Approach toward age-related diseases with the use of a new senolytic drugs
Description: Although cellular senescence acts primarily as a tumor suppression mechanism, the accumulation of senescent cells in vivo eventually exerts deleterious side effects due to inflammatory and/ or tumor-promoting factor secretion. Thus, the development of new drugs that specifically eliminate senescent cells, termed senolysis, is anticipated. In this study, I found that ARV825, which was identified as a promising senolytic drugs in my lab, provokes senolysis due to two independent but integrated pathways: (i) attenuation of non-homologous end joining repair, and (ii) up-regulation of autophagic gene expression. Notably, the elimination of chemotherapy-induced senescent cells by a ARV825 substantially increased the efficacy of chemotherapy against xenograft tumor in immunocompromised mice. These results reveal the vulnerability of senescent cells and open up the possibilities for its control.
Amount: ¥4,290,000
Funding type: fellowship
Funder scheme: Grant-in-Aid for Early-Career Scientists
Start date: 2018-04-01
End date: 2020-03-31
Investigator: Masahiro Wakita
Institution: Osaka University
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Funded outputs count: 3
Funder award ID: 18K15065
OpenAlex ID: G2270710732