Aging & Longevity

Over the past decade, epigenetic clocks have emerged as powerful machine learning tools, not only to estimate chronological and biological age but also to assess the efficacy of anti-ageing, cellular rejuvenation and disease-preventive interventions. However, many computational and statistical challenges remain that limit our understanding, interpretation and application of epigenetic clocks. Here, we review these computational challenges, focusing on interpretation, cell-type heterogeneity and...

Understanding the lifetime risk of dementia can inform public health planning and improve patient engagement in prevention. Using data from a community-based, prospective cohort study (n = 15,043; 26.9% Black race, 55.1% women and 30.8% with at least one apolipoprotein E4 (APOE ε4) allele), we estimated the lifetime risk of dementia (from age 55 years to 95 years), with mortality treated as a competing event. We applied lifetime risk estimates to US Census projections to evaluate the annual...

Analysis of preclinical lifespan studies often assume that outcome data from co-housed animals are independent. In practice, treatments, such as controlled feeding or putative life-extending compounds, are applied to whole housing units, and as a result, the outcomes are potentially correlated within housing units. We consider intra-class (here, intra-cage) correlation in three published and two unpublished lifespan studies of aged mice encompassing more than 20,000 observations. We show that...

Volcanic provinces are among the most active but least well understood landscapes on Earth. Here, we show that the central Cascade arc, USA, exhibits systematic spatial covariation of topography and hydrology that are linked to aging volcanic bedrock, suggesting systematic controls on landscape evolution. At the Cascade crest, a locus of Quaternary volcanism, water circulates deeply through the upper [Formula: see text]1 km of crust but transitions to shallow and dominantly horizontal flow as...

Aging is a complex process characterized by biological decline and a wide range of molecular alterations to cells, including changes to DNA methylation. In this study, we used a male-specific epigenetic marker of aging to build an epigenetic predictor that measures long-term androgen exposure in sheep and mice (median absolute error of 4.3 and 1.4 mo, respectively). We term this predictor the androgen clock and show its "tick" is mediated by the androgen receptor and can be accelerated beyond...

Cellular senescence is a complex biological response to sublethal damage. The RNA-binding protein HNRNPK was previously found to decrease prominently during senescence in human diploid fibroblasts. Here, analysis of the mechanisms leading to reduced HNRNPK abundance revealed that in cells undergoing senescence, HNRNPK mRNA levels declined transcriptionally and full-length HNRNPK protein was progressively lost, while the abundance of a truncated HNRNPK increased. The ensuing loss of full-length...

A combination of intermittent fasting and administering Wnt3a proteins to a bone injury can rejuvenate bone repair in aged mice.

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CONCLUSION: This study found that nine circulating metabolites and their ratios with significant causal associations to aSAH, while no metabolites and their ratios were causally linked to IAs. These results suggest possible mechanisms and predictive molecular targets for IAs and aSAH.

People living with HIV are at higher risk of heart failure and associated left atrial remodeling compared to people without HIV. Mechanisms are unclear but have been linked to inflammation and premature aging. Here we obtain plasma proteomics concurrently with cardiac magnetic resonance imaging in two independent study populations to identify parallels between HIV-related and aging-related immune dysfunction that could contribute to atrial remodeling and clinical heart failure. We discover a...

An emerging biomarker of blood-brain barrier (BBB) permeability is the time of exchange (Tex) of water from the blood to tissue, as measured by multi-echo arterial spin labeling (ASL) MRI. This new non-invasive sequence, already tested in mice, has recently been adapted to humans and optimized for clinical scanning time. In this study, we studied the normal variability of Tex over age and sex, which needs to be established as a reference for studying changes in neurological disease. We evaluated...

Alzheimer's disease (AD) is a progressive neurodegenerative disorder in which there is slow and gradual impairment of mental function. Considering the increase in cases due to population aging, the potential benefits of physical training in AD are of great importance and need further elucidation. This study aims to identify the impact of physical training on crucial aspects of AD such as cognitive status, physical performances, quality of life and activities of daily living. The bibliographic...

CONCLUSION: This cross-sectional study reveals significant correlations between sleep quality and key factors such as physiological status, community participation, and daily functional activities in older adults with dynapenia. These findings underscore the importance of addressing these determinants to enhance sleep quality in this population.

CONCLUSIONS: Nearly 8%, or an estimated 1 million community-ambulating U.S. older adults, had severe impairments in peak expiratory flow in 2015; these older adults have a substantially higher risk of losing the ability to ambulate community distances over the subsequent year.

CONCLUSION: Under typical United States practice, cataract surgery for older patients was not significantly associated with cognitive improvement or decline in the year after, compared with the year before, surgery.

Age-related cognitive impairment and dementia pose a significant global health, social, and economic challenge. While Alzheimer's disease (AD) has historically been viewed as the leading cause of dementia, recent evidence reveals the considerable impact of vascular cognitive impairment and dementia (VCID), which now accounts for nearly half of all dementia cases. The Mediterranean diet-characterized by high consumption of fruits, vegetables, whole grains, fish, and olive oil-has been widely...

Rheumatoid arthritis (RA) is an age-related chronic inflammatory disease which may include accelerated biological ageing processes in its pathogenesis. To determine if increased biological age is associated with risk of RA and/or is present once disease is established. We used DNA methylation to compare biological age (epigenetic age) of immune cells in adults at risk of RA and those with confirmed RA, including twins discordant for RA. The established RA studies were secondary analyses of...

Gut microbiota plays a crucial role in the host health in the aging process. However, the mechanisms for how gut microbiota triggers cellular senescence and the consequent impact on human aging remain enigmatic. Here we show that phenylacetylglutamine (PAGln), a metabolite linked to gut microbiota, drives host cellular senescence. Our findings indicate that the gut microbiota alters with age, which leads to increased production of phenylacetic acid (PAA) and its downstream metabolite PAGln in...

CONCLUSION: The findings of this study underscore the necessity of policies and institutional measures grounded in community networks to mitigate the risk of all-cause mortality among vulnerable groups with persistently poor HLST.

Coronavirus disease 2019 (COVID-19) poses significant risks for solid organ transplant recipients, who have atypical but poorly characterized immune responses to infection. We aim to understand the host immunologic and microbial features of COVID-19 in transplant recipients by leveraging a prospective multicenter cohort of 86 transplant recipients age- and sex-matched with 172 non-transplant controls. We find that transplant recipients have higher nasal SARS-CoV-2 viral abundance and impaired...