Aging & Longevity

Aging is a complex multifactorial process that affects cellular function and tissue homeostasis over time. Despite substantial research, the molecular mechanisms driving cellular aging remain poorly understood. Many studies focused on changes in DNA methylation as an indicator of aging. In particular, methylation at polycomb CpG islands was shown to be predictive of phenotypic changes associated with aging. Since many age-related pathological processes are thought to originate from single cells,...

Aging is accompanied by progressive physiological decline and an increased risk of chronic disease, motivating the search for interventions that promote healthy longevity. We found that mid-life administration of Corylin, a flavonoid derived from Psoralea corylifolia, improves metabolic function, muscle integrity, and physical performance in mice maintained on a standard diet. Corylin significantly extends median lifespan in female mice, with an 11.9% increase and a 33% higher survival rate at...

Chronic inflammation drives vascular aging and stroke risk, yet circulating proteins linking immune activation to cerebrovascular events remain elusive. People with HIV (PWH) face elevated stroke risk beyond traditional vascular risk factors, even under antiretroviral therapy. We aimed to identify circulating proteomic signatures of HIV-associated stroke, characterize underlying biological pathways, and assess their longitudinal stability. We conducted a nested case-control study of 135 PWH with...

Different species age in similar ways but their lifespans differ by orders of magnitude. It is not clear how these similarities and differences arise from the accumulation of damage that underlies aging. Does long lifespan arise from reduced damage production, increased removal or enhanced robustness to damage? Here we apply the saturating removal model-a stochastic model of damage accumulation and removal-and fit it to survival data from well-studied species. Several parameters have...

How the small intestine ages at the cellular and molecular level has been unclear. Here we profile single nuclei from young and aged primate small intestine and find that aging brings barrier dysfunction, chronic inflammation and a shift in stem cell differentiation away from absorptive cells toward secretory cells. Through integrative multimodal analysis, we identify the transcriptional corepressor NCoR1 as a key player whose decline is conserved in the aging human gut. In human intestinal...

Nucleotides-essential substrates for DNA repair, energy metabolism, and redox regulation-are emerging as nutritional modulators of biological aging. Yet, individual responses to exogenous nucleotide (NTs) supplementation remain poorly understood. Given that urate metabolism governs systemic oxidative balance, this study investigated whether genetic variability in urate regulation modifies the anti-aging effects of NTs. In this secondary analysis of the TALENTs randomized controlled trial (121...

Aging reshapes global disease burdens, yet the regulatory roles of long non-coding RNAs (lncRNAs) in age-related disorders remain incompletely characterized. We developed iLDA-SGCN, a graph-based computational framework that integrates singular value decomposition (SVD) with dual graph convolutional networks (GCNs) to predict lncRNA-disease associations. SVD first derives compact low-dimensional representations from the lncRNA-disease association matrix. Two complementary GCN modules then learn...

Excessive alcohol consumption poses significant health risks and is closely associated with oxidative damage. The KEAP1-NRF2-ARE signaling pathway serves as the primary antioxidant system. However, current small molecule inhibitors are all covalently bound to KEAP1, meaning that once bound, they are not easily dissociated, while continuous inhibition of KEAP1 exhibits severe side effects. In this study, BLI, CETSA, Pull-down, Co-IP, and HDX-MS assay analysis were conducted to detect the KEAP1...

CONCLUSIONS: Maintaining favorable long-term patterns of PA, even with gradual decline, is associated with reduced odds of DS among older adults with chronic diseases. These findings support PA as a potentially cost-effective strategy for secondary prevention and highlight the importance of sustained behavioral patterns in mitigating mental health risks in aging populations.

CONCLUSION: Frailty is common among Iranian older adults and is independently associated with poorer physical QoL and, to a lesser extent, mental QoL. These findings support the need for targeted screening and multidomain interventions.

Neurons and glia work together to dynamically regulate neural circuit assembly and maintenance. In this study, we show that Drosophila exhibit large-scale synapse formation and elimination as part of normal CNS circuit maturation and that glia use conserved molecules to regulate these processes. Using a high-throughput ELISA-based in vivo screening assay, we identify new glial genes that regulate synapse numbers in Drosophila in vivo, including the scavenger receptor ortholog Croquemort (Crq)....

Osteoporosis, a common metabolic bone disorder linked to aging, is often accompanied by muscle degeneration. Muscle Bmal1 disruption in mice has been shown to affect various tissues, including the kidney, lung, and bone, indicating that the muscle molecular clock may influence the physiological homeostasis of multiple organs through systemic circulation. Despite this, the role of the muscle clock in age-related osteoporosis remains unclear. In aged mice, we observed a disruption in the circadian...

Lead exposure remains a significant public health problem, and even within current standards, most individuals have limited means to avoid it. Regulating or removing toxic exposures remains a priority, but complementary nearer-term protections are needed. We previously observed that health insurance coverage attenuated associations of blood lead levels with two DNA methylation-based biomarkers of morbidity and mortality: GrimAge2 and DunedinPoAm. In this study, we evaluated whether healthcare...

Exposure to low levels of environmental challenges, known as hormetic stress, fosters subsequent stress resistance and promotes healthy aging in later life. However, specific mechanisms governing transcriptional reprogramming upon hormetic nutrient stress remain elusive. Here, we identify histone H3 lysine 27 acetylation (H3K27ac) as a crucial driver of transcriptomic adaptation to hormetic fasting. Beyond its immediate function of enhancing lipid catabolism for alternative energy sources,...

CONCLUSION: The updated Brazilian Portuguese version of the CFS demonstrates excellent reproducibility and strong convergent validity in hospitalized older adults. These results support its use as a reliable clinical and research tool for frailty assessment in hospitalized older adults, within the scope of the measurement properties evaluated.

Brain aging is increasingly recognized as a heterogeneous and systems-level process involving dynamic interactions among neuronal, glial, vascular, and immune-associated cell populations. Recent advances in single-cell and spatial omics technologies have revealed diverse cellular aging trajectories, region-specific vulnerabilities, and extensive remodeling of intercellular communication networks across the aging brain. These findings challenge reductionist views of aging and emphasize the...

[This corrects the article DOI: 10.3389/fnagi.2026.1707228.].

The aging bone marrow microenvironment is characterized by chronic low-grade inflammation ("inflammaging"), which disrupts skeletal homeostasis and impairs bone regeneration. However, the stromal-immune crosstalk mechanisms sustaining this pathological state remain poorly defined. Here, transcriptomic analysis identified thrombospondin-1 (Thbs1) as a key upregulated component of the senescence-associated secretory phenotype (SASP) in aged bone mesenchymal stromal cells (BMSCs). We demonstrate...

Kaempferol (KMP) is a dietary compound found in a wide range of foods. The therapeutic capabilities of these foods are associated with the phenolic compounds present in their structures, particularly their antioxidant activity. Remarkable medical care areas linked to KMP include pain relief, anti-aging, antiallergic, anticancer, antidiabetic, anti-inflammatory, antioxidant, antipyretic, central nervous system regulation, wound healing, and hepatoprotective characteristics. KMP has attracted...

Age-related decline in speech perception is a prominent challenge in auditory aging, especially under noise conditions. However, how neural and neurovascular processes are jointly organized and coordinated across adulthood during speech perception remains incompletely characterized. This study employed simultaneous electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS) to investigate neural activation, functional connectivity, and neurovascular coupling across youth (n =...