Aging & Longevity

Natural killer (NK) cells, a type of potent cytotoxic lymphocyte, are particularly promising for the treatment of cancers that lose or downregulate major histocompatibility complex class I (MHC class I) expression to evade T cell-mediated immunotherapy. However, the hostile and immunosuppressive tumor microenvironment (TME) greatly hinders the function of tumor-infiltrating NK cells, thus limiting the therapeutic efficacy. Here, we show a fusion protein of interleukin 21 (IL-21-Fc) that safely...

Whole genome sequencing (WGS) studies in large biobanks provide an unprecedented opportunity to study the rare-variant (RV) effects on the natural history of human diseases by analyzing censored time-to-event (TTE) phenotypes, such as age at disease diagnosis, disease progression, and lifespan. Unlike existing methods developed for continuous and categorical phenotypes, rare-variant association tests (RVATs) for TTE phenotypes in large biobanks face several major challenges, including heavy...

Environmental stressors-induced male infertility has become a major public health issue. Sperm motility is the key to conception. However, the immunological mechanism for environmental stress-induced sperm motility reduction remains unknown. Our experiments find that three classical environmental stressors, including lead, cadmium, and mercury, are the key heavy metals reducing sperm motility. We reveal that environmental stress induces epididymal macrophage senescence, whereas the clearance of...

Glasses have complex energy landscapes and exhibit nonequilibrium aging dynamics. Here, we propose a generalized trap model for activated aging based on a key static property of the energy landscape: the distribution of energy barriers. Our theory predicts that, upon cooling, weak ergodicity breaking (WEB) in quenching dynamics occurs before strong ergodicity breaking in equilibrium dynamics. Furthermore, the theory indicates that the characteristic size of activation clusters can be deduced...

ObjectivesThe older population and prevalence of frailty are increasing worldwide. Understanding how midlife exposures influence frailty risk is increasingly important for public health. This review sought to identify modifiable risk factors present in midlife that are associated with the onset of frailty in later life, aiming to inform earlier prevention strategies.MethodsWe conducted a systematic review of studies examining modifiable risk factors in community-dwelling adults aged 39-64 years,...

INTRODUCTION: β-hydroxybutyrate (BHB) has been linked to improved cognitive function via enhanced cerebral metabolism and anti-inflammatory effects. However, evidence on the relationship between endogenous plasma BHB levels and cognitive decline remains limited. This study investigated whether higher plasma BHB levels are associated with reduced cognitive decline in middle-aged and older adults.

Air pollution accelerates biological aging via oxidative stress and inflammation, a process potentially mitigated by plant-based diets. However, the role of dietary or genetic modulators in this relationship remains understudied. Our study aimed to examine whether adherence to Sustainable Diets modifies the associations of PM(2.5) and PM(10) exposure with biological aging, and to assess potential effect modification by genetic susceptibility to longevity. Data from 9527 participants in the...

Skin aging has traditionally been attributed to alterations in the epidermis and dermis, including keratinocyte senescence, extracellular matrix (ECM) degradation, and fibroblast dysfunction. In contrast, the role of skin-associated adipose tissue (SAAT), particularly dermal white adipose tissue (dWAT), has been largely overlooked and considered a passive structural filler. Emerging evidence indicates that adipocyte aging is not merely a consequence of skin aging but may serve as a critical...

Circular RNAs (circRNAs) accumulate with age, but their functional impact on aging remains elusive. In this study, we reveal a mechanism by which ribonuclease κ (RNASEK) prevents age-dependent circRNA accumulation by promoting its degradation. Through a genetic screen targeting ribonucleases, we identified RNASEK as a specific circRNA-cleaving ribonuclease. RNASEK is downregulated during aging, causing the age-dependent increase in circRNA levels. RNASEK is necessary and sufficient for lifespan...

Astaxanthin (AST), a xanthophyll carotenoid derived from microalgae and marine organisms, has emerged as a potent neuroprotective compound with remarkable antioxidant and anti-inflammatory properties. Growing evidence indicates that AST can modulate multiple molecular and cellular pathways involved in neuronal survival, synaptic plasticity, learning, and memory, particularly in the context of neurodegenerative aging. This review provides an up-to-date and integrative overview of current evidence...

CONCLUSION: The results suggest that oxytocin modulates stress responses, oxidative balance, and inflammatory pathways in aged rats subjected to chronic sleep deprivation. Although the precise central mechanisms remain unresolved, these findings support a potential role for oxytocin in mitigating SD-associated pathophysiological changes in aging and warrant further mechanistic studies to clarify its neuroprotective potential.

Early-life nutrition can exert long-lasting effects on later-life health. Given that lactose is extensively consumed during early mammalian development, this raises the intriguing possibility that lactose or its constituent galactose may exert beneficial nutritional programming effects. We tested here whether early-life (larval period) co-consumption of galactose and glucose (GALGLU; as in hydrolysed lactose) shapes later-life (adult) lifespan in Drosophila melanogaster. Larval GALGLU versus...

Epigenetic clocks are commonly used aging biomarkers based on DNA methylation that predict long-term morbidity and mortality risk. Increased cellular senescence with age is also posited to contribute to age-related disease and mortality. However, prior studies have found that existing epigenetic clocks show inconsistent associations with cellular senescence and no reductions after senolytic treatment. We hypothesize this reflects that senescence-related CpGs are a small proportion of age-related...

Ageing is a progressive biological process causing a reduction in tissue and cellular function due to accumulated molecular damage over time. Cellular senescence is a stable cellular state characterized by irreversible cell-cycle arrest accompanied by distinct molecular, epigenetic, and secretory alterations. Moreover, neuroendocrine signalling and epigenetic regulation have had a great impact on controlling ageing and senescence. As a part of the neuroendocrine system, the...

CONCLUSION: These findings highlight the importance of early prevention strategies to address polypharmacy, muscle loss, and low education, all of which are potentially modifiable risk factors. Poorer physical performance was linked to polypharmacy, low muscle mass, and lower educational levels, suggesting a need for additional research into these contributing risk factors.

To investigate organism-wide cellular alterations and epigenomic dynamics during aging, we constructed a single-cell chromatin accessibility atlas spanning 21 mouse tissues across three age groups and both sexes. We found that around one-quarter of 536 organ-specific cell types and 1828 finer-grained subtypes exhibited considerable age-related population shifts. Cellular states from broadly distributed lineages displayed synchronized dynamics with age, indicating systemic signals that coordinate...

Age-related chromatin remodeling includes shared and specific signatures across cell types, sex, and organs.

CONCLUSIONS: Despite limited guidance on methods and biomarkers, this scoping review supports MRS as a promising tool for monitoring exercise-induced metabolic changes in muscle and brain of older adults. However, standardized methodologies and larger number of studies are required to determine which metabolites reliably reflect exercise benefits in aging brain and muscle.

Pancreatic cancer is a highly aggressive tumor with a poor prognosis. The ubiquitin-proteasome system is crucial in maintaining protein homeostasis and regulating cellular senescence, thereby influencing tumorigenesis and progression; however, the specific mechanisms underlying this process remain unclear. Ubiquitin protein ligase E3A (UBE3A) is associated with various tumors; however, its potential role in pancreatic cancer warrants further investigation. The effects of UBE3A on cellular...

The self-renewal capacity of intestinal stem cells (ISCs) declines with aging, leading to a loss of homeostasis and an increased susceptibility to intestinal diseases. Despite the established significance of lipid metabolism and epigenetic regulation in ISC function, the molecular mechanisms that connect these processes to aging-related ISC dysfunction remain elusive. Here, we hypothesize that histone 3 lysine 36 trimethylation (H3K36me3) might act as a bridge between these processes. In this...