bims-minfam 2025-10-26 papers

Nat Aging. 2025 Oct 24.

Joint Bone Spine. 2025 Oct 21. pii: S1297-319X(25)00155-1. [Epub ahead of print] 105993

Connecting the Dots: Gouty Arthritis, Clonal Haematopoiesis and Myeloid Activation, in a Unified Inflammation Model for Atherosclerosis Progression.

Faith Inkum, Xiaoxiao Geng, Robert Terkeltaub, Isidoro Cobo.

Gout, one of the most prevalent inflammatory arthropathies, arises from hyperuricemia and is increasingly recognized as a condition extending beyond the joints. Hyperuricemia, the core risk factor for gout, is also an independent risk factor for cardiovascular disease (CVD), complications, and mortality. Multiple conditions that predispose to gout and hyperuricemia, including obesity, metabolic syndrome, type 2 diabetes, hypertension, and chronic kidney disease (CKD), also elevate the risk of atherosclerosis, the central contributor to CVD and the leading cause of mortality in Western societies. The association between gout and atherosclerosis highlights the need for deeper understanding of causal links between these conditions. Because evidence remains insufficient to support urate-lowering therapies for improving cardiovascular outcomes, attention has shifted to other mechanisms connecting gout and atherosclerosis. Given the lack of convincing data for clinically significant monosodium urate crystal (MSUc) deposition in atherosclerotic plaques, this review focuses on the hypothesis that expansion of local articular to systemic inflammation, driven by macrophage activation by MSUc, is the primary mechanism accelerating atherosclerosis in gout. Mechanistically, we explore how epigenetic regulators normally restrain MSU-induced local inflammation, thereby protecting against atherosclerosis. We further discuss how aging-related somatic mutations in genes involved in clonal hematopoiesis of indeterminate potential (CHIP) disrupt this protection, resulting in heightened systemic inflammation and atherosclerosis in patients with gout.

Keywords: CHIP; DNMT3A; Gout; TET2; atherosclerosis; macrophages; monocytes

DOI: https://doi.org/10.1016/j.jbspin.2025.105993

Extracell Vesicles Circ Nucl Acids. 2025 ;6(3): 594-608

Stem-cell-derived extracellular vesicles in neurodegeneration and neuroaging: therapeutic potential and challenges.

Mohit Kumar, Sudipta Ray, Susmita Sil.

Neuroaging is a complex biological process in which the brain undergoes progressive functional decline marked by synaptic loss, neuroinflammation, and cognitive decline. At the molecular and cellular level, aging is driven by multiple interconnected hallmarks, including genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, cellular senescence, stem cell exhaustion, and altered intercellular communication. Among these, cellular senescence, a state of irreversible cell cycle arrest, has emerged as a critical contributor to brain aging. Senescent cells accumulate with age, driven by the p53-p21 and p16-pRb pathways, and secrete pro-inflammatory factors via senescence-associated secretory phenotype (SASP), thereby exacerbating neurodegeneration, vascular dysfunction, and cognitive decline. Extracellular vesicles (EVs) are natural nanocarriers of proteins, lipids, and nucleic acids, and have emerged as key mediators of intercellular communication and therapeutics for aging and age-related conditions. EVs derived from various cell types, such as mesenchymal stem cells (MSCs), neural stem cells (NSCs), and induced pluripotent stem cells (iPSCs), can modulate senescence-related pathways, reduce inflammation, and promote tissue repair. Preclinical studies demonstrate that stem-cell-derived EVs can improve cognitive performance, enhance neurogenesis, reduce senescence phenotype, improve neuronal survival through neuroprotective miRNAs (miR-181a-2-3p), suppress neuroinflammation via inhibition of NLRP3 inflammasome, and support synaptic plasticity. Stem cell EVs possess natural biocompatibility, the ability to cross the blood-brain barrier (BBB), and targeted delivery mechanisms, making them promising candidates for anti-aging interventions. This review elaborates on the multifaceted role of stem cell EVs in mitigating brain aging, senescence, and age-associated chronic disease phenotype.

Keywords: Brain aging; extracellular vesicles; neurodegeneration; stem cell therapy

DOI: https://doi.org/10.20517/evcna.2025.65

Gerontology. 2025 Oct 24. 1-6

Healthy aging at moderate altitudes.

Annalisa Cogo, Benjamin D Levine, Martin Burtscher.

DOI: https://doi.org/10.1159/000549062

Nature. 2025 Oct 22.

People with some cancers live longer after a COVID vaccine.

Max Kozlov.

Keywords: Cancer; Immunology; Medical research; SARS-CoV-2

DOI: https://doi.org/10.1038/d41586-025-03432-7

Biogerontology. 2025 Oct 21. 26(6): 194

Obstructive sleep apnea and aging of the cardiovascular system: a multidimensional analysis of the mechanisms involved.

Xiaolin Hao, Yan Li, Xiaoling Gao.

Emerging evidence has revealed a strong association between obstructive sleep apnea (OSA) and aging. Considering the critical role of the cardiovascular system, this review explores the key mechanisms linking OSA to cardiovascular aging through a focus on chronic intermittent hypoxia (CIH) -induced oxidative stress and chronic inflammation. Specifically, we examine six key pathways: (1) cellular senescence, (2) mitochondrial dysfunction, (3) metabolic dysregulation, (4) telomere attrition, (5) impaired intercellular communication, and (6) adipose tissue senescence. These insights provide a foundation for identifying novel interventions and therapeutic targets to mitigate or even reverse cardiovascular aging.

Keywords: Adipose tissue senescence; Cardiovascular system aging; Metabolic dysregulation; Mitochondrial dysfunction; Obstructive sleep apnea

DOI: https://doi.org/10.1007/s10522-025-10337-5

J Clin Med Res. 2025 Oct;17(9): 469-489

Adenosine Monophosphate-Activated Protein Kinase Activation and Mammalian Target of Rapamycin Complex 1 Inhibition: A Mechanistic Rationale for Anti-Aging Therapy in Type 2 Diabetes.

Hidekatsu Yanai, Hiroki Adachi, Mariko Hakoshima, Hisayuki Katsuyama.

Aging is a complicated biological process that induces a decline in the human organs' structure and function and elevates the risks of aging-related diseases such as Alzheimer's disease (AD) and type 2 diabetes. Type 2 diabetes accelerates all clinical manifestations of aging. Metabolic disorders in type 2 diabetes are unfavorably associated with all hallmarks of aging, such as inflammation and mitochondrial dysfunction. Adenosine monophosphate-activated protein kinase (AMPK) and the mammalian target of rapamycin complex 1 (mTORC1) are key players in cellular metabolism, and AMPK activation and mTORC1 inhibition improve all hallmarks of aging. AMPK activation and mTORC1 inhibition are favorably associated with diabetic complications. Nutritional interventions, such as caloric restriction, resveratrol, and astaxanthin, have AMPK-activating and mTORC1-inhibitory effects and improve metabolic abnormalities in type 2 diabetes. Anti-diabetic drugs, metformin, sodium-glucose cotransporter-2 inhibitors, and glucagon-like peptide 1 receptor agonists have been reported to have AMPK-activating and mTORC1-inhibiting effects and show prevention of aging-related diseases such as cardiovascular disease. The therapeutic interventions that activate AMPK and inhibit mTORC1 may be optimal treatments for type 2 diabetes from the perspective of anti-aging medicine. Furthermore, senolytics may be a promising, direct anti-aging therapeutic strategy specifically for type 2 diabetes and its complications.

Keywords: AMP-activated protein kinase; Aging; Mammalian target of rapamycin complex 1; Metformin; Type 2 diabetes

DOI: https://doi.org/10.14740/jocmr6370

J Am Geriatr Soc. 2025 Oct 22.

Characterization of National Institute on Aging-Funded Clinical Trials for Alzheimer's Disease.

Kavya M Shah, Bhav Jain, Abhinav Komanduri, Sravya Kuchibhotla, Urvish Jain, Rishi M Shah, Kevin A Schulman.

Keywords: Alzheimer's disease; National Institute on Aging; clinical trials

DOI: https://doi.org/10.1111/jgs.70185