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Population ageing is a global phenomenon with significant implications for public health. Research has highlighted a relationship between gut microbiota, inflammatory cytokines, and ageing, yet the underlying causal mechanisms remain elusive. This study uses Mendelian randomization (MR) analysis to investigate causal relationships between gut microbiota, inflammatory cytokines, and ageing phenotypes. We leveraged the summary statistics of gut microbiota (n = 5959), circulating inflammatory...

The genetics of human longevity has been primarily studied using classical methods developed in genome-wide association studies. With the recent advances in paleogenomics, it is now possible to investigate to what extent ancient population ancestries contribute to complex traits. In this study, we explored the role of ancient genetic components in human longevity by focusing on the Italian Peninsula, whose genetic heritage includes several past genetic ancestries that have contributed to the...

Women experience more pronounced lipidomic changes with aging than men, which may contribute to the higher rates of Alzheimer's disease seen in postmenopausal women. Our earlier findings showed that transplantation of young ovarian somatic tissues or cells produced positive health-enhancing results in postreproductive females. In the current experiments, we looked to find key health-enhancing ovarian cells and pathways involved in this phenomenon. We conducted physiological and molecular...

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Alzheimer's disease (AD), first identified by Dr. Alois Alzheimer in 1906, has evolved from a rare presenile dementia to a global health crisis affecting over 58 million people as of 2020, with projections reaching 152 million by 2050. Manuscript offers a comprehensive overview of AD, tracing its historical origins, epidemiological trends, pathophysiological mechanisms, diagnostic advancements, and therapeutic strategies. The pathogenesis of AD is multifactorial, involving amyloid-β plaque...

White matter hyperintensities (WMH) are a magnetic resonance imaging (MRI) sign associated with cognitive complaints in the Alzheimer's Disease (AD) continuum, including the pre-dementia steps. Cardiovascular and neurodegenerative pathophysiology have been postulated as relevant factors in the origin of WMH in AD. However, this evidence comes mainly from northern global populations, where the epidemiological profile differs from other geographical regions. This study explores the relationship...

Large-scale single-cell atlases have revealed many aging- and disease-associated cell types, yet these populations are often underrepresented in heterogeneous tissues, limiting detailed molecular analyses. To address this, we developed EnrichSci-a scalable, microfluidics-free platform that combines hybridization chain reaction RNA fluorescence in situ hybridization (FISH) with combinatorial indexing to profile single-nucleus transcriptomes of target cell types with full gene-body coverage....

Cellular systems governing protein folding depend on functional redundancy and diversification to maintain proteostasis. Here, using Caenorhabditis elegans, we show two homologous ER-resident HSP70 chaperones, HSP-3 and HSP-4, have overlapping and distinct roles in ER proteostasis and organismal physiology. Their expression and function vary by tissue, age, and stress, impacting ER stress resistance, reproduction, body size, and lifespan. We also find HSP-3 and HSP-4 uniquely regulate dietary...

Intrinsic capacity (IC), which comprises all physical and mental capacities of individuals, is a key component in the World Health Organization's healthy aging framework. A validated IC measure is lacking in India, the most populous country in the world. The aim of this study is to develop an IC measure in older Indian adults using 60,591 participants aged ≥45 years from the Longitudinal Ageing Study in India. Confirmatory factor analysis incorporated 14 items of cognitive, locomotor,...

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality worldwide. The E3 ubiquitin ligase WWP2 has emerged as a critical regulator of tumor pathogenesis through its modulation of substrate ubiquitination. However, its specific mechanistic role in HCC remains poorly understood. In this study, we found that WWP2 was significantly up-regulated in HCC patients and associated with poor prognosis. Lentivirus-mediated knockdown of WWP2 induced cellular senescence and suppressed...

The perovskite solar cells (PSCs) achieve notable advances in stability under humidity, light, and heat stress. However, PSCs are still susceptible to reverse-bias degradation, mainly due to the inevitable iodide ions migration. Herein, we reveal the irreversible cross-layer migration of iodide ion (I^(-)) within PSCs under reverse bias, which contributes to the device performance failure. Further, we innovatively construct an electrostatic repulsion with I^(-) at the perovskite interface, which...

Skin is both the most visible and most environmentally exposed organ, with apparent aging phenotypes. DNA methylation clocks faithfully capture the progression of aging, but so far have been limited to training on abundant in vitro material or invasively collected samples to generate narrow methylomes using microarray platforms. Here, we demonstrate that skin biological age can be measured directly from a person's face with superior accuracy, using non-invasive tape-stripping. We developed two...

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Microglial capacity to adapt to tissue needs is a hallmark feature of these cells. New studies show that mitochondria critically regulate the phenotypic adaptability of macrophages. To determine whether these organelles play similar roles in shaping microglial phenotypes, we generated transgenic mouse crosses to accurately visualize and manipulate microglial mitochondria. We find that brain-region differences in microglial attributes and responses to aging are accompanied by regional differences...

The EAT-Lancet diet has been recently recommended for its potential health and environmental benefits. Here, leveraging data from the UK Biobank, we performed a comparative analysis to examine the associations of adherence to the EAT-Lancet diet versus traditional plant-based diets with biological aging and further assess the mediating role of metabolomic signatures specific to dietary patterns. Compared with the overall or healthful plant-based diet index, higher adherence to the EAT-Lancet...

Liver-expressed antimicrobial peptide-2 (LEAP-2), the endogenous antagonist of the ghrelin receptor (GHSR1a), counterbalances ghrelin in an energy- and inflammation-dependent manner. Aging is accompanied by endocrine and immunometabolic shifts that may influence this axis. We investigated whether a short course of broad-spectrum antibiotics (vancomycin-metronidazole-neomycin-ampicillin; VMNA) alters LEAP-2 and ghrelin levels in the liver and epididymal white adipose tissue (WAT) of aged male...

CONCLUSION: The present findings emphasize that strengthening individual resilience, along with promoting social and family support and paying attention to emotional relationships, is effective in reducing loneliness in older people.

Growing evidence shows that epigenetic modification and mitochondrial dysfunction are hallmarks of aging and are associated with the development of a wide range of age-related diseases. Mitochondrial biogenesis, which is marked by mitochondrial DNA copy number (mtDNAcn), is one of the major regulations of mitochondrial function by a set of transacting elements, including mitochondrial DNA polymerase gamma (POLG), working on the mtDNA control region. In this study, we investigated the mtDNAcn and...

How do neurophysiological traits that characterize individuals evolve across the lifespan? To address this question, we analyzed task-free magnetoencephalographic recordings from over 1,000 individuals aged 4-89. We found that neurophysiological activity is more similar between individuals in childhood than in adulthood, an effect driven predominantly by arrhythmic brain activity. In contrast, periodic activity-based profiles remain reliable markers of individuality across all ages. The cortical...

INTRODUCTION: Primitive reflexes (PRs) are brainstem-mediated automatic responses that typically disappear in early life, but may reappear in older age, which may be associated with neurodegenerative processes. But the presence of PRs in cognitively healthy adults has not yet been sufficiently explored. The relationship between PRs and cognitive functioning (COG) may be influenced by modifiable factors such as physical activity (PA) and psychological resilience. This cross-sectional...