Aging & Longevity

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...

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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.

The accumulation of senescent endothelial cells within the endothelium leads to vascular dysfunction. Independent studies have linked miR-217, a senescence-associated microRNA and FOXO3, a longevity factor, to cellular senescence in different study models. However, their roles and direct interaction in endothelial replicative senescence (RS) remain to be investigated. This study sought to investigate the role of miR-217/FOXO3 axis in endothelial cell senescence. Young and RS HUVEC models were...

Longitudinal studies provide conflicting evidence regarding the impact of vitamin D deficiency on cognitive performance in older individuals. The present study aimed to investigate whether vitamin D deficiency is a risk factor for poorer trajectories in global cognition and specific cognitive domains over a six-year follow-up period. This cohort study analysed data from 2625 participants aged 50 years or older from the English Longitudinal Study of Ageing. Vitamin D [25-hydroxyvitamin D,...

DNA-protein crosslinks (DPCs) are endogenous and chemotherapy-induced genotoxic DNA lesions and, if not repaired, lead to embryonic lethality, neurodegeneration, premature ageing, and cancer. DPCs are heavily polyubiquitinated, and the SPRTN protease and 26S proteasome emerged as two central enzymes for DPC proteolysis. The proteasome recognizes its substrates by their ubiquitination status. How SPRTN protease, an essential enzyme for DPC proteolysis, achieves specificity for DPCs is still not...

Smoking is one of the most recognized risk factors for pulmonary fibrosis (PF). However, the underlying mechanism is not well understood. This study reveals smoking increases the risk of developing idiopathic PF (IPF) and that smoked IPF patients exhibit higher levels of senescence markers than non-smoker IPF patients. Moreover, smoking enhances bleomycin (Bleo)-induced PF, along with obvious senescence of type II alveolar (AT2) cells. RNA-seq assay identifies cigarette downregulates protection...

CONCLUSIONS: This study is the first to establish normative reference values for PhA across the lifespan of a Korean population aged 10-80 years and the cutoff points for diagnosing sarcopenia in older adults.

CONCLUSION: Activities of Daily Living mediates the relationship between social participation and Self-rated Health. Attention should be paid to the Activities of Daily Living of older adults, with particular attention to those living alone and those who are chronically ill, and to social resources to enhance the social participation of older persons.