Aging & Longevity

DNA methylation (DNAm) algorithms have been developed to assess biological aging and its association with cancer. Despite their potential, direct comparisons to identify the most accurate algorithm for predicting cancer risk and mortality remain limited. The study population (n = 2532) consisted of adults aged 50 years and older from the National Health and Nutrition Examination Survey, with 17-year follow-up mortality data. Twelve DNAm algorithms were evaluated using Illumina EPIC BeadChip...

This study is the first to investigate the anti-aging effects of the newly synthesized compound, 3,4,5-tri-feruloylquinic acid (TFQA), in vivo using the senescence-accelerated mouse prone 8 (SAMP8) model, through integrated whole-transcriptomic and biochemical analyses. Oral administration of TFQA (1 mg/kg body weight) for 37 days led to significant cognitive improvements, as demonstrated by enhanced performance in the Morris water maze (MWM) test, including reduced escape latency and increased...

The effects of environmental stress on animal life are gaining importance with climate change. Diapause is a dormancy program that occurs in response to an adverse environment, followed by resumption of development and reproduction upon the return of favorable conditions. Diapause is a complex trait, so we leveraged the Drosophila Genetic Reference Panel (DGRP) lines and conducted a genome-wide association study (GWAS) to characterize the genetic basis of diapause. We assessed post-diapause and...

One of the most promising interventional targets for brain health is cerebral perfusion, but its link to white matter (WM) aging remains unclear. Motivated by existing literature demonstrating links between declining cortical perfusion and the development of WM hyperintensities, we posit that regional WM hypoperfusion precedes deteriorating WM integrity. Using the Human Connectome Project Aging (HCP-A) data set, we examine tract-wise associations between WM microstructural integrity (i.e....

Central memory CD8^(+) T cells (T(cm)) represent the prominent memory T cell subset in human blood, yet the persistence of T cell receptor (TCR) clonotypic and transcriptional features of epitope-specific T(cm) pools across the human lifespan remains unknown. We analyzed T(cm) CD8^(+) T cells specific for HLA-A*02:01-M1(58-66) (A2/M1(58); a prominent influenza epitope) in newborns, children, adults, and older adults directly ex vivo. Our data provide evidence that epitope-specific T(cm) CD8^(+)...

Alternating hemiplegia of childhood (AHC) is a neurodevelopmental disorder with no disease-modifying treatment. Mutations in ATP1A3, encoding an Na^(+)/K^(+) ATPase subunit, cause 70% of AHC cases. Here, we present prime editing (PE) and base editing (BE) strategies to correct ATP1A3 and Atp1a3 mutations in human cells and in two AHC mouse models. We used PE and BE to correct five prevalent ATP1A3 mutations with 43%-90% efficiency. AAV9-mediated in vivo PE corrects Atp1a3 D801N and E815K in the...

The impact of SARS-CoV-2 and the COVID-19 pandemic on brain health is recognised, yet specific effects remain understudied. We investigate the pandemic's impact on brain ageing using longitudinal neuroimaging data from the UK Biobank. Brain age prediction models are trained from hundreds of multi-modal imaging features using a cohort of 15,334 healthy participants. These models are then applied to an independent cohort of 996 healthy participants with two magnetic resonance imaging scans: either...

Improving gut health by altering the activity of intestinal stem cells is thought to have the potential to reverse aging. The aged Drosophila midgut undergoes hyperplasia and barrier dysfunction. However, it is still unclear how to limit hyperplasia to extend lifespan. Here, we show that early midgut injury prevents the abrupt onset of aging hyperplasia and extends lifespan in flies. Daily transcriptome profiling and lineage tracing analysis show that the abrupt onset of aging hyperplasia is due...

Microglia are implicated in aging, neurodegeneration and Alzheimer's disease (AD). Low-plex protein imaging does not capture cellular states and interactions in the human brain, which differs from rodent models. Here we used multiplexed ion beam imaging to spatially map cellular states and niches in cognitively normal human brains, identifying a spectrum of proteomic microglial profiles. Defined by immune activation states that were skewed across brain regions and compartmentalized according to...

Early detection of amnestic mild cognitive impairment (aMCI) is crucial for timely interventions. This study combines scalp recordings of lateralized auditory, visual, and somatosensory stimuli with a flexible and interpretable support vector machine learning pipeline to differentiate individuals diagnosed with aMCI from healthy controls. Event-related potentials (ERPs) and functional connectivity (FC) matrices from each modality successfully predicted aMCI. Reduced ERP amplitude in aMCI...

No abstract

No abstract

We recently showed that the next-generation epigenetic aging clock CheekAge was significantly associated with 33 different health and disease signals across 25 publicly available MethylationEPIC datasets. We additionally uncovered DNA methylation sites that played a disproportionately important role in driving the ability of CheekAge to associate with each of these variables. We dubbed these "pro" CpGs because of their ability to promote a given association. Here, we identify 2639 common DNA...

CONCLUSIONS AND IMPLICATIONS: Health promotion interventions can improve clinical outcome indicators for prefrail older adults and possess potential advantages in terms of cost-effectiveness. However, the benefits largely depend on the type and duration of the intervention. When assessing these factors together, home-based health promotion interventions seem to be a particularly beneficial strategy, offering both cost efficiency and meaningful improvements in prefrailty status.

The DNA-dependent protease SPRTN maintains genome stability by degrading toxic DNA-protein crosslinks (DPCs). To understand how SPRTN's promiscuous protease activity is confined to cleavage of crosslinked proteins, we reconstitute the repair of DPCs including their modification with SUMO and ubiquitin chains in vitro. We discover that DPC ubiquitylation strongly activates SPRTN independently of SPRTN's known ubiquitin-binding domains. Using protein structure prediction, MD simulations and NMR...

As a cardinal marker of brain ageing, lifetime brain atrophy obtained from a cross-sectional magnetic resonance image promises to boost statistical power to uncover novel genetic mechanisms of neurodegeneration. By analysing five young and old adult cohorts, we perform the most definitive study on lifetime brain atrophy's measurement and correlates. It is simply calculated from the relationship between total brain volume and intracranial volume, using the difference, ratio, or...

Physical activity (PA) is one of the most fundamental traits in the animal kingdom, has pervasive health benefits, and is genetically influenced. Using data from the Million Veteran Program, we conducted genetic analyses of leisure, work and home-time PA. For leisure, we included 189,812 individuals of European ancestry (SNP-based heritability (h²) = 0.083 ± 0.005), 27,044 of African ancestry (h² = 0.034 ± 0.017) and 10,263 of Latin American ancestry (h² = 0.083 ± 0.036) in a cross-ancestry...

With concerns about aging dams and nonstationary changes in hydrologic extremes (e.g., flooding), questions arise about whether existing dams may be at risk of failure and pose threats to society. Here, we analyzed 33 dams across the United States to investigate temporal trends in dam overtopping probabilities of annual maximum dam water levels. These dams were selected because of the availability of public domain long-term time series of uncontrolled water levels (50 years or longer). We...

The choroid plexus (ChP) is a complex ventricular structure that forms a semi-permeable barrier between the blood and cerebrospinal fluid (CSF). It is responsible for CSF secretion and clearance, contains macrophages, and is one of the few sites within the central nervous system (CNS) where T cells are present. Additionally, the ChP plays a role in detecting peripheral inflammation, which leads to the modulation of its epithelial cell function. Despite its critical importance in maintaining...

CONCLUSIONS: This study reveals that LST and MVPA may play a causal role in the process of aging. Accordingly, public health efforts to promote increased physical activity and reduce sedentary time can effectively combat accelerated aging.