Aging & Longevity

Immune aging is associated with decreased vaccine responses, but biomarkers for vaccine responsiveness remain unidentified. We analyzed immunotypes describing pre-vaccination immune cell profiles and their associations with triple vaccine responsiveness to influenza, pneumococcal, and SARS-CoV-2 vaccines in adults aged 25-78 years. Additionally, we developed an innovative measure, immune entropy, to quantify cumulative perturbations in the immune cell subset network. Specific immunotypes were...

An increasing number of physically active adults are taking the mTOR inhibitor rapamycin off label with the goal of extending healthspan. However, frequent rapamycin dosing disrupts metabolic health during sedentary conditions and abates the anabolic response to exercise. Intermittent once-weekly rapamycin dosing minimizes many negative metabolic side effects of frequent rapamycin in sedentary mice. However, it remains unknown how different rapamycin dosing schedules impact metabolic, physical,...

Micro/nanoplastics (MNPs), pervasive environmental pollutants, accumulate in cardiovascular tissues and drive premature aging through multiscale pathophysiological cascades. This review synthesizes evidence establishing environmental phenotypic aging as a novel mechanistic link between MNP exposure and cardiovascular senescence. MNPs induce mitochondrial damage involving cristae disruption and mtDNA leakage activating cGAS-STING, epigenetic reprogramming encompassing METTL3-mediated m6A...

Our brain is bathed in cerebrospinal fluid (CSF) that is produced by the choroid plexus. CSF serves as a dispersion route for hormones and nutrients, and a conduit for waste clearance. Age-dependent reduction in the CSF secretion rate could influence cerebral waste clearance and thereby promote cognitive deficits in the elderly. Here, we resolve age-dependent modulation of CSF dynamics and choroid plexus function by complementary in vivo determinations of intracranial pressure (ICP) and CSF...

Nipah virus (NiV) causes a severe neurological disease in humans. The first NiV outbreak, in Malaysia, involved pig-to-human transmission, that resulted in significant economic losses to the local pig industry. Despite the risk NiV poses to pig-dense regions, no licensed vaccines exist. This study therefore assessed three NiV vaccine candidates in pigs: (1) adjuvanted soluble NiV (s)G protein, (2) adjuvanted pre-fusion stabilised NiV (mcs)F protein, and (3) adenoviral vectored NiV G (ChAdOx1 NiV...

Gut microbiota (GM) is implicated in aging biology, yet its dual regulatory role in the distinct yet interconnected processes of lifespan extension and aging remains poorly understood. This study employed genetic approaches to identify GM taxa exerting causal effects on longevity and aging and assess the mediation role of cerebrospinal fluid (CSF) proteins. We leveraged summary statistics of the GM taxa (207 taxa, 7738 participants from the Dutch Microbiome Project), the CSF proteins (7008...

Accurate and convenient assessment of individual aging is crucial for identifying health risks and preventing aging-related diseases. Nonetheless, current aging proxies often face challenges such as methodological limitations, weak associations with adverse outcomes and limited generalizability. Here we propose a framework that leverages large language models (LLMs) to estimate individual overall and organ-specific aging using only health examination reports. We validated this approach across...

Multiple sclerosis (MS) typically presents in early to middle adulthood, but owing to advancements in health care, many individuals with MS now live a normal lifespan, and approximately half of the people currently living with MS are ≥50 years of age. As people living with MS age, their diagnosis, treatment and disease management become more complex owing to the effects of ageing, immunosenescence and comorbidities. Furthermore, diagnosis of late-onset MS (onset above 50 years of age) often...

CONCLUSIONS: Medical therapies aim at restoring a balanced bone turnover and preventing bone tissue loss could be indicated in HypoPT cases with reduced bone mass to grant a better bone health at any age.

CONCLUSION: Our findings suggest that RSV is an important determinant of serious post-discharge cardiovascular outcomes in older adults. Further, they underline the importance of vaccination in this population, regardless of pre-existing risk factors.

From understanding others' mental states to interpreting social cues, aging impairs social abilities. These impairments might not seem surprising given they rely on other cognitive functions such as memory, attention and decision-making, which are known to decline with age. It is, however, unclear to what degree impairments of more basic perceptual abilities, such as eye-gaze detection, contribute to or even precede the decline in social skills. Previous studies have obtained mixed results when...

INTRODUCTION: Older age is associated with alterations in executive functioning (EF). Age-related alterations in the integrity of structural brain networks may contribute to EF decline, with potential consequences for independent living. Graph theory provides powerful metrics to examine the brain's structural connectome, but few studies have investigated the relationship of EF and structural brain networks, as described by graph-theoretical measures, in older adults. We aimed to investigate the...

CONCLUSION: Peer programs have continued to leverage hybrid communication and expanded health and city partnerships to meet the needs of socially isolated older adults. Results further suggest their potential to be integrated into future public health emergency responses.

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...