Aging & Longevity

Emerging evidence implicates premature placental senescence as a central driver of pregnancy complications, though its underlying mechanisms remain elusive. Here, we report marked downregulation of IL33 (interleukin 33) in villi from unexplained recurrent pregnancy loss (URPL) patients, concomitant with elevated trophoblast senescence. More importantly, il33 knockout mice exhibited placental senescence and impaired trophoblast invasion. Mechanistically, senescent trophoblasts displayed metabolic...

Activation of RAS oncogenes in normal cells triggers a stable cell cycle arrest known as RAS-induced senescence (RIS), marked by persistent DNA damage and extensive epigenetic remodeling. Although bypassing RIS promotes tumorigenesis, the molecular mechanisms underlying this transition remain poorly defined. Here, we demonstrate that RIS cells accumulate high levels of R-loops-three-stranded DNA-RNA hybrids-that frequently co-localize with DNA G-quadruplexes formed on the non-template DNA...

Telomere healing seals the broken ends of DNA double-strand breaks by adding de novo telomeres. In the ciliate Paramecium, telomere healing results in chromosome fragmentation, which ultimately leads to clonal ageing. Despite its importance, where and how chromosomes fragment and undergo telomere healing, and to what extent sequence preferences exist, remain poorly understood. To investigate chromosome fragmentation, we enriched for telomere-containing sequences from the complex, highly...

Some organisms exhibit a remarkable ability to adapt their life history strategies within a single lifespan in response to dynamic biotic and abiotic cues, such as Caenorhabditis elegans larval facultative diapause. However, the molecular basis of how conspecific and prey cues are processed to conditionally alter the time to reproductive maturation remains largely unexplored. Here we discover that the longest transcript of the forkhead transcription factor FKH-7/FOXP is expressed and acts in C....

In populations of many animal species, including humans, mortality rates increase exponentially with advancing age. The scale and rate of increase can be set by two parameters, α and β, respectively, of the Gompertz equation. Interventions that extend lifespan can reduce either or both parameters. A long-standing supposition is that β corresponds to biological ageing rate, and α to ageing-independent causes of mortality. Here, we investigate the biological basis of α and β using the nematode...

The retina provides a unique window into systemic health, yet molecular mechanisms linking retinal features (oculomics) to clinical traits in aging remain unclear. In this study, we leveraged the homogeneous Canton 70 s Alumni Cohort (N = 258 females aged ~70 years) to minimize socio-demographic confounders and extracted oculomic features from fundus images using AutoMorph. Linear mixed-effects models identified 129 significant associations between oculomic and clinical features (p < 0.05)....

Caloric restriction (CR) extends lifespan across diverse organisms, but the effects of CR on human aging and on healthspan are only beginning to be uncovered. In this study, we applied proteomics to plasma samples collected longitudinally from participants achieving, on average, 14% CR over 2 years as part of the CALERIE trial. We identified that inhibition of the complement pathway is linked to lower inflammaging. In humans, the C3a/C3 ratio was significantly lowered by CR, thus reducing...

Aging is the strongest risk factor for Alzheimer's disease (AD), yet the role of age-associated DNA methylation (DNAm) changes in blood and their relevance to AD remains poorly understood. We performed a meta-analysis of blood DNAm samples from 475 dementia-free subjects aged over 65 years across two independent cohorts, the Framingham Heart Study (FHS) at Exam 9 and the Alzheimer's Disease Neuroimaging Initiative (ADNI). We adjusted for sex and immune cell-type proportions and corrected batch...

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Cognitive flexibility supports efficient switching between mental sets and contributes to the preservation of general cognition in aging. It relies on the integration between brain functional dynamics and structural architecture. However, how this structure-function integration changes with age and contributes to cognitive flexibility decline in older adults remains unclear. In this study, we investigated longitudinal aging-related changes in multimodal structure-function integration, quantified...

INTRODUCTION: The human brain exhibits complex functions that emerge from interactions among spatially distributed neural regions. Electroencephalography (EEG) microstate analysis has been widely adopted to capture transient topographies reflecting large-scale network dynamics; moreover, it has been linked to cognitive functions, intrinsic brain networks, and neuropsychiatric disorders. Building on this framework, we recently proposed a novel approach based on instantaneous frequency (IF),...

CONCLUSION: Older women with higher NC values showed greater cardiovascular risk and lower relative muscle strength, but no difference in functional test performance (sit to stand, biceps curl, TUG, and 6MWT performance). These findings support NC as a practical and low-cost anthropometric indicator of cardiovascular risk in older women.

Gut microbiota (GM) plays a crucial role in maintaining health through metabolic, endocrine and immune functions. With ageing, shifts in GM composition, characterised by increased pathogenic and decreased health-promoting bacteria, contribute to dysbiosis, which is linked to several age-related diseases. Given the global trend of increasing sedentary behaviour (SB) and declining physical activity (PA) among older adults, this study aims to explore the relationships between GM and two critical...

CONCLUSIONS: Resilience and social support were independently and jointly associated with cognitive function among middle-aged and older adults. These associations appeared to be stronger in women, although variation by sex was observed. Given the cross-sectional design, the findings should be interpreted as exploratory, and further longitudinal and interventional studies are needed to clarify the role of psychosocial resources in cognitive ageing.

Age-related cognitive and exploratory decline is a hallmark of brain aging across species, yet the evolutionary conservation of specific behavioral phenotypes remains unresolved. Thigmotaxis, the wall-following preference in open-field exploration, serves as a robust index of anxiety and cognitive vulnerability in humans and rodent models of aging and neurodegeneration. Here, we report that house crickets (Acheta domesticus) exhibit steep age-related increases in thigmotaxis, mirroring...

Cognitive decline with age is characterized by impairments in learning, sensory discrimination, and decision-making. While mammalian models have advanced understanding of the neural substrates of aging, their use in large-scale behavioral studies is limited. Invertebrate models, such as the house cricket (Acheta domesticus), offer short lifespans, high throughput, and conserved neurobiological pathways but remain underexplored in geroscience. We developed a dual behavioral paradigm integrating...

Increased napping in later life is a common behaviour shaped by cultural, environmental and biological factors. Although brief naps can enhance alertness and memory, epidemiological evidence suggests that frequent or prolonged daytime sleep in older adults is associated with poorer physical health and accelerated cognitive decline, including episodic memory, possibly due to the underlying circadian disruption of the sleep-wake cycle. In this study, we tested whether restricting nap habits for 12...

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