Aging & Longevity
DNA methylation-based age prediction and sex-specific epigenetic aging in a lizard with female-biased longevity
Sex differences in life span are widespread across animal taxa, but their causes remain unresolved. Alterations to the epigenome are hypothesized to contribute to vertebrate aging, and DNA methylation-based aging clocks allow for quantitative estimation of biological aging trajectories. Here, we investigate the influence of age, sex, and their interaction on genome-wide DNA methylation patterns in the brown anole (Anolis sagrei), a lizard with pronounced female-biased survival and longevity. We...
Monoaminergic neurotransmitters are bimodal effectors of tau aggregation
Neurotransmitters (NTs) mediate trans-synaptic signaling, and disturbances in their levels are linked to aging and brain disorders. Here, we ascribe an additional function for NTs in mediating intracellular protein aggregation by interaction with cytosolic protein fibrils. Cell-based seeding experiments revealed monoaminergic NTs as inhibitors of tau. Seeding is a disease-relevant mechanism involving catalysis by fibrils, leading to the aggregation of proteins in Alzheimer's disease and other...
CAV1 Exacerbates Renal Tubular Epithelial Cell Senescence by Suppressing CaMKK2/AMPK-Mediated Autophagy
Renal proximal tubular epithelial cell (PTEC) senescence and defective autophagy contribute to kidney aging, but the mechanisms remain unclear. Caveolin-1 (CAV1), a crucial component of cell membrane caveolae, regulates autophagy and is associated with cellular senescence. However, its specific role in kidney aging is poorly understood. In this study, we generated Cav1 gene knockout mice and induced kidney aging using D-galactose (D-gal). The results showed that CAV1 expression increased in the...
Prevalence and Determinants of Sarcopenia Among Older Adults in India: Insights From the Longitudinal Aging Study in India
CONCLUSION: This study reveals significant associations between sarcopenia and various sociodemographic factors, comorbidities, and geriatric syndromes in older adults in India, suggesting potential areas for targeted intervention. However, further longitudinal studies are needed to validate these findings and clarify the causal relationships of the observed associations.
A novel framework to build saliva-based DNA methylation biomarkers: Quantifying systemic chronic inflammation as a case study
Accessible and non-invasive biomarkers that measure human ageing processes and the risk of developing age-related disease are paramount in preventative healthcare. Here, we describe a novel framework to train saliva-based DNA methylation (DNAm) biomarkers that are reproducible and biologically interpretable. By leveraging a reliability dataset with replicates across tissues, we demonstrate that it is possible to transfer knowledge from blood DNAm to saliva DNAm data using DNAm proxies of blood...
Stochasticity in dietary restriction-mediated lifespan outcomes in Drosophila
Dietary restriction (DR) is widely considered to be one of the most potent approaches to extend healthy lifespan across various species, yet it has become increasingly apparent that DR-mediated longevity is influenced by biological and non-biological factors. We propose that current priorities in the field should include understanding the relative contributions of these factors to elucidate the mechanisms underlying the beneficial effects of DR. Our work conducted in two laboratories represents...
Better objective sleep quality is associated with higher gut microbiota richness in older adults
Aging is associated with disrupted sleep patterns, such as fragmented sleep and reduced efficiency, leading to negative health outcomes. There is evidence of a bidirectional relationship between sleep and gut microbiota, which plays a key role in the gut-brain axis and overall health. However, studies on this relationship in older adults have limited generalizability and show conflicting results, highlighting the need for further research. This study aimed to investigate the associations between...
Nocturia as a clinical marker of loss of function and resilience or risk factor for frailty in older adults? Results of the Berlin Aging Study II
The current study examined cross-sectional and longitudinal associations between nocturia and frailty in a cohort of men and women aged 60 years and older, as evidence on this topic was lacking. We analyzed baseline and follow-up data (n = 1671) from the Berlin Aging Study II (BASE-II), a prospective longitudinal cohort study focusing on the factors associated with "healthy" vs. "unhealthy" aging. Self-reported nocturia was dichotomized into < / ≥ 2 micturitions per night, and frailty was...
Combining non-invasive brain stimulation techniques and EEG markers analysis: an innovative approach to cognitive health in aging
In an era marked by a rapidly aging global population, delving into the intricate neurophysiological changes that accompany the aging process assumes paramount importance. This narrative review offers a comprehensive exploration of the intricate relationship between electromagnetic neuromodulation and electroencephalography (EEG) within the context of aging. Moreover, it showed the promising landscape of non-invasive neuromodulation techniques, encompassing established methodologies like...
Endothelial Colony-Forming Cells (ECFCs) in cerebrovascular aging: Focus on the pathogenesis of Vascular Cognitive Impairment and Dementia (VCID), and treatment prospects
Endothelial colony-forming cells (ECFCs), a unique endothelial progenitor subset, are essential for vascular integrity and repair, providing significant regenerative potential. Recent studies highlight their role in cerebrovascular aging, particularly in the pathogenesis of vascular cognitive impairment and dementia (VCID). Aging disrupts ECFC functionality through mechanisms such as oxidative stress, chronic inflammation, and cellular senescence, leading to compromised vascular repair and...
Comparative phenotyping of C57BL/6J substrains reveals distinctive patterns of cardiac aging
Research in aging often refers to animal models, particularly C57BL/6J (B6J) mice, considered gold standard. However, B6J mice are distributed by different suppliers, which results in divers substrains exhibiting notable phenotypic differences. To ensure a suitable phenotype of cardiac aging, we performed heart analyses of young (5 months) and old B6J mice (24 months) from two substrains: B6JRj (Janvier) and B6JCrl mice (Charles River). In hearts of both substrains, myocardial fibrosis increased...
Role for neurological and immunological resilience in the pathway of the aging muscle powerpenia: InCHIANTI study longitudinal results
The neuromuscular junction shows several degenerative changes with aging, resulting in a reduction of transmission efficacy. These changes, paired with low-grade chronic inflammation, were considered triggers of the aging muscle processes. The main objective of this study is to assess the role of leukocyte count-derived ratios, nerve conduction velocity (NCV), and compound muscle action potential (CMAP) in determining time-dependent reduction in lower limb muscle explosive strength, a condition...
An mTOR inhibitor discovery system using drug-sensitized yeast
Inhibition of the target of rapamycin (TOR/mTOR) protein kinase by the drug rapamycin extends lifespan and health span across diverse species. However, rapamycin has potential off-target and side effects that warrant the discovery of additional TOR inhibitors. TOR was initially discovered in Saccharomyces cerevisiae (yeast) which contains two TOR paralogs, TOR1 and TOR2. Yeast lacking functional Tor1 are viable but are hypersensitive to growth inhibition by TORC1 inhibitors, which is a property...
SLC29A1 and SLC29A2 are human nicotinamide cell membrane transporters
Nicotinamide (NAM), a main precursor of NAD+, is essential for cellular fuel respiration, energy production, and other cellular processes. Transporters for other precursors of NAD+ such as nicotinic acid and nicotinamide mononucleotide (NMN) have been identified, but the cellular transporter of nicotinamide has not been elucidated. Here, we demonstrate that equilibrative nucleoside transporter 1 and 2 (ENT1 and 2, encoded by SLC29A1 and 2) drive cellular nicotinamide uptake and establish...
Oligodendrocyte precursor cells facilitate neuronal lysosome release
Oligodendrocyte precursor cells (OPCs) shape brain function through many non-canonical regulatory mechanisms beyond myelination. Here we show that OPCs form contacts with their processes on neuronal somata in a neuronal activity-dependent manner. These contacts facilitate exocytosis of neuronal lysosomes. A reduction in the number or branching of OPCs reduces these contacts, which is associated with lysosome accumulation and altered metabolism in neurons and more senescent neurons with age. A...
Author Correction: In vivo base editing extends lifespan of a humanized mouse model of prion disease
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Indoor ventilation frequency and cognitive function among Chinese old adults: the multiple mediation effect of anxiety and self-rated health
CONCLUSIONS: Studies have shown that indoor ventilation frequency can improve cognitive function by reducing anxiety and improving self-rated health in older people Chinese. Encouraging older adults to increase the frequency of indoor ventilation will benefit their mental health and cognitive function.
"Loneliness is a sad disease": oldest old adults' empirical definition of loneliness and social isolation from a mixed-method study in Northern Italy
CONCLUSION: The knowledge of the meanings that oldest old give to the two concepts may inspire advanced intervention aimed at buffering the psychological and social consequences of loneliness and social isolation in the older population.
Establishment and application of a zebrafish model of Werner syndrome identifies sapanisertib as a potential antiaging drug
Aging is a complex process that affects multiple organs, and the discovery of a pharmacological approach to ameliorate aging is considered the Holy Grail of medicine. Here, we performed an N-ethyl-N-nitrosourea forward genetic screening in zebrafish and identified an accelerated aging mutant named meteor (met), harboring a mutation in the Werner syndrome RecQ-like helicase (wrn) gene. Loss of wrn leads to a short lifespan and age-related characteristics in the intestine of zebrafish embryos,...
SIV monoclonal antibody administration spanning treatment interruption in macaques delays viral rebound and selects escape variants
HIV-1 envelope broadly neutralizing antibodies represent a promising component of HIV-1 cure strategies. To evaluate the therapeutic efficacy of combination monoclonal antibodies (mAbs) in a rigorous nonhuman primate model, we tested different combinations of simian immunodeficiency virus (SIV) neutralizing mAbs in SIVmac251-infected rhesus macaques. Antiretroviral therapy-suppressed animals received anti-SIV mAbs targeting multiple Env epitopes spanning analytical treatment interruption (ATI)...
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