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AI-aided identification of dual-purpose therapeutic targets PRPF19 and MAPK9 in hepatocellular carcinoma and cellular senescence
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...
Biological aging, left ventricular dysfunction and mortality in patients with heart failure with preserved ejection fraction
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...
Transient hepatic reconstitution of trophic factors enhances aged immunity
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...
Restoring youth to old immune cells: mRNA therapy turns back the clock
No abstract
The relationship between frailty status and psychosocial indices in older Korean adults
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...
Beyond strength: dietary nitrate augments self-selected functional mobility after resistance training in middle-aged adults
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...
Multiomics insight into disease trajectories of cardiometabolic diseases and cancer
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...
Cross-sectional trends in healthy lifestyles among the oldest-old in China, 1998-2018
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.
Synergistic effects of multicomponent exercise and rTMS on sarcopenia and mild cognitive impairment in older people: a protocol for a randomized controlled trial
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...
The transaminase-ω-amidase pathway senses oxidative stress to control glutamine metabolism and α-ketoglutarate levels in endothelial cells
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...
Single-nucleus multiomics reveals the disrupted regulatory programs in three brain regions of sporadic early-onset Alzheimer's disease
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...
GPNMB, LRRK2, and lysosome exocytosis in Parkinson's
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.
GPNMB is a biomarker for lysosomal dysfunction and is secreted via LRRK2-modulated lysosomal exocytosis
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...
Titan might not have an ocean after all
A reanalysis of data from NASA’s Cassini mission suggests Saturn’s icy moon may lack the subsurface ocean presumed for a decade
Persistence and Determinants of Late-Life Depression: Results of the Nationally Representative Longitudinal German Aging Survey 2008 to 2023
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.
Genetic links between multimorbidity and human aging
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...
Multi-omic analysis of canine aging uncovers conserved aging pathways
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...
Blood-based biomarkers of Alzheimer's disease and olfactory decline over 15 years in older adults
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...
Engagement in more light physical activity and less sedentary time does not protect against age-related declines in cerebrovascular reactivity in healthy older adults
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...
Adults up to 80 years old maintain effective movement planning when facing complex body dynamics
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...