Cellular senescence: Implications for metabolic disease

Abstract

The growing burden of obesity- and aging-related diseases has hastened the search for governing biological processes. Cellular senescence is a stress-induced state of stable growth arrest strongly associated with aging that is aberrantly activated by obesity. The transition of a cell to a senescent state is demarcated by an array of phenotypic markers, and leveraging their context-dependent presentation is essential for determining the influence of senescent cells on tissue pathogenesis. Biomarkers of senescent cells have been identified in tissues that contribute to metabolic disease, including fat, liver, skeletal muscle, pancreata, and cardiovascular tissue, suggesting that pharmacological and behavioral interventions that alter their abundance and/or behavior may be a novel therapeutic strategy. However, contradictory findings with regard to a protective versus deleterious role of senescent cells in certain contexts emphasize the need for additional studies to uncover the complex interplay that defines multi-organ disease processes associated with obesity and aging.

Targeted Reduction of Senescent Cell Burden Alleviates Focal Radiotherapy-Related Bone Loss

“…Individually, D, Q, and F function as senolytic drugs (serving to kill senescent cells) . F and D+Q improve health span by reducing senescent cell burden . D+Q has also been shown to alleviate age‐related bone loss in mice .…”

AMP-activated protein kinase: the current landscape for drug development

“…Indeed, metformin increases AMPK and mitochondrial function in multiple tissues, effects that are associated with reductions in oxidative damage, chronic low-grade inflammation and improved health span and lifespan in mice 318 . The AMPK activator quercetin when used in combination with dasatinib has also been shown to exert anti-ageing effects by delaying senescent cell accumulation or reducing senescent cell burden in numerous tissues of rodents 326 . Whether these beneficial effects are replicated in humans and/or are observed with the new generation of direct AMPK activators that do not inhibit mitochondrial function remains to be determined.…”

Inflammation and Premature Ageing in Chronic Kidney Disease

“…Obesity is a major predictor contributing to type 2 diabetes (T2D), CKD, CVD, and increased mortality [135,136]. Besides being risk factors for CKD, obesity and T2D also contribute to cellular senescence per se [137,138]. Furthermore, the adverse effects of an increased fat mass are at least partly related to the secretion of proteins from adipocytes into the circulation, that is, adipocytokines.…”