Emerging use of senolytics and senomorphics against aging and chronic diseases

Abstract

Senescence is a state of cell cycle arrest that plays an important role in embryogenesis, wound healing and protection against cancer. Senescent cells also accumulate during aging and contribute to the development of age-related disorders and chronic diseases, such as atherosclerosis, type 2 diabetes, osteoarthritis, idiopathic pulmonary fibrosis, and liver disease. Molecules that induce apoptosis of senescent cells, such as dasatinib, quercetin, and fisetin, produce health benefits and extend lifespan in animal models. We describe here the mechanism of action of senolytics and senomorphics, many of which are derived from plants and fungi. We also discuss the possibility of using such compounds to delay aging and treat chronic diseases in humans.

The flavonoid procyanidin C1 has senotherapeutic activity and increases lifespan in mice

“…Under in vitro conditions, GSE suppressed the SASP with maximal efficiency at 0.1875 μg ml −1 (Extended Data Fig. 2a), which fits with the property of senomorphics 24 . Lower or higher concentrations of GSE were less efficacious, perhaps due to the induction of cellular stress responses as a result of increased cytotoxicity (Extended Data Fig.…”

G6PD deficiency, redox homeostasis, and viral infections: implications for SARS-CoV-2 (COVID-19)

“…The mortality rate drops in hospitalized patients with COVID-19 who have received metformin [142,143]. Senolytic drugs reduce inflammation and selectively remove senescent cells during aging [144]. These antiaging compounds can exert their function in promoting healthspan by maintaining redox homeostasis and alleviating oxidative stress [145][146][147].…”

Aging, Cell Senescence, the Pathogenesis and Targeted Therapies of Osteoarthritis

“…Anti-apoptotic and pro-survival pathways are upregulated in SnCs ( Zhu et al, 2015 ). Multiple factors are involved in this pathophysiological process such as BCL-2, BCL-W, and BCL-XL in the BCL-2 protein family, and p53, p21 CIP1 , phosphatidylinositol 3-kinase (PI3K), AKT, FOXO4, tyrosine kinase, and heat shock protein 90 (HSP90) ( von Kobbe, 2019 ; Martel et al, 2020 ). Pro-survival pathways can protect SnCs from their own SASP effect ( Romashkan et al, 2021 ), and these survival networks mainly include PI3K-AKT pathway, BCL-2/BCL-Xl pathway, p53/p21 CIP1 , different kinases, etc.…”