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Hepatocellular carcinoma (HCC) is one of the most prevalent and malignant forms of primary liver cancer, with limited therapeutic options and a poor prognosis. Cellular senescence contributes to the progression of chronic liver disease while creating a microenvironment that supports tumor growth. This study aims to identify dual-purpose therapeutic targets for HCC treatment and cellular senescence intervention, potentially leading to more effective therapeutic strategies. Utilizing the AI-driven...

Accelerated biological aging (BA) is linked to adverse cardiovascular events, but its role in heart failure with preserved ejection fraction (HFpEF) remains unclear. We analyzed 1,727 HFpEF patients from RED-CARPET Study (ChiCTR2000039901), assessing BA using Klemera-Doubal and PhenoAge methods. During a median 4.9-year follow-up, 321 all-cause and 180 cardiovascular deaths occurred. After full adjustment, per 1-SD increase in BA acceleration showed significantly higher risk of all-cause...

Ageing erodes human immunity, in part by reshaping the T cell repertoire, leading to increased vulnerability to infection, malignancy and vaccine failure^(1-3). Attempts to rejuvenate immune function have yielded only modest results and are limited by toxicity or lack of clinical feasibility^(1,3-5). Here we show that the liver can be transiently repurposed to restore age-diminished immune cues and improve T cell function in aged mice. These immune cues were found by performing multi-omic...

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Frailty is a heightened vulnerability to physiological stressors caused by cumulative physiological decline over a lifespan. Psychological issues (depression and stress) and social problems (such as loneliness and social isolation) serve as potential risk factors for unfavorable comorbidities, including frailty, cardiometabolic disorders, and unexpected mortality. In this study, we aimed to elucidate the relationship between frailty and psychosocial factors in an aging population. The...

This study aimed to assess whether dietary nitrate supplementation with resistance training (RT) augments gait performance and functional mobility in inactive middle-aged and older adults. We hypothesized that combining nitrate-rich beetroot juice (BRJ) with RT would yield improvements in gait and functional mobility compared to RT with nitrate-depleted beetroot juice placebo (PLA) supplementation. In this 12-week, randomized, double-blind, placebo-controlled pilot trial, 28 healthy, inactive...

Multimorbidity of cardiometabolic disease (CMD) and cancer is a growing but understudied global challenge in an aging world. Here, we perform multistate analysis in 429,555 UK Biobank participants to investigate transition patterns, identify multiomics signatures, and construct prediction models from baseline to single and multiple morbidities. During a median follow-up of 15 years, 105,903 participants develop single morbidity and 15,088 develop multimorbidity of CMD and cancer. Participants...

CONCLUSION: The findings suggest that targeted interventions are needed to promote physical activity and rural-urban disparities in healthy lifestyles should be addressed among the oldest-old Chinese.

BACKGROUND: Sarcopenia and cognitive impairment (CI) are major contributors to disability in older people, significantly reducing quality of life and imposing a substantial burden on healthcare systems. Sarcopenia accelerates cognitive decline through mechanisms such as chronic inflammation, mitochondrial dysfunction, and disruption of the muscle-brain axis. Conversely, CI impairs motor planning and daily functioning, further exacerbating muscle loss and physical deterioration. Previous studies...

Oxidative stress is a major driver of cardiovascular disease; however, the fast changes in cellular metabolism caused by short-lived reactive oxygen species (ROS) remain ill-defined. Here, we characterized changes in the endothelial cell metabolome in response to acute oxidative challenges and identified novel redox-sensitive metabolic enzymes. H(2)O(2) selectively increased the amount of α-ketoglutaramate (αKGM), a largely uncharacterized metabolite produced by glutamine transamination and an...

Sporadic early-onset Alzheimer's disease (sEOAD) represents a substantial but less-studied subtype of Alzheimer's disease (AD). Here, we generated a single-nucleus multiome atlas derived from the postmortem prefrontal cortex, entorhinal cortex, and hippocampus of nine individuals with or without sEOAD. Comprehensive analyses were conducted to delineate cell type-specific transcriptomic changes and linked candidate cis-regulatory elements (cCREs) across brain regions. We prioritized eight...

When two genes linked to increased Parkinson's risk converge on a lysosome, LRRK2 mutation enhances lysosomal release of soluble GPNMB potentially contributing to synuclein pathology.

Genome-wide association studies have identified Glycoprotein Nmb (GPNMB) as a risk factor for Parkinson's disease. The risk allele increases GPNMB transcription and GPNMB protein levels in the CSF highlighting GPMNB as a potential biomarker for Parkinson's disease. However, a lack of knowledge of GPNMB's function and mechanism of secretion has hindered an interpretation of secreted GPNMB levels. In this study, we assessed the mechanism of GPNMB secretion by macrophages, the primary cell type...

A reanalysis of data from NASA’s Cassini mission suggests Saturn’s icy moon may lack the subsurface ocean presumed for a decade

CONCLUSIONS: DS are common in later life and are frequently persistent. Minor DS often persist or worsen, underscoring their role as a key risk factor. Major DS frequently remits only partly. Early, targeted interventions could be informed by modifiable determinants that may also help to allocate scarce mental health resources effectively.

The growing epidemiological burden of multimorbidity among older adults underscores an urgent need to develop interventions that can address multiple age-related diseases (ARDs) at once. Yet, the biological mechanisms driving their co-occurrence remain poorly understood. In this study, we conducted a multivariate genome-wide association analysis to dissect the shared genetic architecture of five common ARDs: heart attack, high cholesterol, hypertension, stroke, and type 2 diabetes. We defined...

Aging is a complex biological process characterized by molecular changes across multiple biological scales. While these alterations have been extensively studied in humans and rodents, the molecular changes associated with aging in dogs remain underexplored despite their relevance as a model for human aging. In this study, we profiled gene expression (n = 16,273 genes) and protein abundance (n = 2041 proteins) in whole blood and blood plasma from 40 laboratory beagles across young (3-5 years...

Olfactory impairment is common in older age and is a known early feature of several dementia diseases. Blood-based biomarkers of Alzheimer's disease (AD) now offer a scalable method for detecting pathophysiological mechanisms related to olfactory decline in the general population. However, few studies have examined how these biomarkers relate to long-term olfactory trajectories. Most existing work has been limited to cross-sectional settings. In this population-based study, we used biomarker...

Decreased resting cerebral blood flow and cerebrovascular reactivity (CVR) are important age-related factors associated with an increased risk of stroke or dementia. However, these declines may be exaggerated by a sedentary lifestyle or blunted by engaging in more aerobic-based physical activity. The objective of the present project was to explore differences in resting middle cerebral artery velocity (MCAv), CVR, moderate-to-vigorous intensity physical activity (MVPA), light-intensity physical...

Aging significantly impacts motor performance, especially in multi-joint movement tasks where the nervous system needs to adequately coordinate mechanical interactions between joints. Effective coordination of multiple joints relies on intact feedforward control to predict movement dynamics in the initial phase of the movement, and on feedback control to fine-tune the execution in the final phase. The effect of aging on these specific control mechanisms remains controversial. Here, we...