Targeting Senescent Cells for a Healthier Aging: Challenges and Opportunities

Abstract

Aging is a physiological decline in both structural homeostasis and functional integrity, progressively affecting organismal health. A major hallmark of aging is the accumulation of senescent cells, which have entered a state of irreversible cell cycle arrest after experiencing inherent or environmental stresses. Although cellular senescence is essential in several physiological events, it plays a detrimental role in a large array of age-related pathologies. Recent biomedical advances in specifically targeting senescent cells to improve healthy aging, or alternatively, postpone natural aging and age-related diseases, a strategy termed senotherapy, have attracted substantial interest in both scientific and medical communities. Challenges for aging research are highlighted and potential avenues that can be leveraged for therapeutic interventions to control aging and age-related disorders in the current era of precision medicine.

Senescence of stromal cells contributes to endometrium dysfunction and embryo implantation failure

“…To this end, we focused on the senomorphics – a class of drugs proved to reduce SASP secretion without affecting viability of senescent cells (Borghesan et al, 2020). We chose two compounds rapamycin and metformin, whose senomorphic activity is well established for various cell types and different models of senescence (Borghesan et al, 2020; Song et al, 2020).…”

“…Today the role of cellular senescence is extensively studied with regard to various pathologies (He & Sharpless, 2017; Borghesan et al, 2020; Karin & Alon, 2021). Promising results in treating diseases of different etiologies have been already obtained based on the senolytics or senomorphics applications, leading either to targeted killing of senescent cells or to reduction of SASP secretion (Song et al, 2020). However, from this point of view, endometrium and female infertility still remain poorly studied, probably, due to several obstacles, which will be discussed below.…”

An Aging-Related Gene Signature-Based Model for Risk Stratification and Prognosis Prediction in Lung Adenocarcinoma

“…Cellular senescence often triggers an immune response in the tumor microenvironment (Song et al, 2020), and immune cell infiltration into the tumor microenvironment promotes tumor growth (Sarode et al, 2020). However, the modulation of immune cells by ARGs is relatively unclear in LUAD.…”

Anti-aging: senolytics or gerostatics (unconventional view)

“…It is expected that rapamycin-like effect may be responsible for the therapeutic effects of senolytics in disease. Some senolytics are investigated for treatment of diseases such as idiopathic pulmonary fibrosis [ 10 , 45 , 149 , 174 ]. Although the treatment of specific diseases is very important, it is a different story entirely.…”