Aging & Longevity

INTRODUCTION: Gait alterations have been proposed as functional indicators of neural dysfunction in Alzheimer's disease; however, their ability to capture disease-associated locomotor changes in preclinical models remains insufficiently characterized.

As organisms age, mitochondrial metabolic activity declines, and disrupted gene expression regulation mediated by histone acetylation induces the emergence of senescent physiological phenotypes in tissues. In this study, we found that periodic exposure to red light significantly increased histone H3 Lys9 acetylation (H3K9ac) levels in the tissues and organs of aged mice. Following red light exposure, silent information regulation factor 4 (SIRT4) protein levels in keratinocytes were notably...

Cellular quiescence is a low metabolic, non-proliferative state critical for tissue maintenance and regenerative capacity, with broad implications for aging and age-related diseases. In Caenorhabditis elegans, L1 developmental arrest upon hatching in the absence of food provides a robust in vivo model to study quiescence. Here, we investigate the roles of the transcription factors HLH-30/TFEB and DAF-16/FOXO during L1 arrest. We show that HLH-30 and DAF-16 collaborate to ensure survival under...

Proteostasis is essential for cellular health, with its disruption contributing to aging, neurodegeneration, and metabolic disorders. While the upstream proteotoxic stress-sensing and protein-folding mechanisms in the ER and cytosol are well studied, the transcriptional regulation of proteostasis remains incompletely understood, particularly concerning the temporal epigenome dynamics, chromatin landscapes, and co-regulatory networks underlying dynamic proteostasis control. Traditionally,...

The DNA damage response (DDR) pathway has emerged as the central signaling network that preserves genome stability by using sensors to monitor the genome for aberrant structures and establishing signaling centers that promote organismal homeostasis. This review revisits the formative years of DDR research, focusing on the genetic dissection of the pathway in Saccharomyces cerevisiae and its evolution into a broadly conserved eukaryotic signaling system. Early studies of ribonucleotide reductase...

The extraordinary lifespan variation in domestic dogs provides a natural experiment for testing how intrinsic rates of biological aging shape lifespan. Using 1640 methylomes from 894 dogs, we developed an epigenetic clock that predicted mortality and demonstrated that epigenetic aging is fastest early in life. At orthologs of human age-associated genes, dogs exhibited concordant age effects on promoter methylation, highlighting conserved remodeling of immune pathways. We found that larger and...

Time-restricted feeding (TRF) restricts food intake to daily windows, yet its efficacy against vascular aging and underlying mechanisms remain unclear. Here, we demonstrate that TRF attenuates angiotension II -induced accelerated vascular aging by reshaping gut microbiota, stabilizing microbial diversity, and elevating the Firmicutes/Bacteroidetes ratio. TRF preserved intestinal barrier integrity, upregulated tight junction proteins (Occludin, ZO-1, MUC2), reduced serum lipopolysaccharide, and...

Aging-associated β-cell senescence is a key driver of type 2 diabetes mellitus (T2DM). However, its associated molecular mechanisms remain poorly explored. This study identifies Chromobox 4 (CBX4), a Polycomb group protein with SUMO E3 ligase activity, as an essential regulator of β-cell aging and function. The results show that CBX4 expression progressively downregulates in both aged and diabetic pancreatic islets. Targeted deletion of Cbx4 in β-cell accelerates cellular senescence, impairs...

The pursuit of high-energy-density lithium metal batteries is often hampered by severe safety hazards and limited cycle life, leading to increased environmental impact and higher costs. Here, we demonstrate that tuning the underappreciated miscibility between electrolyte components could provide an effective approach. By introducing a non-coordinating, non-flammable cyclic fluorinated diluent, we minimize diluent-ion pair intermolecular forces, thereby enabling the formation of isolated...

Black carbon (BC) is a highly toxic air pollutant and potent short-lived climate pollutant. China's Dual Carbon strategy-peaking carbon emissions before 2030 and achieving carbon neutrality before 2060-has driven rapid BC emission reductions. However, global inventories still misrepresent BC emissions in China, biasing estimates of its health and climate impacts. Using a localized BC inventory and revised health risk function, we estimate that over 540,000 premature deaths were attributable to...

The formation of advanced glycation end products (AGEs), first described in food science, is driven by hyperglycaemia (diabetes mellitus) and the modifications on long-lived proteins (natural ageing); AGE formation is enhanced by oxidative stress and inflammation, which are factors that accompany high-AGE settings of diabetes mellitus and ageing. Exogenous tobacco, ultra-processed foods, pollutants and alcohol contribute to AGE formation. Evidence demonstrates higher concentrations of AGEs in...

What is the ultimate goal of biogerontology (the study of the biology of aging)? A fashionable answer these days, often encountered, is that it is to extend healthspan not lifespan. Here we argue that this is a misguided cliché. Experimental research with animal models has demonstrated the possibility of intervening in and retarding the aging process, and extending lifespan. This, to varying degrees, increases both healthspan and gerospan, the later-life phase in diminished health. Considering...

Efficient muscle regeneration relies on the coordinated crosstalk between muscle stem cells (MuSCs) and their surrounding niche. Specialized pro-resolving mediators (SPMs), like resolvins, serve as critical autocrine and paracrine signals within this microenvironment, with macrophages acting as one of the primary sources of SPMs required to resolve inflammation and boost myogenesis. However, while dysregulation of endogenous SPM synthesis in aged skeletal muscle is known to drive chronic...

Research on brain aging has largely focused on neurological disorders such as Alzheimer's disease, mild cognitive impairment, and other forms of cognitive decline. However, relatively few studies have examined how age affects self-knowledge in healthy older adults. Thus, the present study aimed to investigate the impact of age on the neural correlates of self-referential and other-referential processing, as well as patterns of task-related connectivity. To this end, trait adjectives were...

CONCLUSIONS: Consistent with prior autism trait-based research in the general population, middle-aged and older autistic adults report more extensive sleep problems and worse sleep quality than non-autistic adults. Sleep problems were associated with older age and poorer mental health. Though the study is cross-sectional, the findings highlight the need to explore causal links through intervention. Addressing anxiety, and mental health problems more broadly, may improve sleep quality in ageing...

Brain aging provides an integrative marker of systemic health, but whether regional patterns outperform whole-brain approaches remains unknown. Here, we show that regional brain age signatures achieve superior mortality prediction through identifiable neurovascular-immune mechanisms in 1,240 community-dwelling adults followed for 10 years (120 deaths). While global brain age independently predicts mortality (hazard ratio [HR], 1.044 per year), a data-driven three-region model combining the left...

INTRODUCTION: Aging is associated with declines in physical and cognitive capacities, which become more pronounced after age 80. Institutionalization may further increase anxiety and depression. This pilot study assessed the feasibility and effects of a dance intervention on physical function, cognition, and mental health in institutionalized older adults with cognitive impairment.

Aging is accompanied by a decline in circulating ketone bodies and progressive cardiac dysfunction, yet whether dietary ketone repletion counteracts cardiac aging in a sex-specific manner remains unclear. Here, we first investigated the associations between plasma ketone bodies and cardiac function in a human cohort, comprising 120 adults (44.78 ± 10.97 years; 66 male/54 female) and 121 aged individuals (69.59 ± 6.88 years; 75 male/46 female). And, we then evaluated the therapeutic potential of...

CONCLUSIONS: The effects of psychosocial stress-inflammation associations are complex and may depend on cardiovascular burden. Replication is needed to establish temporality and clinical relevance.

White matter hyperintensities (WMH) are ubiquitous on magnetic resonance images (MRI) in older adults. However, the rate and mechanisms of their proliferation remain unclear, as they are inferred mainly from cross-sectional studies and imperfect single indicators of theoretical constructs. To assess the magnitude of WMH change and its modifiers, we conducted a meta-analysis of 54 longitudinal studies. We found the increase in WMH burden over time (pooled effect size) even in the studies with...