Aggregator

Induced pluripotent stem cells (iPSCs) derived from patients with premature aging disorders are widely regarded as a foundation for both the study of fundamental aging mechanisms and preclinical testing of anti-aging therapies. The most well-studied is Hutchinson-Gilford progeria syndrome (HGPS), which is caused by a lamin A gene mutation. Comparing the progeroid phenotype in cell models of distinct premature aging syndromes is critical for identifying early and common aging hallmarks. In this...

Aging is a progressive and complex process of physiological changes that accumulate over time and end up undermining organismal performance. In many cases, this leads to the development of age-related diseases. Therefore, the identification of the exact mechanisms connecting aging to disease will be critical for the advancement of biomedical research in the field. Recently, a growing number of reports have linked ferroptosis, a form of non-apoptotic regulated cell death, to numerous age-related...

Elderly individuals with ulcerative colitis (UC) require specialized care given their prevalent multimorbidity, decreased physiologic reserves, and greater predisposition to adverse outcomes. Therefore, finding safe and effective treatments for this population is crucial. This study investigated whether probiotic mixtures of either Clostridium butyricum and Bifidobacterium infantis (hereinafter designated CB) or VSL#3 (a mixture of eight bacterial species) may reduce the severity of colitis and...

Aging is associated with increased genomic instability, a phenomenon largely driven by the accumulation of DNA damage over time, and large species of mammals seem to have more robust DNA repair systems associated with longer lives. Among DNA lesions, double-strand breaks (DSBs) are particularly deleterious and have been implicated in age-related functional decline and disease. In this study, we investigated how age and body mass affect the efficiency of DSB repair (DSBr) in primary fibroblast...

While preclinical studies suggest that Phosphodiesterase 5 (PDE5) inhibition may reduce cognitive impairment, findings from observational studies on whether PDE5 inhibitors reduce Alzheimer's disease (AD) risk have been inconsistent. We performed a two-sample cis-Mendelian Randomisation (MR) analysis to estimate the causal effect of PDE5 inhibition on AD risk. The analysis was performed across four different genome-wide association studies (GWAS) of AD to enhance reliability through...

The endoplasmic reticulum (ER) stress-response is an adaptive cellular mechanism activated by an accumulation of unfolded proteins within the ER. Although recent evidence shows that the ER stress-response is activated in aged tissues, and therefore ER stress is considered a candidate driver of aging, the spatiotemporal regulation and roles of the ER stress-response during aging remain unclear. To address this research gap, we introduced an Ire1-Xbp1s ER stress-response pathway-sensitive reporter...

Aging is a risk factor for atrial fibrillation (AF). In 19-month-old mice, increases in AF inducibility are associated with enhanced protein levels of fat mass and obesity-associated protein (Fto), and reduced N6-methyladenosine (m6A) modification in atrial tissue. Whether Fto-regulated m6A demethylation is involved in aging-induced AF remains unclear. AF inducibility and electrophysiology were performed through programmed stimulation and optical mapping. The intensities of slow delayed...

Valvular heart disease (VHD) is a highly prevalent age-associated cardiovascular pathology. VHD can be characterised by stenosis, an increase in valve stiffening commonly due to leaflet calcification, or regurgitation, where backflow of blood can occur as a result of valve remodelling. At present, there is a paucity of spontaneous animal models of valve disease which would aid mechanistic investigations and allow therapeutic screening. Here, we report a spontaneously occurring zebrafish valve...

A decrease in osteoblast number and bone formation are seminal contributors to age-related osteoporosis. However, the aging-associated molecular mechanisms that impact osteoblast precursors, osteoblasts, osteocytes, and other bone mesenchymal cell types remain unclear. We performed single-cell RNA-sequencing of mesenchymal cells present at the endosteum and periosteum of young and old C57BL/6 mice of both sexes. Osteoblast precursors and osteoblasts from female endosteum exhibited the greatest...

Many studies have compared gene expression in young and old samples to gain insights on aging, the primary risk factor for most chronic diseases. However, these studies only identify associations without distinguishing drivers of aging from compensatory geroprotective responses or incidental downstream effects. Here, we introduce a workflow to characterize causal effects of differentially expressed genes on lifespan. First, we performed a meta-analysis of 25 gene expression datasets comprising...

Autophagy is intricately linked with protective cellular processes, including mitochondrial function, proteostasis, and cellular senescence. Animal studies have indicated that autophagy becomes dysfunctional with aging and may contribute to T cell immunosenescence. In humans, it remains unclear whether autophagy is impaired in CD4^(+) T cells as people age. To answer this question, we examined basal and inducible autophagic activity in a series of experiments comparing CD4^(+) T cells from...

Immune cell metabolism is increasingly recognized as an important regulator of immune function, but its role in age-related immune dysfunction, chronic inflammation, and cardiometabolic complications in humans remains incompletely understood. This study investigated the impact of aging on monocyte metabolic and functional signatures in a healthy elderly population. We aimed to leverage these immunometabolic signatures to identify healthy elderly individuals with reduced immune cell fitness and,...

Museum specimens collected during a 1907 marine expedition reveal loss of genetic diversity in the Philippines

Joel Mokyr, Philippe Aghion, and Peter Howitt explained why the past 2 centuries have seen sustained economic growth rather than stagnation