Aging & Longevity

INTRODUCTION: Sleep quality is often thought to be a key determinant of cognitive performance, particularly in older adults who experience age-related changes in sleep architecture. However, the extent to which nightly variations in sleep quality impact next-day cognitive performance remains unclear-in part because it has only recently become practical to measure sleep over multiple nights.

Accurate age estimation is key to understanding life history, population ecology, and effective management of valuable commercial and ecologically relevant species. While DNA methylation-based epigenetic clocks are well developed in mammals, their application in fish is limited. In contrast to mammals, fish lack identified universal fish epigenetic markers. Here we explore the potential of ultra-conserved elements (UCEs) as age predictor markers in albacore tuna (Thunnus alalunga), a worldwide...

In a little over 100 years, global life expectancy has increased by ∼60%. Paradoxically, it has been estimated that we now exercise five times less than we did 100 years ago. Despite a marked increase in life expectancy, the prevalence of non-contagious diseases (NCDs), otherwise known as "chronic lifestyle diseases," such as cardiovascular disease, type 2 diabetes, cognitive diseases, and cancer, has increased. Here, we discuss the concept of "exercise as medicine" for the treatment of NCD and...

DNA damage and mutations in hematopoietic stem cells (HSCs) enable clonal hematopoiesis (CH). Such damage occurs across a lifetime, but its origins remain unknown. Here, we demonstrate that endogenous formaldehyde causes HSC attrition and subsequently CH. We generated conditional mouse models lacking formaldehyde detoxification and Fanconi anemia (FA) DNA repair in blood. Formaldehyde protection was crucial for embryonic HSC emergence and throughout life. Despite severe deficiencies in HSCs,...

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Cataract is a leading cause of visual impairment worldwide, and its prevalence is increasing with population aging. The majority are age-related cataracts (ARC), clinically classified into nuclear, cortical, and posterior subcapsular cataracts (PSC) by opacity location. Mechanisms of cataractogenesis remain incompletely understood. While cortical and nuclear cataracts are largely attributed to crystallin aggregation, such protein-centric mechanisms fail to explain the early onset and axial...

CONCLUSION: Neighbourhoods play a crucial role in supporting older adults' flourishing, but evidence on causal pathways and life-course dynamics remains limited. The proposed integrative framework enhances conceptual clarity and provides a foundation for longitudinal research to guide place-based interventions for positive ageing.

With age, human skin undergoes a progressive decline in essential functions, including barrier protection, immunity, and wound healing capacity, which underlie many age-related skin diseases. Skin aging is not only driven by chronological aging, but also strongly influenced by extrinsic stressors, notably ultraviolet radiation, pollutants, and diet. Thus, understanding the complex interplay between these intrinsic and extrinsic factors is essential for developing strategies to preserve skin...

Frailty is an established benchmark of aging-related decline, yet most measures of frailty focus on physical decline. Increasing evidence that social environments influence trajectories of aging has led to growing interest in social frailty. Recently, a 10-item Social Frailty Index (SFI-10) was developed using data from the Health and Retirement Study (HRS) that used 8 social items plus chronological age and sex to predict mortality. This study evaluates the validity of the SFI-10, providing...

Interorgan communication is essential for metabolic homeostasis and healthy aging, with adipose tissue acting as a central hub that coordinates systemic metabolism, stress responses, and longevity. Here, we show that the miRNA-processing enzyme Dicer-1 (Dcr-1) acts in the fat body (FB) to regulate Dilp2 secretion from brain insulin-producing cells (IPCs), thereby modulating systemic insulin signaling and lifespan in Drosophila. Dcr-1 expression is reduced in multiple long-lived conditions, and...

Aging is a major contributor to the escalating prevalence of heart failure (HF). Ferroptosis has been implicated in age-related disorders and cardiovascular diseases. The role of ferroptosis in age-related HF remains unclear. Here, we show that aged rats exhibit impaired cardiac function accompanied by hallmark features of ferroptosis, including reduced glutathione peroxidase 4 (GPX4) expression and excessive lipid peroxidation. Consistently, cardiomyocyte-specific GPX4 knockout mice develop...

Cancer is associated with biological aging and functional decline; however, few studies have simultaneously examined objective changes in physical function and biological aging in older adults who develop cancer. We therefore compared functional and accelerated aging in generally healthy adults with and without incident invasive cancer, using data from DO-HEALTH, a three-year, randomized controlled trial including 2152 participants (mean age: 74.9 years, 61.1% women), free of major health...

Frailty is a modifiable aging-related condition driven by chronic inflammation and metabolic dysregulation, which are influenced by diet. Metabolomic profiling captures individual metabolic responses and can uncover mechanisms linking diet to frailty. This study examined the effects of food-derived metabolites on changes in frailty risk, both directly and through inflammatory pathways. This longitudinal study included baseline and three-year follow-up data from 9992 participants aged 45-85 years...

Older age combined with chronic disease increases the risk of malnutrition and frailty, impacting disease recovery and overall clinical outcomes. Serum concentrations of several trace elements and their respective biomarkers have not yet been investigated with regard to frailty in older adults with disease, although these patients most likely have an altered trace element profile owing to both inflammatory conditions and inadequate dietary intake. This cross-sectional study investigated trace...

Haematopoiesis has long been a paradigm for understanding how human genetic variation can influence physiology in health and disease, ranging from the genetic characterization of Mendelian blood diseases to population-scale genomic studies of blood cell phenotypes and diseases. More recently, advances in single-cell genomics and variant-to-function mapping are enabling mechanistic insights into how genetic variation shapes blood cell development. Alongside inherited variation, the...

How minute pathogenic signals trigger decisive immune responses is a fundamental question in biology. Classical signaling often relies on ATP-driven enzymatic cascades, but innate immunity frequently employs death fold domain (DFD) self-assembly. The energetic basis of this assembly is unknown. Here, we show that specific DFDs function as energy reservoirs through metastable supersaturation. Characterizing all 109 human DFDs, we identified sequence-encoded nucleation barriers specifically in the...

Age-related cellular changes negatively impact CD4^(+) T cell function. Our prior work showed that mitochondrial complex II (succinate dehydrogenase [SDH]) expression was upregulated in T cells from older (O) adults (60-80 years old). T cells from older adults also produced higher amounts of cytokines generally considered proinflammatory, such as Th17 cytokines IL-17A/F and IL-21, and the Th-17-supportive cytokine IL-6, compared to T cells from younger (Y) adults (25-40 years old). The objective...

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The question of whether aging should be classified as a disease has gained prominence in geroscience, fueled by advances in molecular biology and the aspiration to develop interventions that mitigate age-associated functional decline. However, evolutionary models describe aging as an emergent consequence of declining selection gradients and life-history trade-offs rather than as a deviation from species-typical function. Comparative data across taxa reveal substantial heterogeneity in aging...

Postural control is expressed as intermittent organization of center-of-pressure (CoP) motion on a saddle-shaped manifold typically aligned with the anteroposterior (AP) and mediolateral (ML) axes. When task demands reorient postural focus, this saddle rotates away from the AP-ML alignment yet preserves orthogonal axes that indicate directions of greatest and least fractal temporal correlations in sway. Preserved orthogonality appears to reflect a balance between endogenous fractal fluctuations...