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Synaptic dysfunction exists before symptoms occur in Parkinson's disease, and restoring synaptic function as a promising therapeutic approach. Brain-derived neurotrophic factor serves as a key neuroregulatory factor in regulating synaptic function. Studies have shown that the protein levels of brain-derived neurotrophic factor is low in Parkinson's disease mice. However, repetitive transcranial magnetic stimulation (rTMS) can mitigate this decline. We explored the protective role of rTMS on...

Functional decline of the central nervous system (CNS) is driven by the breakdown of the blood-brain barrier (BBB) and attendant inflammation, all hallmarks of age-related neurodegeneration. Despite intense interest in how the cyclic GMP-AMP synthase (cGAS)-stimulator of interferon genes (STING) pathway impacts neurodegenerative processes in aging, its role in shaping these features of CNS fate during physiological aging remains unclear. Here, using physiologically aged mice, we uncovered an...

CONCLUSIONS AND IMPLICATIONS: About half of older adults exhibit domain-specific deficits, suggesting tailored interventions are essential. Profile 5 needs comprehensive strategies, whereas orientation-focused training could benefit profiles 2, 3, and 4. Demographic factors-particularly age, ethnicity, and income-should guide customization to enhance intervention participation and adherence.

Although cancer treatment strategies have made considerable progress in recent decades, the challenge of selectively killing tumor cells while minimizing damage to healthy tissue remains. Radiotherapy (RT) continues to be crucial for tumor growth control when combined with surgery, chemotherapy, and immunotherapy. RT effectiveness depends on factors such as cancer type, tumor features, and the choice of external or internal treatment. Given its non-invasive nature and low systemic toxicity, RT...

Neuronal loss is the ultimate driver of neural system dysfunction in Alzheimer's disease (AD). We used single-nucleus RNA sequencing and neuropathological phenotyping to elucidate mechanisms of neurodegeneration in AD by identifying vulnerable neuronal populations and probing for their differentially expressed genes. Evidenced by transcriptomic analyses and quantitative tau immunoassays of human AD and non-AD brain tissue, we identified a neuronal population especially vulnerable to tau...

Although animal studies have linked cellular senescence to the pathogenesis and complications of type 2 diabetes mellitus (T2DM), there is a paucity of corroborating data in humans. Thus, we measured a previously validated marker for senescent cell burden in humans, T-cell expression of p16 mRNA, along with additional biomarkers, to compare the senescence phenotypes of postmenopausal control (lean, N = 37) and T2DM (N = 27) participants. To control for effects of obesity alone, we included a...

A healthy nervous system is reliant upon an efficient transport network to deliver essential cargoes throughout the extensive and polarised architecture of neurons. The trafficking of cargoes, such as organelles and proteins, is particularly challenging within the long projections of neurons, which, in the case of axons, can be more than four orders of magnitude longer than cell bodies. It is therefore unsurprising that disruptions in axonal transport have been reported across neurological...

Population aging increases the risk of falls, particularly among postmenopausal women, which can negatively impact their quality of life. Research suggests that multifactorial exercise programmes can help reduce this risk. This study evaluates the effectiveness of an exercise program based on Adapted Utilitarian Judo (JUA) in enhancing older adults' ability to safely manage falls; in this study called "fall competence". Fall competence can be defined as having the knowledge how to fall safely,...

Spermidine is a natural polyamine found in living organisms. In human, the level of spermidine declines with aging. Emerging lines of evidence indicates that supplementation of spermidine favors the improvement of memory performance and cognition function. In this article, recent findings regarding the metabolism of spermidine under pathophysiological conditions are discussed. This review emphasizes the recent mechanistic insights into the memory- and cognition-facilitating effects of...

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Senescent cells accumulate with aging and are associated with several age-associated diseases and functional declines. Eliminating senescent cells with senolytics improves aging phenotypes in mouse models and may improve the health of people with chronic diseases. To date, very few senotherapeutic (senolytics and senomorphics) compounds have been identified. In a recent study, we reported that gingerenone A (GinA) has a senolytic effect via mechanisms including the activation of caspase-3...

People constantly decide how much time to invest in rewarding activities. Foraging tasks assess this decision-making by measuring when individuals switch between contexts. People typically perform suboptimally in these tasks, largely due to overstaying, but it remains unclear whether this tendency changes with age independently of cognitive abilities and mental health factors. Previous research showing increased sensitivity to the opportunity cost of time in older adults predicts less...

Sarcopenia, a condition characterized by the loss of muscle mass and function with aging, is linked to various health issues including diabetes and increased risk of falls and fractures. Currently, there is no FDA-approved treatment exists for sarcopenia. Citrinin, a natural compound present in daily dietary sources such as grains, has not been well characterized for its biological effects on muscle aging. Here, we found that citrinin exhibits beneficial effects in delaying muscle aging in both...

Using multiple sources, we provide the conceptual justification and statistical support for a multimorbidity outcome associated with obesity-related conditions, which we term the Health Conditions Index (HCI). This index was designed to capture the health effects of multi-year studies of caloric restriction for older adults with BMIs in the overweight or obesity classification. We used a subset of participants in the Health, Aging and Body Composition Cohort Study to evaluate multiple aspects of...

CONCLUSION: Addressing deficiencies in nighttime care coordination, improving access to comprehensive patient information, and strengthening communication pathways between healthcare providers are essential steps in improving interprofessional collaboration to strengthen prehospital care of older patients with complex care needs.

CONCLUSION: This MR study uncovered significant causal relationships between blood cell traits such as eosinophil counts, MCV, and lymphocyte counts, with aging indicators. Monitoring these traits in routine blood tests can provide valuable insights for assessing age-related health risks and promoting healthy aging.

Mechanisms underlying the dynamic relationships of viral infections and neurodegeneration warrant examination. Using a community-based cohort of older adults, the current study characterized the neurocognitive (cognitive functioning, brain volumes, Alzheimer's disease positron emission tomography, and plasma biomarkers) and plasma proteomic (7268 proteins) profiles of four common coronavirus and six herpesvirus antibody titers. Genetic inference techniques demonstrated the associations between...

DNA methylation plays a fundamental role in regulating transcription during development and differentiation. However, its functional role in the regulation of endothelial cell (EC) transcription during state transition, meaning the switch from an angiogenic to a quiescent cell state, has not been systematically studied. Here, we report the longitudinal changes of the DNA methylome over the lifetime of the murine pulmonary vasculature. We identified prominent alterations in hyper- and...

CONCLUSIONS: Higher age and lower education at baseline were predictors of cognitive and functional deficits after 9 years, whereas frailty was not. Further longitudinal studies should be conducted to elucidate the factors predicting cognitive and functional decline in low-and middle-income countries.

We investigated the molecular mechanisms of exercise adaptations in human muscle by integrating genome, methylome, transcriptome, and proteome data from over 1,000 participants (2,340 muscle samples). We identified distinctive signatures associated with maximal oxygen consumption (VO(2max)), and multi-omics integration uncovered five key genes as robust exercise markers across layers, with transcription factors functioning as activators, synergizing with DNA methylation to regulate gene...