Aging & Longevity

Previous work showed that natural selection has acted to minimize the genomic frequencies of representative dynamic DNA sequences capable of forming G-quadruplex, Triplex, hairpin, and i-motif structures in long-lived mammals, thus diminishing the mutagenic potential of their genomes. This report extends findings with single sequences to broadly distributed G3-4N1-7G3-4N1-7G3-4N1-7G3-4 dynamic sequence motifs and identifies a second, previously unknown, pool of dynamic DNA sequences that escape...

Obesity-related conditions are among the leading causes of preventable death and are increasing in prevalence worldwide. Body size and composition are complex traits that are challenging to characterize due to environmental and genetic influences, longitudinal variation, heterogeneity between sexes, and differing health risks based on adipose distribution. Here, we construct a 4-factor genomic structural equation model using 18 measures, unveiling shared and distinct genetic architectures...

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The progressive loss of cerebral white matter during aging contributes to cognitive decline, but whether reduced blood flow is a cause or a consequence remains debatable. Using deep multi-photon imaging in mice, we examined microvascular networks perfusing myelinated tissues in cortical layer 6 and the corpus callosum. We identified sparse, wide-reaching venules, termed principal cortical venules, which exclusively drain deep tissues and resemble the vasculature at the human cortex and U-fiber...

Aging is a major risk factor in amyotrophic lateral sclerosis (ALS) and other adult-onset neurodegenerative disorders. Whereas young neurons are capable of buffering disease-causing stresses, mature neurons lose this ability and degenerate over time. We hypothesized that the resilience of young motor neurons could be restored by reexpression of the embryonic motor neuron selector transcription factors ISL1 and LHX3. We found that viral reexpression of ISL1 and LHX3 selectively in postnatal motor...

Cannabidiol (CBD), a non-psychoactive cannabinoid, has been studied for its various health-promoting effects recently. This study investigates the effects of dietary CBD to the circadian clock of Drosophila melanogaster as a model animal and its many physiological effect to flies. We showed that CBD extended the period of locomotor activity in a dose-dependent manner, suggesting its influence on the circadian clock. Additionally, CBD improved sleep quality and extended lifespan under starvation...

CONCLUSIONS: Findings suggest current impairment in vision or motor function may be strong indicators of prevalent dementia in older adults.

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The meninges serve as a critical interface between the peripheral immune system and the central nervous system, playing a crucial role in maintaining parenchymal homeostasis. Neurodegenerative disorders, such as amyloidosis and tauopathies, are marked by the accumulation of extracellular neurotoxic amyloid-β (Aβ) plaques and intracellular tau tangles, respectively, leading to neuronal cell death and cognitive decline. The role of the adaptive immune response in these pathologies remains under...

CONCLUSIONS: Our study highlights the complex relationship between genetic legacies and modern diseases, emphasizing the need for gender-sensitive healthcare strategies that consider the unique connections between female reproductive health and aging.

Aging causes significant changes in gene expression and metabolic function of cells in various organs. Although it is known that liver regeneration is delayed by aging, the effects of aging on changes in gene expression and metabolic functions in liver regeneration need further investigation. In this study, we comprehensively analyzed changes in gene expression and metabolic function by liver regeneration in young and old mice to examine the effects of aging on these changes. During the process...

This study investigates the correlation between polypharmacy and gut microbiota compositional changes in older people who were treated with multidrug therapy, aiming to provide insights into the complex interplay between medication use, gut microbiota, and aging. High-throughput sequencing of the 16S rRNA gene was employed to analyze microbial diversity in older patients with multiple chronic diseases and polypharmacy, and the results were compared with a control group of older people without...

Aging is increasingly understood as a multifactorial process involving mitochondrial dysfunction, epigenetic drift, and chronic inflammation. While many age-related pathologies have been linked to impaired mitophagy and transcriptional deregulation, the upstream mechanisms driving these phenomena remain elusive. Here, a unifying hypothesis is proposed: that the progressive reactivation of human endogenous retroviruses (HERVs), combined with latent viral infections acquired during life, imposes...

The segregation of processes into cortical layers is a convergent feature in animal evolution. However, how changes in the cortical layer architecture interact with sensory system function and dysfunction remains unclear. Here we conducted functional and structural layer-specific in vivo 7T magnetic resonance imaging of the primary somatosensory cortex in two cohorts of healthy younger and older adults. Input layer IV is enlarged and more myelinated in older adults and is associated with...

Cellular senescence is a major contributor to aging-related degenerative diseases, including Alzheimer's disease (AD), but much less is known about the key cell types and pathways driving senescence mechanisms in the brain. We hypothesized that dysregulated cholesterol metabolism is central to cellular senescence in AD. We analyzed single-cell RNA-seq data from the ROSMAP and SEA-AD cohorts to uncover cell type-specific senescence pathologies. In ROSMAP snRNA-seq data (982,384 nuclei from...

INTRODUCTION: The shift toward earlier detection in the Alzheimer's disease (AD) continuum underscores the need for more sensitive cognitive outcome assessments (COAs). Traditional COAs may lack precision in capturing cognitive dysfunction during preclinical stages. The Face-Name Associative Memory Exam (FNAME), a cross-modal task that integrates verbal and non-verbal memory, offers enhanced sensitivity and has shown associations with amyloid-β burden across the AD continuum, even in...

Background: Diabetes mellitus is linked to progressive cognitive decline and motor impairments, especially among the aging population, highlighting the importance of early detection through reliable neuronal biomarkers. Proteins such as neurofilament light chain (NFL), neurogranin (Ng), and visinin-like protein 1 (VILIP-1) have emerged as indicators of neurodegeneration and associated behavioral changes. This study examined the effects of combined endurance and resistance exercise, along with...

CONCLUSIONS AND IMPLICATIONS: Regardless of sexual orientation, receiving care at home was the most preferred option, followed by moving to an assisted living facility. In terms of the type of home care, professional home care and a mix of formal and informal care were the most preferred options. Surprisingly, informal care was preferred by only 53.3% of people. Our results revealed that preferences for care settings (eg, own home, nursing home) and preferences for type of care (eg, informal...

CONCLUSIONS AND IMPLICATIONS: Enhanced CRF and muscle strength could offset the risk of premature health span termination associated with accelerated biological aging. Our findings suggest that biological aging rates should be considered in personalized fitness interventions to optimize health span. Public health strategies should prioritize cardiorespiratory and muscular fitness to mitigate aging-related health risks.

The placebo effect, or the positive effects observed after an inert treatment which result from patients' expectations for the therapy, is well documented in human medicine. However, in veterinary medicine, where owner's expectations serve as a proxy for their pets, it remains underexplored, particularly for elderly dogs with cognitive decline. To address this gap, we examined 21 dogs (mean age: 12.85 years, SD: 1.46) from a placebo group in a randomized controlled trial (RCT) and compared their...