Aging & Longevity

Early-life nutrition can exert long-lasting effects on later-life health. Given that lactose is extensively consumed during early mammalian development, this raises the intriguing possibility that lactose or its constituent galactose may exert beneficial nutritional programming effects. We tested here whether early-life (larval period) co-consumption of galactose and glucose (GALGLU; as in hydrolysed lactose) shapes later-life (adult) lifespan in Drosophila melanogaster. Larval GALGLU versus...

Epigenetic clocks are commonly used aging biomarkers based on DNA methylation that predict long-term morbidity and mortality risk. Increased cellular senescence with age is also posited to contribute to age-related disease and mortality. However, prior studies have found that existing epigenetic clocks show inconsistent associations with cellular senescence and no reductions after senolytic treatment. We hypothesize this reflects that senescence-related CpGs are a small proportion of age-related...

Ageing is a progressive biological process causing a reduction in tissue and cellular function due to accumulated molecular damage over time. Cellular senescence is a stable cellular state characterized by irreversible cell-cycle arrest accompanied by distinct molecular, epigenetic, and secretory alterations. Moreover, neuroendocrine signalling and epigenetic regulation have had a great impact on controlling ageing and senescence. As a part of the neuroendocrine system, the...

CONCLUSION: These findings highlight the importance of early prevention strategies to address polypharmacy, muscle loss, and low education, all of which are potentially modifiable risk factors. Poorer physical performance was linked to polypharmacy, low muscle mass, and lower educational levels, suggesting a need for additional research into these contributing risk factors.

To investigate organism-wide cellular alterations and epigenomic dynamics during aging, we constructed a single-cell chromatin accessibility atlas spanning 21 mouse tissues across three age groups and both sexes. We found that around one-quarter of 536 organ-specific cell types and 1828 finer-grained subtypes exhibited considerable age-related population shifts. Cellular states from broadly distributed lineages displayed synchronized dynamics with age, indicating systemic signals that coordinate...

Age-related chromatin remodeling includes shared and specific signatures across cell types, sex, and organs.

CONCLUSIONS: Despite limited guidance on methods and biomarkers, this scoping review supports MRS as a promising tool for monitoring exercise-induced metabolic changes in muscle and brain of older adults. However, standardized methodologies and larger number of studies are required to determine which metabolites reliably reflect exercise benefits in aging brain and muscle.

Pancreatic cancer is a highly aggressive tumor with a poor prognosis. The ubiquitin-proteasome system is crucial in maintaining protein homeostasis and regulating cellular senescence, thereby influencing tumorigenesis and progression; however, the specific mechanisms underlying this process remain unclear. Ubiquitin protein ligase E3A (UBE3A) is associated with various tumors; however, its potential role in pancreatic cancer warrants further investigation. The effects of UBE3A on cellular...

The self-renewal capacity of intestinal stem cells (ISCs) declines with aging, leading to a loss of homeostasis and an increased susceptibility to intestinal diseases. Despite the established significance of lipid metabolism and epigenetic regulation in ISC function, the molecular mechanisms that connect these processes to aging-related ISC dysfunction remain elusive. Here, we hypothesize that histone 3 lysine 36 trimethylation (H3K36me3) might act as a bridge between these processes. In this...

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CONCLUSIONS: We present a real-life baseline study on centenarians. Our findings contribute to understanding extreme longevity and may facilitate future studies, progress in healthcare, lifestyle decisions, and societal policies that benefit long-lived people.

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Vitamins are essential metabolites that must be obtained from external sources. In modern times, they have become widely available, leading to their ad hoc consumption. We developed a nutritional genomics framework to systematically identify monogenic diseases responsive to micronutrient modulation. Genome-wide CRISPR screens under varying vitamin B2 and B3 levels revealed dozens of candidate disease genes amenable to rescue by individual vitamins. In the vitamin B3 screen, NAD(P)HX dehydratase...

Frailty, a syndrome that decreases healthspan in older individuals, lacks effective therapies. We conducted a randomized, dose-finding clinical trial to test whether human bone marrow-derived allogeneic mesenchymal stem cells (MSCs; laromestrocel) improve physical functioning and patient self-reported outcomes in ambulatory individuals with frailty (ClinicalTrials.gov #NCT03169231; N = 148). Laromestrocel infusion results in clinically meaningful, dose- and time-dependent increases in the 6-min...

The physiological effects of spaceflight resemble those of ageing and prolonged inactivity, and ground-based microgravity analogs have emerged as promising models for studying frailty. The human microbiome is increasingly recognised for its role in age-associated decline, although precise mechanisms remain unclear. Here, we evaluate the gut and oral microbiomes of twenty-two participants, aged 55-65, who were enrolled in a head-down tilt bedrest (HDBR) study, the first Canadian HDBR study...

Programmed cell death-1 (PD-1) is a co-inhibitory receptor expressed on T cells that dampens TCR and CD28 signaling in the immunological synapse. PD-1 is significantly upregulated on T cells in the tumor microenvironment, where it promotes exhaustion in the context of chronic antigen restimulation. Exhaustion renders T cells hyporesponsive and ineffectual, but potentially resistant to restimulation-induced cell death (RICD). Restimulation-induced cell death (RICD) is a critical propriocidal...

Systemic inflammation ("inflammaging") accelerates biological aging and drives cardiovascular, metabolic, and neurodegenerative disease. Circadian rhythms regulate the amplitude and timing of immune responses, yet their mechanistic role in inflammation and longevity remains unexplored. In 62,000 adults with 7-day wearable accelerometry, interpretable machine learning model identified rhythm amplitude, stability, and moderate-to-vigorous physical activity (MVPA) as dominant predictors of...

Simple performance-based tests such as gait speed, the Five-Times-Sit-to-Stand Test (FTSST), balance tests, and handgrip strength are associated with health outcomes. We aimed to establish age- and sex-specific reference (normative) values for these tests in the English population. Adults aged ≥ 50 years (female n = 4,234; male n = 3,424) from the English Longitudinal Study of Ageing were included. Weighted percentiles ranging from the 5th to the 95th percentile [P5-95] were calculated. Best...

Exercise, a well-recognized non-pharmacological anti-aging strategy, is key for human health. Growing evidence points to exhaustive or strenuous exercise, especially when recovery is inadequate, may trigger oxidative damage and accelerate aging. This study aims to systematically the effects of exhaustive and/or strenuous exercise on aging-related molecular and physiological biomarkers using a systematic review and meta-analysis. A systematic literature search was conducted across PubMed,...

Intrinsic capacity (IC), a composite measure of physical and mental capacities, reflects the functional manifestations of biological aging, yet large-scale population evidence on how IC varies throughout adulthood outside Western settings remains limited. Using data from 17,086 Chinese adults aged 25-89 years in the nationally representative PENG ZU cohort, we characterized age-related variation in IC and its associated factors. IC was assessed across five domains (locomotion, cognition,...