiotemporal coordination to drive the flat-to-round vesicle transformations, we reveal a notably simple initiation mechanism in neuroendocrine chromaffin cells involving only the final step, the pore closure. During calcium-triggered exocytosis, calcium activates the phosphatase synaptojanin, rapidly converting PI(4,5)P(2) to...

Neuroinflammation contributes to Alzheimer's disease (AD), but the molecules and pathways that initiate inflammation are unclear. In this issue of Immunity, Song et al. demonstrate that ZBP1-RIPK1 signaling in microglia can drive AD, wherein ZBP1 is activated by left-handed Z-DNA leaking from mitochondria, presenting new molecular targets for AD therapeutics.

In psychology and neuroscience, scientific questions are often framed in terms of mental activity (e.g., cognition, emotion, and perception); however, the brain is an organ with a particular function that only it can fulfill. Converging evidence suggests that this function is allostasis: the predictive regulation of competing demands from internal bodily systems. We review evidence for a distributed allostatic system that organizes whole-brain signaling, scaffolds psychological phenomena, and...

This systematic review investigates the timeline of Alzheimer's disease (AD)-like changes in the intracerebroventricular streptozotocin (ICV-STZ) rat model, a key tool for studying sporadic, non-genetic forms of AD. Following PRISMA guidelines, we analyzed 402 studies to characterize the progression of key pathological features, including cognitive deficits, insulin resistance, neurodegeneration, neuroinflammation, oxidative stress, tau pathology, amyloid aggregation, blood-brain barrier (BBB)...

Abnormal lipid metabolism is observed in Alzheimer's disease (AD), but its contribution to disease progression remains unclear. Genetic studies indicate that microglia, the brain's resident immune cells, influence lipid processing during AD. Here, we show that microglia-the brain's resident immune cells-selectively regulate lipid accumulation that associated with disease pathology in both AD mouse models and human postmortem brains. Using lipidomics and histological analysis, we identify a...

Aging cells functionally decline and accumulate damage through poorly understood mechanisms. In this issue, Antentor et al. (https://doi.org/10.1083/jcb.202412064) find that increased vacuolar pH in older yeast cells slows clathrin-mediated endocytosis. These findings have broad implications in aging-related plasma membrane protein quality control.

Aging imposes a significant socioeconomic and healthcare burden worldwide, while effective therapy is still lacking. Impaired brain drainage and excessive accumulation of metabolites and toxins such as advanced glycation end products (AGEs) are characteristics of aging that contribute to the development of neurological disorders. Recent discoveries have highlighted the role of meningeal lymphatic vessels (MLVs) in the clearance of toxic metabolites, cells, tumors, and viruses from the brain,...

Osteoarthritis (OA) is the most common form of arthritis and a leading cause of disability in the elderly, characterized by the progressive destruction of cartilage, synovial inflammation, and subchondral bone remodeling. While mechanical stress, metabolic derangements, and systemic inflammation are recognized contributors, accumulating evidence underscores the pivotal role of impaired macroautophagy/autophagy in disease pathogenesis. Autophagy declines with age, depriving chondrocytes and...