Aging & Longevity

Cellular senescence is a complex biological process with a dual role in tissue homeostasis and aging-related pathologies. Accumulation of senescent cells promotes chronic inflammation, tissue dysfunction, age-related diseases, and tumor suppression. Recent advancements in immunotherapy have positioned T cell-based approaches as precision tools for the targeted clearance of senescent cells, offering a novel avenue for anti-aging interventions. This review explores the molecular mechanisms...

Acetylcholine (ACh) secreted by the non-neuronal cholinergic system (NNCS), an intrinsic system found in the mammalian heart, is not dependent on neuronal inputs for its synthesis. Accumulating evidence demonstrates that ACh exerts multifaceted cardioprotective effects through the NNCS. Under extreme stress or demand, ACh slows heart rate by modulating cardiac chronotropy. Simultaneously, it protects the myocardium from ischemic, hypoxic, and other stressors. Beyond its direct effects on the...

With age, bones mechanosensitivity is reduced, which limits their ability to adapt to loading. The exact mechanism leading to this loss of mechanosensitvity is still unclear, making developing effective treatment challenging. Current treatments mostly focus on preventing bone mass loss (such as bisphosphonates) or promoting bone formation (such as Sclerostin inhibitors) to limit the decline of bones mass. However, treatments do not target the cause of bone mass loss which may be, in part, due to...

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During aging, hematopoietic stem cell (HSC) function progressively declines which can lead to reduced blood cell production and regeneration. This work uncovered that cell surface presentation of P-selectin (CD62P, encoded by Selp) increases in a large fraction of aging HSCs driven by a proinflammatory milieu in mice. Notably, expression of P-selectin molecularly and functionally dichotomized the aging HSC pool; stem cells presenting with highly abundant P-selectin were hallmarked by...

Longitudinal studies offer a unique opportunity to characterize individual human lifespan trajectories. While challenging, their added value can advance our understanding of neurodevelopment and mental health disorders, with the aim to optimize brain health and mental health.

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Frailty is an age-related geriatric syndrome. We performed a longitudinal study of aging female (n = 40) and male (n = 47) C57BL/6NIA mice, measured frailty index and derived metabolomics data from plasma. We identify age-related differentially abundant metabolites, determine frailty-related metabolites, and generate frailty features, both in the whole cohort and sex-stratified subgroups. Using the features, we perform an association study and build a metabolomics-based frailty clock. We find...

Recent research underscores the crucial role of hormone regulation in benign prostatic hyperplasia (BPH) and the therapeutic promise of growth hormone-releasing hormone (GH-RH) antagonists. BPH incidence in aging men doubled over three decades, driven by prostatic enlargement and lower urinary tract symptoms (LUTS). Aging-related changes in GH-RH and luteinizing hormone-releasing hormone (LH-RH) biology promote BPH through hormonal and inflammatory processes. Traditional therapies provide...

We show that T cells in survivors of childhood leukemia exhibit distinct profiles dominated by aging-associated changes and consistent with premature immune aging. Immune profiles during survivorship in biospecimens (n = 251) from uniformly-treated children with B-acute lymphoblastic leukemia recapitulate heterogeneity at diagnosis in individual patients and correlate with genetic-risk subtypes. These data suggest that pre-therapy immune aging may determine variance in immune status during...

Sensory impairments are common with aging, but studies examining the relationships of these impairments with DNA methylation-based biomarkers of aging, strong predictors of morbidity and mortality, remain sparse. We investigated whether subjective measures of sensory impairment are associated with epigenetic age biomarkers. We conducted a cross-sectional analysis in a representative sample of 2344 U.S. adults from the 1999-2000 and 2001-2002 cycles of the National Health and Nutrition...

The aim of this study is to explore the differences in cortical activation and gait performance during turning walking under cognitive dual-task conditions between young and older adults during cognitive-turning dual task walking, as well as variations in brain functional connectivity in this context. Seventeen young adults and seventeen older adults were included in the study. All participants completed two tasks: a figure-eight turning walk (single-task, ST) and a figure-eight turning walking...

Despite not proliferating, senescent cells remain metabolically active to maintain the senescence program. However, the mechanisms behind this metabolic reprogramming are not well understood. We identify senescence-induced long noncoding RNA (sin-lncRNA), a previously uncharacterized long noncoding RNA (lncRNA), a key player in this response. While strongly activated in senescence by C/EBPβ, sin-lncRNA loss reinforces the senescence program by altering oxidative phosphorylation and rewiring...

Aging is a complex biological process that detrimentally affects the brain and cerebrovascular system, contributing to the pathogenesis of age-related diseases like vascular cognitive impairment and dementia (VCID) and Alzheimer's disease (AD). While cell-autonomous mechanisms that occur within cells, independent of external signals from neighboring cells or systemic factors, account for some aspects of aging, they cannot explain the entire aging process. Non-autonomous, paracrine and endocrine,...

CONCLUSION: This study reveals the complex relationship between cognitive function, internet use, and physical activity in older adults, and provides new perspectives for interventions aimed at improving cognitive health in older adults. Future research should further explore the dynamic changes between these variables to develop more effective intervention strategies and improve cognitive health and well-being in older adults.

Preservation of synapses is crucial for healthy cognitive ageing, and synapse loss is one of the closest anatomical correlates of cognitive decline in Alzheimer disease, dementia with Lewy bodies and frontotemporal dementia. In these conditions, some synapses seem particularly vulnerable to degeneration whereas others are resilient and remain preserved. Evidence has highlighted that vulnerability and resilience are intrinsically distinct phenomena linked to specific brain structural and/or...

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DNA methylation clocks have been widely used for accurate age prediction, but most studies have been carried out on mammals. Here we present an epigenetic clock for the aquatic frog Xenopus tropicalis, a widely used model organism in developmental biology and genomics. To construct the clock, we collected DNA methylation data from 192 frogs using targeted bisulfite sequencing at genomic regions containing CpG sites previously shown to have age-associated methylation in Xenopus. We found highly...

Aging results in a progressive decline in physiological function due to the deterioration of essential biological processes. While proteomics offers insights into aging mechanisms, prior studies are limited in proteome coverage and lifespan range. To address this, we integrate the Orbitrap Astral Mass Spectrometer with the multiplex tandem mass tag (TMT) technology to profile the proteomes of cortex, hippocampus, striatum and kidney in the C57BL/6JN mice, quantifying 8,954 to 9,376 proteins per...