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CONCLUSIONS: Tailoring intervention strategies according to specific health statuses of older adults may prevent and delay CF onset and facilitate recovery from MCI and PF.

Microglia-driven dysregulation has emerged as a significant underlying mechanism in many neurodegenerative diseases, such as age-related macular degeneration (AMD) and Alzheimer's disease (AD). Although both brain and retinal microglia originate from the yolk sac, it is uncertain whether they share molecular similarities or genetic and molecular foundations related to neurodegenerative diseases. In this study, we examine the transcriptomic and epigenetic profiles of retina and brain microglia...

A hallmark of Alzheimer's disease (AD) is the accumulation of extracellular amyloid-β plaques in the brain. Amyloid-β is a 40-42 amino acid peptide generated by proteolytic processing of amyloid precursor protein (APP) via membrane-bound proteases. APP is a transmembrane protein, and its trafficking to sites of proteolysis represents a rate-limiting step in AD progression. Although APP processing has been well-studied, its trafficking itinerary and machinery remain incompletely understood. To...

A growing body of evidence shows that epileptic activity is frequently observed in patients with Alzheimer's disease (AD), implicating underlying excitatory-inhibitory imbalance. The distinction of whether the AD-epileptic phenotype represents a subset of patients or an underdiagnosed manifestation holds major therapeutic implications. Here, we quantified the excitatory-inhibitory imbalance in AD patients using magnetoencephalography and examined the relationships to AD...

T cell dysfunction with age underlies an increased incidence of cancer in elderly individuals; however, how T cell aging is triggered in the tumor microenvironment is unclear. Here, we show that an age-associated reduction in adipocyte-derived leptin contributes to the accumulation of tumor-infiltrating senescent CD8^(+) T cells. Single-cell profiling of human and mouse cancer tissues reveals that the frequency of intratumoral senescent CD8^(+) T cells increases with age, leading to a weak...

TANK-Binding Kinase 1 (TBK1) is involved in autophagy and immune signaling. Dominant loss-of-function mutations in TBK1 have been linked to Amyotrophic Lateral Sclerosis (ALS), Fronto-temporal dementia (FTD), and ALS/FTD. However, pathogenic mechanisms remain unclear, particularly the cell-type specific disease contributions of TBK1 mutations. Here, we show that deleting Tbk1 from mouse motor neurons does not induce transcriptional stress, despite lifelong signs of autophagy deregulations....

Declining oocyte quality is the major contributor to female subfertility in aged mammals. Currently, there are no effective interventions to ameliorate aged oocyte quality. Here we found that oocytes at metaphase I from the cumulus-oocyte complexes of aged mice showed reduced cortical F-actin and lower levels of mevalonate (MVA) pathway metabolites, including MVA, farnesyl pyrophosphate (FPP) and geranylgeranyl pyrophosphate. We further showed that MVA supplementation improved FPP levels,...

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CONCLUSION: Our findings indicate that a substantial proportion of older adults experience digital exclusion, particularly in China. Digital exclusion demonstrates a positive association with loneliness, suggesting that enhancing digital inclusion may serve as a critical strategy for alleviating loneliness and mitigating psychological distress in ageing populations.

Current obesity classifications may not adequately reflect age- and gender-specific risks in diverse populations. In a prospective cohort study of 166,285 Chinese adults aged ≥40 years without prior cardiovascular disease (CVD) or cancer, we evaluate optimal thresholds of body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR) for predicting incident CVD and all-cause mortality. We observe monotonically increasing dose-response associations of BMI, WC, and WHR with CVD risk...

Reactive oxygen species (ROS) influence cell proliferation and fate decisions by oxidizing cysteine residues (S-sulfenylation) of proteins, but specific targets and underlying regulatory mechanisms remain poorly defined. Here, we employ redox proteomics to identify cell-cycle-coordinated S-sulfenylation events and investigate their functional role in proliferation control. Although ROS levels rise during cell cycle progression, the overall oxidation of the proteome remains constant, with dynamic...

CONCLUSIONS: Aerobic exercise mitigates AGEs-induced muscle deterioration through molecular and structural improvements. SAF and CML may serve as noninvasive biomarkers of functional decline in older adults. These findings highlight the potential of exercise to counteract sarcopenia associated with AGEs accumulation.

Exposure to infectious disease in early life may have long-term ramifications for health and lifespan. However, reducing pathogen exposure may not be uniformly beneficial. The rise of modern sanitation and reduction of infectious diseases has been implicated in increasing levels of allergy and immune dysregulation: termed, the "hygiene hypothesis." This study leverages quasi-experimental variation from combining precampaign hookworm exposure with the Rockefeller Sanitary Commission's deworming...

How societies remember the dead can reveal what people value in life. We analyzed 38 million obituaries from the United States to examine how personal values are encoded in individual and collective legacies. Using Schwartz's theory of basic human values, we found that tradition and benevolence dominated legacy reflections, while values like power and stimulation appeared less frequently. Major cultural events-the terrorist attacks of September 11th, the 2008 financial crisis, and the COVID-19...

Parkinson's disease (PD) is characterized by the death of substantia nigra pars compacta (SNc) dopamine (DA) neurons, but the pathophysiological mechanisms that precede and drive their death remain unknown. The activity of DA neurons is likely altered in PD, but we understand little about if or how chronic changes in activity may contribute to degeneration. To address this question, we developed a chemogenetic (DREADD) mouse model to chronically increase DA neuron activity and confirmed this...

Ageing of the haematopoietic system is characterized by phenotypic and functional impairments that are driven by alterations of haematopoietic stem cells and of the bone marrow niche. Haematopoietic stem cells are responsible for the production of all the different cell types that constitute the blood, and their maintenance and differentiation must be tightly regulated during the whole life of an organism. Exciting new data emphasize that central aspects of blood ageing, ranging from...

Megan O’Rourke hopes to be a voice for science, also touts her blue-collar roots