Aging & Longevity

Flap endonuclease 1 (FEN1), a key enzyme in DNA metabolism, exhibits oncogenic properties in various cancers. However, its functional role and underlying mechanisms in lung adenocarcinoma (LUAD) progression and tumor immunity remain poorly defined. Here, we demonstrate that FEN1 is significantly upregulated in LUAD tissues and serves as an independent prognostic factor for poor survival. Genetic depletion of FEN1 suppressed LUAD cell proliferation by inducing G0/G1 cell cycle arrest and cellular...

Ageing is accompanied by a progressive decline in homeostatic resilience that increases vulnerability to chronic disease, disability and cognitive impairment. Although unhealthy brain ageing can often be prevented by managing the underlying risk factors, the molecular, cellular and physiological mechanisms that connect risk factors to late-life brain dysfunction remain incompletely understood. This review examines the role of the endocannabinoid system in brain ageing. The endocannabinoid system...

Aging is accompanied by progressive functional decline and morphological defects of cholinergic neurons. Some probiotic bacteria with proficiency for biofilm formation in the gut are being discussed as potentially neuroprotective. Here, we screened Bacillus subtilis (B. subtilis) strains for biofilm production, using an in vitro assay. Thereafter, a transgenic Caenorhabditis elegans (C. elegans) strain with its cholinergic neurons expressing green fluorescent protein (GFP) was fed for up to 15...

S-adenosyl-L-methionine (SAM) is a fundamental methyl donor; however, the physiological role of its byproduct and competitive inhibitor, S-adenosyl-L-homocysteine (SAH), remains unclear. Here, we show that transient reactive oxygen species (ROS) production triggered by SAH during the early logarithmic phase mimics partial SAH hydrolase inhibition, extending the yeast chronological lifespan (CLS) through a hormetic mechanism. This study reveals that the dual nature of ROS in aging is determined...

Electronic textiles represent a transformative platform for integrating technology into daily wear, yet their development has been undermined by a fundamental challenge: the conflicting requirements between mechanical deformation for functionality and structural stability for performance. This challenge is particularly acute in cylindrical fiber electrodes, where inherent nonuniform electric field distribution leads to dendrite formation and poor active material utilization-problems that are...

The role of senescent tumor cells in modulating the immune microenvironment and influencing immunotherapy efficacy remains poorly understood. In this study, we investigate the function of the senescence-associated gene membrane magnesium transporter 1 (MMGT1) in triple-negative breast cancer (TNBC) immunotherapy. MMGT1 is upregulated in TNBC and correlates with poor prognosis. Mammary gland-specific knockout of Mmgt1 significantly impedes tumor growth. Mechanistically, MMGT1 promotes lipid...

Aging is frequently accompanied by profound alterations in the chromatin landscape, leading to widespread changes in transcriptional programs and cellular functions. Forkhead box O (FOXO) proteins, traditionally viewed as downstream effectors of insulin and stress-response signaling, are now emerging as dynamic chromatin regulators that integrate metabolic cues with epigenetic remodeling during aging. In this review, we first outline the major epigenetic and chromatin alterations associated with...

Ageing profoundly impairs vaccine efficacy, leaving older individuals highly susceptible to infectious diseases despite vaccination. Although B cells retain the intrinsic capacity to generate germinal centre (GC) responses in older people, age-associated defects in T cells, dendritic cells and follicular dendritic cells (FDCs) limit the development of high-affinity, class-switched antibody responses. Here, we hypothesised that senescent fibroblasts disrupt B cell activation and expansion, thus...

CONCLUSIONS: In this post-hoc analysis, group allocation was not associated with lower body weight at follow-up. Despite high levels of motivation and confidence regarding weight loss and favorable changes in diet and physical activity in the intervention group, these changes did not translate into measurable weight loss.

Chronic metabolic stress is increasingly recognized as a driver of aging-like tissue dysfunction, but whether it durably reprograms liver regenerative cells, potentially compromising tissue maintenance and repair, remains unknown. Here, we show that high-fat diet (HFD)-induced metabolic stress promotes a persistent senescence-like state in the liver regenerative compartment. In male rats, chronic HFD feeding induced hepatic steatosis together with oxidative stress, inflammatory responses, and...

Vascular endothelial cell (VEC) senescence drives organismal aging and age-related pathologies, yet the intrinsic factors preserving endothelial youthfulness remain poorly defined. Here, we identify MTR4, an evolutionarily conserved RNA helicase and nuclear RNA exosome cofactor, as a novel regulator of VEC senescence. MTR4 protein declines markedly in senescent HUVECs and aged mouse aortas, independent of general cell cycle exit. Mechanistically, senescence-induced upregulation of the E3...

Population-based studies on the relation between polygenic longevity scores (PGLSs) and specific brain regions on magnetic resonance imaging (MRI) are few. We aimed to investigate this relationship in a population of 70-year-olds from Gothenburg, Sweden (N = 675). We constructed two PGLSs (one with and one without the APOE locus) using longevity GWAS summary statistics. MRI outcomes included total grey matter, white matter (WM), WM hyperintensities (WMHs), subcortical volumes, small vessel...

Cognitive reserve theory posits that compensatory mechanisms during aging stave off cognitive decline and lower risk for Alzheimer's disease. Here, in a screen for hippocampal dentate granule cell (DGC) synapse loss-induced factors in mice, we identified a secreted phospholipase, Pla2g2f, whose expression increases in DGCs during aging and is associated with cognitive resilience in humans. Pla2g2f deletion in DGCs exacerbates aging-associated pathophysiological changes, including synapse loss,...

Oxidative stress resistance is an important trait that contributes to the long lifespan of Drosophila melanogaster, but its epigenetic inheritance via transgenerational transmission has been poorly studied. In this study, using reciprocal crosses between normal-lifespan (NLS) and long-lifespan (LLS) lines, we investigated the transgenerational inheritance of paraquat-induced oxidative stress resistance across the parental, F(1), and F(2) generations, assessing survival, locomotor performance,...

Age-related changes in hepatocyte ploidy, binucleation, proliferative activity, and senescence-associated cell-cycle arrest may jointly influence liver regenerative capacity, but these features are usually evaluated separately. We developed two composite indices and examined their behavior in a long-term rat model of chronic circadian disruption. Male Wistar rats were assigned to control lighting, constant illumination (dark deprivation; DD), or constant illumination with melatonin (DD +...

Metabolic homeostasis and female reproductive health are governed by tightly coupled regulatory systems, yet their reciprocal interactions have often been investigated in isolation. In this Review, we synthesize current epidemiological, mechanistic and clinical evidence to propose an integrated framework in which dynamic, bidirectional crosstalk between key metabolic organs and endocrine mediators constitutes a central determinant of female reproductive function across the life course. We...

Aging-associated intestinal dysfunction is characterized by impaired epithelial homeostasis, excessive intestinal stem cell (ISC) proliferation, and progressive barrier deterioration. Although oxidative stress is widely recognized as a major driver of intestinal aging, the mechanisms linking redox imbalance to ISC dysregulation remain incompletely understood. In this study, we investigated the effects of dietary chlorogenic acid (CGA) treatment using Drosophila models of physiological aging,...

CONCLUSIONS: Self-reported gait speed and grip strength measures demonstrated limited validity compared with objective assessments in older adults with mild frailty and should be used cautiously as substitutes for measuring weakness and slowness in this population. Trial Registration: ISRCTN Registry: ISRCTN54268283.

Hutchinson-Gilford progeria syndrome (HGPS) is a rare premature aging disorder most commonly caused by a de novo synonymous mutation (c.1824C>T) in the LMNA gene. This mutation activates aberrant splicing of prelamin A, leading to the production and accumulation of progerin, which drives accelerated aging, with patients predominantly succumbing to cardiovascular disease. However, while cardiac pathologies are well documented, the cell-autonomous contribution of cardiomyocytes to HGPS-associated...

Mitochondria are central regulators of retinal bioenergetics and innate immune signaling, yet how mitochondrial genetic background and aging jointly influence immunometabolic responses in the retina remains poorly defined. Here, we investigated the effects of mitochondrial DNA (mtDNA) variation on retinal function and the combined effects of mtDNA variation and age on bioenergetic composition, mtDNA damage, and the microglial expression and intracellular localization of stimulator of interferon...