Aging & Longevity

Supplementation with ubiquinol 10 has been shown to improve the health of experimental animals and elderly individuals. The present study investigated the effects of lifetime supplementation with ubiquinol 10 on the progression of aging and lifespan in C57BL/6 mice, a standard strain for biomedical and aging research. A diet containing ubiquinol 10 (0.3 % w/w) and a control diet were fed to female C57BL/6J mice from 8 weeks of age until death, and the progression of senescence, lifespan, and...

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Mutations in the Lamin A (LMNA) gene, which encodes the Lamin A and C proteins, cause severe human diseases collectively known as laminopathies. These conditions are often devastating and lack effective therapies. In this study, we developed precise base editing (BE) strategies targeting the human LMNA gene variants L35P and R249Q, which cause congenital muscular dystrophy (CMD) and dilated cardiomyopathy with conduction defects (DCM-CD), respectively. Induced pluripotent stem cell-derived...

As Alzheimer's disease (AD) is diagnosed more frequently in women, understanding the role of sex has become a key priority in AD research. However, despite aging being the primary risk factor for AD, it remains unclear whether men and women differ in the extent of brain decline with age. Using 12,638 longitudinal brain MRIs from 4,726 participants aged 17 to 95 y across 14 cohorts, we examined sex differences in structural brain changes over time, controlling for differences in head size. Men...

Animals can typically maximize their fitness by reproducing throughout adulthood. Yet, in a handful of species, females cease reproduction long before death, highlighting an apparent evolutionary paradox. We used over three decades of life-history and behavioral data to examine the prevalence of postreproductive lifespan in wild mountain gorillas (Gorilla beringei beringei). Almost one third of females in our study population (7/25) have been "postreproductive" according to a commonly used...

Aging is a major risk factor for neurodegenerative diseases, yet the role of senescent microglia in age-related cognitive dysfunction remains incompletely understood. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been extensively studied for their significant potential in anti-aging. In this study, we demonstrated that hUC-MSCs ameliorate age-related cognitive decline and downregulate senescence-associated markers in the aged hippocampus. Furthermore, co-culture experiments...

CONCLUSION: This study comprehensively reviews current research status, hotspots and trends of NIBS in AD. The results suggest that researchers should focus on the cognitive impact of NIBS technology on AD patients, the best therapeutic targets and potential mechanisms. Strengthening global collaboration among international, institutional and scientific researchers should be promoted to promote the in-depth development of this field.

INTRODUCTION: Aging is a normal process causing deterioration in normal brain function and is inevitable. The aging process is described by the buildup of senescent cells and a decline in the ability to maintain essential homeostatic functions. Cellular aging represents a critical process where cells undergo cell cycle arrest in response to stress and neuronal damage. Many neurodegenerative disorders are closely linked to cellular senescence caused by oxidative stress, ROS generation, and DNA...

Current knowledge regarding the role of gut microbiota (GM) dysbiosis and biological aging in the pathogenesis of age-related macular degeneration (AMD) remains limited. This study aims to explore the causal relationships among these factors in AMD development. Utilizing two-sample bidirectional mendelian randomization (MR), we analyzed genome-wide association study (GWAS) data from 105,248 individuals, including 14,034 early AMD cases, to assess causality between AMD, GM taxa, and biological...

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...

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,...