Aging & Longevity

An established vascular network is a prerequisite to ensuring an optimal supply of oxygen and nutrients for sustaining developmental events and systemic function. Herein, we construct a time-resolved proteolipidomic atlas of the aorta across the human life cycle. trans-omics integration reveals that postnatal ganglioside GM3 accumulation is functionally coregulated with calcium homeostasis mediated by plasma membrane calcium-transporting ATPases (PMCAs). We then verify mechanistically in...

Extracellular matrix degradation is a fundamental pathological feature of osteoarthritis, while the roles of degraded matrix remain largely unknown. We previously showed that serum elastin fragments were a systemic aging driver. Here, we found that elastin fragments were upregulated in synovial fluid in dual-center osteoarthritis patients. Elastin fragments actively impaired joint tissue in mice and human explants. Mechanistically, a specific elastin motif containing...

Sleep deprivation (SD), together with inevitable stress inherent to conventional SD protocols, can induce oxidative stress and inflammation, thereby increasing the risk of premature death. However, the source and signaling pathways underlying reactive oxygen species (ROS) generation remain unclear. Here, we demonstrate that both mechanical and thermogenetic SD, along with possible stress induced by both protocols, lead to initial ROS accumulation in Drosophila gut subregions, including the...

Roman concrete structures have remained serviceable for nearly two millennia and are widely regarded as outstanding examples of durable ancient engineering. Existing literature attributes Roman concrete longevity to the pozzolanic reaction that occurs between reactive volcanic ashes and lime. While the pozzolanic reaction is of fundamental importance, we argue that carbonation over a long period of time also substantially enhances the durability and potential self-healing properties of concrete....

Cellular senescence has emerged as a central mechanism driving cutaneous aging, impaired regeneration, and numerous dermatologic pathologies. Initially evolved as a protective mechanism to prevent malignant transformation and facilitate wound repair, senescence becomes maladaptive when senescent cells persist. Senescent keratinocytes, fibroblasts, and melanocytes can secrete pro-inflammatory mediators and other factors, collectively termed the senescence-associated secretory phenotype (SASP),...

Sirtuin 6 (SIRT6) is a protein deacetylase and ribosyltransferase that is a vital hub for maintaining epigenetic homeostasis, regulating the transcriptome, and repairing DNA double stranded breaks (DSBs). Comprehensive proteomic profiling of the SIRT6 posttranslational landscape, however, remains elusive. The SIRT6 C-terminal domain contains multiple phosphorylation sites. We find that the presence and the use of these sites are strongly correlated with maximum lifespan across mammals....

Late-life depressive symptoms have been associated with structural brain changes and cognitive impairment, but prior studies have typically examined individual markers of brain aging in isolation. This study examined the associations between depressive symptoms and multiple markers of brain aging in a population-based cohort of community-dwelling older adults. Baseline data from 2,746 participants with complete data on depressive symptoms, neuroimaging measures, cognitive assessment, and...

Cognitive impairment is highly prevalent among patients with end-stage renal disease (ESRD), particularly those undergoing dialysis, and is associated with poor clinical outcomes and reduced quality of life. Emerging evidence suggests that Klotho, an anti-aging protein predominantly expressed in the kidney, plays a critical role in the pathophysiology of uremia-related cognitive dysfunction. This review summarizes current clinical and experimental evidence regarding Klotho deficiency in dialysis...

Fibroblast growth factor 21 (FGF21) is a stress-induced endocrine hormone that regulates metabolism. Grandl et al. show that FGF21, through its receptor β-klotho (KLB), enhances sulfide signaling and hydrogen sulfide production, strengthening the unfolded protein response and integrated stress response to promote stress resilience, metabolic adaptation, and potentially healthy aging.

The stomach harbors a complex microbial niche, yet the persistence and disease relevance of its core microbiota remain unclear. Using full-length 16S and ITS sequencing of 255 pediatric samples, this study identifies 11 core bacterial genera organized into two antagonistic communities, CST1A and CST1B. CST1A is enriched in non-ulcer controls, whereas CST1B is associated with gastroduodenal disease, with limited fungal involvement. Stratified analyses show that Helicobacter pylori infection...

Dietary strategies that support long-term cognitive health and resilience against neurodegenerative diseases are important with aging and senescence. Brain aging is a consequence of intricate biological changes that occur over the lifespan. The process of aging involves the decline in metabolic and physiologic functions, and changes in anatomical structure. However, our lifestyle practices, including diets and nutrient intakes, physical exercise, sleep quality, and cognitive activity can help to...

Vascular aging is a fundamental contributor to the development of chronic diseases and has emerged as a critical focus in biomedical research. With the rapid advancement of artificial intelligence (AI), new opportunities have arisen to enhance the precision and efficiency of vascular aging studies. AI techniques, particularly those applied to large-scale multi-omics and medical imaging data, enable the identification of novel biomarkers and the development of robust models to quantify the rate...

Lactate was long considered a waste metabolic byproduct. Currently, lactate functions as an energy substrate, signaling molecule, and epigenetic regulator in the central nervous system (CNS). Lysine lactylation (Kla), a novel lactate-dependent PTM, acts as a core epi-metabolic mediator by directly linking cellular metabolism to epigenetic remodeling. This review summarizes lactate production, shuttling, and the regulatory mechanism of lactylation (donors, writers, erasers, readers). We outline...

Adult hippocampal neurogenesis is essential for learning, memory, and mood regulation, and its disruption is implicated in ageing, neurodegeneration, and mood disorders. However, the mechanisms linking inflammation to adult hippocampal neurogenesis impairment remain unclear. Here, we identify chronic tumour necrosis factor-alpha signalling as a key driver of neurogenic dysregulation via a previously unrecognised type I interferon autocrine/paracrine loop in human hippocampal progenitor cells....

Enzyme immobilization is pivotal to sustainable biocatalysis, yet the most widespread protocol of physical adsorption on static porous supports suffers from enzyme leakage and short catalytic lifespan. We introduce a dynamic-pore mechano-locking strategy employing tetrafluoroazobenzene-engineered covalent organic frameworks (COFs), where visible-light-mediated isomerization enables precise and reversible pore-size variation for adaptive enzyme confinement. This approach significantly enhances...

No abstract

CONCLUSION: COPD is an important risk factor for the occurrence and persistence of frailty in older adults. Anti-inflammatory diets may provide independent protection against persistent frailty and might attenuate the adverse impact of COPD on persistent frailty risk, though further direct comparative analyses are warranted. It is recommended to incorporate anti-inflammatory diet intervention into the comprehensive management plan for COPD patients to reduce the risk of frailty occurrence and...

CONCLUSIONS: Community-dwelling older adults showed distinct psychosocial and cognitive profiles that were differentially associated with health-related quality of life and healthy aging. Healthy aging was most favorable in the group characterized by limited social network resources but high perceived social support, low depressive symptoms, and favorable subjective cognitive function. These findings suggest that healthy aging may depend not only on social network resources, but also on...

Mitochondrial decline is a hallmark of ageing, yet the role of intergenomic compatibility in shaping ageing trajectories remains poorly understood, particularly in an ecologically relevant framework. Hormetic interventions have been proposed as strategies to modulate metabolism and lifespan, but it is unknown how this operates in the context of mitonuclear discordance. Here, we demonstrate that mitonuclear mismatch accelerates age-related mitochondrial decline, elevates reactive oxygen species...

Synaptic transmission can be tuned through plasticity mechanisms that regulate synaptic strength, structure, and number. In vivo measurements demonstrate remarkable spine dynamics, with subsets of synapses persisting for months. This correlates with the longevity of certain memories, which can persist for an organism's lifetime. The molecular basis supporting the long-term stability of specific synapses and the long-term durability of memories remains unknown. At the protein level, most proteins...