Aging & Longevity

CONCLUSION: Our findings suggest that regular AGPA is associated with markers of slower neurovascular aging in older individuals. AGPA induces a combination of general physical activity-related and specific AGPA-related effects; moreover, it may offer similar or even greater benefits than physical activity alone. Therefore, habitual AGPA may serve as an effective preventive strategy for neurovascular aging.

Aging is a natural physiological process that may be accompanied by pathological changes, particularly in the brain. Iron is an essential trace element supporting various physiological functions and maintaining cellular homeostasis. However, iron levels tend to increase in certain brain regions of older adults and are associated with the development of neurodegenerative diseases. Despite this association, the causal relationship between aging, iron accumulation, and neurodegenerative diseases...

Women's reproductive health plays a pivotal role in both longevity and the aging process. We conduct Mendelian randomization (MR) and observational analyses to investigate these relationships. Univariate MR analyses reveal that older age at first birth, later menarche, higher estradiol, and sex hormone-binding globulin (SHBG) increase longevity, while pre-eclampsia liability decreases longevity. Older ages at first birth and at first sexual intercourse are associated with lower DNAmGrimAgeAccel,...

Despite ample research on cognitive aging, it is still largely unknown whether cognition is organized in a distinct manner, with different cognitive domains and subcomponents interrelating with each other. It is also unknown whether this cognitive organization is stable or changes with increasing age. Following the PRISMA guidelines statement, we conducted a systematic review of multivariate studies of cognitive aging with the aim to identify a potential cognitive organization in healthy aging....

Senescence contributes to the pathology of abdominal aortic aneurysm (AAA); however, the regulation of senescence in AAA remains unclear. Here, we sought to determine the role of gasdermin-E (GSDME)-dependent non-canonical pyroptosis in AAA. GSDME-dependent non-canonical pyroptosis is activated in the lesioned vascular walls of mouse models and patients with AAA. GSDME deficiency inhibits vascular senescence and AAA progression. Combined analyses of single-cell RNA sequencing (scRNA-seq), bulk...

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...

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...