Aging & Longevity

Loss of host-microbiota balance promotes gut inflammation, colitis and inflammatory bowel disease. Yet, whether host or microbial factors are the critical driver of the pathology remains unclear. Here, we investigate how cardiolipin maintains metabolic fitness of regulatory T (T(reg)) cells to preserve gut-immune homeostasis. We discover that deleting the cardiolipin-synthesizing enzyme protein tyrosine phosphatase mitochondrial 1 (PTPMT1) in T cells predisposes mice to colitis due to impaired...

Disease-associated microglial states are thought to contribute to Alzheimer's disease (AD) progression, but characterizing them and their relationships to pathology remains challenging. Here we introduce CODEX-CNS-a multiplexed protein imaging technology with a custom data analysis pipeline for use in human brain samples. We profiled 704,706 cells in samples from the frontal cortex of 8 people with AD and 8 healthy controls and mapped features including blood-brain barrier, meningeal components...

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Population ageing has led to an increase in prevalence of old-age disability but whether the risk of disability can be detected early remains unclear. We used ten functioning/fitness measures in early old-age to identify their predictive ability for disability at older ages. A total of 4593 participants of the Whitehall II study, mean age 65.3 years, were followed for a median of 11.00 (IQR 7.25-12.67) years for incident disability [≥ 1 limitation in activities of daily living (ADL)], and severe...

CONCLUSION: Targeted digital literacy programs and age-friendly technology designs are essential for maintaining cognitive health in older populations.

INTRODUCTION: Age-related declines in cognitive and motor functions show highly variable trajectories. To better understand the underlying mechanisms, we investigated multivariate associative effects between modifiable vascular risk factors, biological brain aging, cognitive, and motor performance in 40,579 individuals from the population-based UK Biobank and Hamburg City Health Study.

INTRODUCTION: Alzheimer's disease (AD) is strongly associated with cerebrovascular dysfunction and impaired glymphatic clearance. These dysfunctions may precede, contribute to, and interact bidirectionally with AD pathology, highlighting the importance of identifying physiological markers for the early detection of AD. Noninvasive approaches for assessing these processes and identifying early biomarkers remain limited. Cerebrospinal fluid (CSF) plays a central role in clearing neurotoxins from...

Senescent cells accumulate with age following stress-induced cell cycle arrest triggered by DNA damage, oncogene activation, and replicative exhaustion. While they contribute to tissue repair and tumor suppression, their persistent senescence-associated secretory phenotypes (SASPs) drive age-related diseases. The heterogeneity of senescent cell populations, particularly the distinction between primary and secondary senescence, remains incompletely understood at single-cell resolution. Here, we...

Ribosomes consist of approximately 80 distinct ribosomal proteins and rRNA. The genes encoding these ribosomal components are among the most highly expressed in growing cells. Changes in ribosome composition, such as those induced by oxidative stress, may compromise ribosome function. Such ribosomes are subsequently targeted for degradation. Additionally, under stress, both protein synthesis and ribosome biogenesis are downregulated. Under starvation stress, excess ribosomes are degraded through...

Improving cognitively healthy survival is important for achieving healthy aging. Therefore, it would be valuable to estimate the future risk of either incident dementia or death in community-dwelling older adults. This study aimed to develop a set of risk prediction models for either incident dementia or death that can be applied according to data availability across diverse clinical settings, using longitudinal data from community-dwelling older Japanese adults. A total of 8,334 participants...

Geroscience needs biomarkers that capture the progressive decline of integrated biological systems with age. Physical capacity, a direct manifestation of systemic integrity, is a core pillar of biological aging but is typically assessed through discrete clinical tests. Speech production, a complex motor act requiring coordinated respiratory, laryngeal, and articulatory control, shares fundamental physiological pathways with global physical function and may therefore serve as an accessible...

Microglial senescence has emerged as a potentially important aging-related mechanism in Alzheimer's disease (AD), shaped in part by epigenetic reprogramming and closely coupled to immunometabolic dysfunction. While microglia initially mount adaptive responses to amyloid-beta (Aβ), tau, and tissue stress, persistent exposure to chronic neurodegenerative cues may drive subsets of microglia toward senescence-like states characterized by altered chromatin regulation, transcriptional remodeling,...

The genotoxic agent doxorubicin induces premature vascular aging, defined by vascular endothelial dysfunction and aortic stiffening. Excess vascular cell senescence and the accompanying senescence-associated secretory phenotype (SASP) are key mechanisms underlying doxorubicin-induced vascular dysfunction, in part, by promoting excess mitochondrial oxidative stress, which reduces the bioavailability of the vasodilatory molecule nitric oxide (NO). In the present study, we assessed if the natural...

Estrogens are pleiotropic hormones that regulate reproductive and non-reproductive physiological processes in both sexes. Among these, 17α-estradiol (17α-E2), a C17 epimer of the canonical estrogen 17β-estradiol (17β-E2), has emerged as a promising modulator of aging and metabolism with sexual dimorphism. Unlike 17β-E2, which exerts broad estrogenic effects in both sexes, 17α-E2 extends lifespan and preferentially improves metabolic homeostasis in male mice while inducing only mild feminizing...

Age-related cognitive impairment poses a significant public health challenge. Although exercise interventions have been shown to ameliorate cognitive deficits, the underlying molecular mechanisms remain incompletely understood. This review therefore proposes a novel framework, based on current evidence, integrating exercise interventions with the D-amino acid oxidase (DAO)/D-serine-N-methyl-D-aspartate receptor (NMDAR) axis. This review explores the potential mechanisms by which exercise...

Electrochemical reactions are generally accompanied by mechanical evolutions, which, in turn, play a critical role in the performance of the electrochemical system. In aqueous Zn||MnO(2) batteries, the intrinsically structural instability of MnO(2) and rampant side reactions create considerable strain/stress changes in operation. However, the electrochemistry-mechanics-performance relationship of the Zn||MnO(2) cell is still missing. Herein, we decode the electrochemomechanical interplay of...

The brain age gap (BAG), the difference between magnetic resonance imaging-predicted brain age and chronological age, is a proposed marker of neurobiological aging, yet its transdiagnostic significance remains uncertain. This meta-analysis evaluated BAG in Alzheimer's disease (AD), mild cognitive impairment (MCI), multiple sclerosis (MS), Parkinson's disease (PD), schizophrenia (SCZ), stroke, and bipolar disorder (BD) to determine shared and disorder-specific patterns of accelerated brain aging....

Oxylipins, signalling molecules derived from polyunsaturated fatty acids, act as key mediators controlling inflammatory processes. Ageing fuels the disruption of this network, promoting inflammageing. Social isolation, a common feature of ageing, may contribute to the emergence of pro-inflammatory responses, further aggravating conditions like cognitive decline and frailty. Here, we studied how repeated social isolation impacts inflammation-related oxylipin profiles in seven different organs and...

Blood inflammatory marker studies in aging and Alzheimer's disease (AD) research have faced numerous interpretative and methodological challenges that have hindered the field's understanding of the relationship between immune network regulation/dysregulation and aging health factors. We examined how blood inflammation markers directly relate to each other in typical aging, cognitively unimpaired adults using a conditional network analytic modeling approach. We further evaluated how blood...

Changes in peripheral CD8^(+) T cells are a hallmark of immune aging. However, the role of aged non-infiltrating CD8^(+) T cells in brain aging remains to be fully defined. Here, we showed that aged circulating CD8^(+) T cells and their secreted factors drove hippocampal-dependent cognitive decline. Using heterochronic parabiosis and transcriptomics analysis, we observed that peripheral CD8^(+) T cells maintained properties intrinsic to their age. Systemic exposure of young mice to aged CD8^(+)...