Aging & Longevity

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^(+)...

A critical challenge in sepsis treatment lies in its complex immune microenvironment, characterized by concurrent hyperinflammation and immunosuppression. This imbalance is jointly driven by dysregulated neutrophil programmed death and abnormal activation of the PD-1/PD-L1 immune checkpoint. Therefore, precisely modulating neutrophil fate and blocking this immune checkpoint are highly promising therapeutic strategies. We engineered an artificial exosome nano-decoy (AT@NV-PD1) that homes to...

Ageing is an inevitable, yet highly heterogeneous process shaped by genetic, epigenetic, and environmental influences. While most individuals experience progressive functional decline, a minority exhibits accelerated degeneration due to rare pathogenic mutations, whereas others achieve exceptional healthy longevity. This continuum-from progeroid syndromes to centenarians-provides a unique framework to examine how deleterious and protective genetic variants differentially modulate conserved...

The Hallmarks of Aging framework has become a widely accepted schema within geroscience, organizing diverse mechanisms of cellular and molecular decline. This article examines whether the Hallmarks function as a scientific paradigm and, beyond that, whether they have enabled genuine scientific progress-an angle largely absents from current literature. Drawing on models from the philosophy of science, the article evaluates the framework's status and impact from multiple perspectives. From Kuhn,...

CONCLUSIONS AND IMPLICATIONS: Participation in community gatherings is associated with reduced LTC costs among older adults with mild disabilities under the LTCI system. These programs may promote more efficient use of care resources and support municipal strategies to contain LTC costs.

CONCLUSIONS AND IMPLICATIONS: Home care and dementia were the primary drivers of nursing home entry in Sweden between 2020 and 2022, while social factors played a smaller role. Further investigations should ensure that those with dementia who are living alone or have multimorbidity are receiving adequate care. With continued population aging, it is essential that we monitor and adapt our policies and systems to ensure needs dictate access to care.

Mutations accumulate with age in most human tissues. While some undergo clonal expansion and contribute to disease, the mutational burden tolerated by a normal cell without functional decline remains unknown. Here, we repeatedly treat proliferating human primary fibroblasts with the point mutagen N-ethyl-N-nitrosourea, and analyze mutation burden by single-cell whole-genome sequencing. Mutation burden increases linearly to ~56,000 single-nucleotide variants per cell, with only a modest reduction...

Dielectric elastomers are soft electroactive polymers capable of large-strain actuation with the moniker artificial muscle. However, current dielectric elastomers exhibit limited operational stability when operated at strain and energy density in the neighborhood of natural muscles, due to mechanical fatigue or electrical breakdown. In this work, we design a dielectric elastomer comprising a bimodal network structure and zwitterionic side groups to overcome electro-mechanical instability and...

Age-related decline of the neuromuscular junction (NMJ), the peripheral synapse that controls muscle contraction, contributes to muscle weakness and impaired motor function in aging. The NMJ comprises a motor axon terminal, a skeletal muscle fibre, and terminal Schwann cells (tSC). Neurotrophin signalling is essential for mature NMJ organisation, with the p75 receptor acting as a key regulator of its morphology and function. However, the potential contribution of p75 to age-related NMJ decline...

Vaginal aging is a multifactorial biological process characterized by structural, functional, and molecular alterations driven primarily by estrogen decline. This review summarizes current evidence on potential biomarkers across five domains: physiological parameters, imaging features, histological changes, and molecular alterations. We further discuss methodological challenges and future research directions necessary to establish standardized and clinically applicable biomarkers. Understanding...

Clove (Syzygium aromaticum) extracts promote longevity in several model systems, yet the underlying molecular mechanisms responsible for the pro-longevity remain poorly defined. This study utilized a Saccharomyces cerevisiae model to investigate how clove extracts modulate two primary hallmarks of cellular aging: oxidative damage and the decline of protein quality control systems. Clove extracts promoted increased chronological lifespan (CLS) of yeast cells. The change in longevity was...

Aging is accompanied by a progressive decline in intestinal barrier integrity, resulting in increased permeability to luminal microbes and microbial products and contributing to chronic low-grade inflammation ("inflammaging"). While epithelial and microbial changes have been extensively studied, the role of intestinal T cells as active regulators of barrier homeostasis during aging remains underappreciated. The gut harbors the largest population of T cells in the body, including diverse...

CONCLUSIONS: Loneliness emerged as the factor most consistently associated with emotional distress in older adults. These findings underscore the importance of designing public policies and psychosocial interventions focused on reducing unwanted loneliness and strengthening social connectedness in both institutional and community settings.

CONCLUSIONS: Self-reported driving concerns demonstrate predictive validity for future crashes, but a substantial minority of crash-involved drivers remain undetected by self-report. Education and TMT-B performance may serve as clinically actionable markers for identifying these "silent" at-risk drivers.