Aging & Longevity

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Interorgan communication between bone and skeletal muscle is central to human health. A dysregulation of bone-muscle crosstalk is implicated in several age-related diseases. Ageing-associated changes in endocrine, inflammatory, nutritional and biomechanical stimuli can influence the differentiation capacity, function and survival of mesenchymal stem cells and bone-forming and muscle-forming cells. Consequently, the secretome phenotype of bone and muscle cells is altered, leading to impaired...

The blood-brain barrier (BBB) is highly specialized to protect the brain from harmful circulating factors in the blood and maintain brain homeostasis^(1,2). The brain endothelial glycocalyx layer, a carbohydrate-rich meshwork composed primarily of proteoglycans, glycoproteins and glycolipids that coats the BBB lumen, is a key structural component of the BBB^(3,4). This layer forms the first interface between the blood and brain vasculature, yet little is known about its composition and roles in...

CONCLUSIONS: Participation in exercise/activities is associated with a lower likelihood of frailty. Regular housework may also contribute to reducing frailty risk.

The dentate gyrus of the hippocampus is important for many cognitive functions, including learning, memory, and mood. Here, we present transcriptome-wide spatial gene expression maps of the human dentate gyrus and investigate age-associated changes across the lifespan. Genes associated with neurogenesis and the extracellular matrix are enriched in infants and decline throughout development and maturation. Following infancy, inhibitory neuron markers increase, and cellular proliferation markers...

Extreme heat is well-documented to adversely affect health and mortality, but its link to biological aging-a precursor of the morbidity and mortality process-remains unclear. This study examines the association between ambient outdoor heat and epigenetic aging in a nationally representative sample of US adults aged 56+ (N = 3686). The number of heat days in neighborhoods is calculated using the heat index, covering time windows from the day of blood collection to 6 years prior. Multilevel...

The senescence process is connected to the characteristics of cellular aging. Understanding their causal network helps develop a framework for creating new treatments to slow down the senescence process. A growing body of research indicates that aging may adversely affect stem cells (SCs). SCs change their capability to differentiate into different cell types and decrease their potential for renewal as they age. Research has indicated that consistent physical exercise offers several health...

Most adults experience age-related cognitive decline. However, "Positive-Agers" exhibit superior cognition compared to their age-matched peers. Distinguishing between those with superior cognitive performance and those with cognitive decline over time could better inform treatment therapies in older adults. We developed an algorithm called Optimal Cognitive Scoring (OptiCS) that accurately differentiates "Positive-Agers" from "Cognitive Decliners." This study draws on a cohort of 5797...

Recent studies emphasize that lipid synthesis, metabolism, and transport are crucial in modulating lipid function, underscoring the significance of lipid localization within the cell, in addition to their chemical structure. Ceramides stand out in this context because of their multifaceted roles in cellular processes. Here, we focus on the role of ceramides in apoptosis, senescence, and autophagy as these processes offer unique and contrasting perspectives on how ceramides function and can be...

Closely related genes typically display common essential functions but also functional diversification, ensuring retention of both genes throughout evolution. The histone lysine acetyltransferases KAT6A (MOZ) and KAT6B (QKF/MORF), sharing identical protein domain structure, are mutually exclusive catalytic subunits of a multiprotein complex. Mutations in either KAT6A or KAT6B result in congenital intellectual disability disorders in human patients. In mice, loss of function of either gene...

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Here we report a conserved transcriptomic signature of reduced fatty acid and lipid metabolism gene expression in a Drosophila model of C9orf72 repeat expansion, the most common genetic cause of amyotrophic lateral sclerosis and frontotemporal dementia (ALS/FTD), and in human postmortem ALS spinal cord. We performed lipidomics on C9 ALS/FTD Drosophila, induced pluripotent stem (iPS) cell neurons and postmortem FTD brain tissue. This revealed a common and specific reduction in phospholipid...

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The experience of human parenthood is near ubiquitous and can profoundly alter one's body, mind, and environment. However, we know very little about the long-term neural effects of parenthood for parents themselves, or the implications of pregnancy and caregiving experience on the aging adult brain. Here, we investigate the link between the number of children parented and age on brain function in 19,964 females and 17,607 males from the UK Biobank. In both females and males, parenthood was...

Cellular senescence gene sets have been leveraged to overcome the inadequate sensitivity or specificity of single markers. However, growing evidence of heterogeneity among tissues in senescent cell phenotypes and gene expression profiles has highlighted the need for tissue-specific gene sets. SenSkin™ was curated by an expert review of literature on cellular senescence in the skin and characterized with pathway analysis. To validate SenSkin™, it was evaluated for enrichment with chronological...

Larger, longer-lived species are expected to have a higher cancer prevalence compared to smaller, shorter-lived species owing to the greater number of cell divisions that occur during their lifespan. Yet, to date, no evidence has been found to support this expectation, and no association has been found between cancer prevalence and body size across species-a phenomenon known as Peto's paradox. Specifically, while anticancer mechanisms have been identified for individual species, wider...

Brain age (BA), distinct from chronological age (CA), can be estimated from MRIs to evaluate neuroanatomic aging in cognitively normal (CN) individuals. BA, however, is a cross-sectional measure that summarizes cumulative neuroanatomic aging since birth. Thus, it conveys poorly recent or contemporaneous aging trends, which can be better quantified by the (temporal) pace P of brain aging. Many approaches to map P, however, rely on quantifying DNA methylation in whole-blood cells, which the...

With the intensification of population aging, the proportion of elderly breast cancer patients is continuously increasing, among which those with low HER2 expression account for approximately 45 %-55 % of all cases within traditional HER2-negative breast cancer. Concurrently, the significant therapeutic effect of T-DXd on patients with HER2-low tumors has brought this group into the public spotlight. Since the clinical approval of T-DXd in 2019, there has been a significant vertical surge in the...

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Impaired glucose uptake in the brain is an early presymptomatic manifestation of Alzheimer's disease (AD), with symptom-free periods of varying duration that likely reflect individual differences in metabolic resilience. We propose a systemic "bioenergetic capacity", the individual ability to maintain energy homeostasis under pathological conditions. Using fasting serum acylcarnitine profiles from the AD Neuroimaging Initiative as a blood-based readout for this capacity, we identified subgroups...