Senotherapy, cancer, and aging

Abstract

Introduction: We aimed to highlight the effects of senotherapy on the prevention and treatment of cancer in older individuals. The aim of senotherapy is to eliminate senescent cells. These cells express the senescence-associated secretory phenotype (SASP). With production of inflammatory cytokines, growth factors, and different type of proteases, the SASP is responsible for aging-associated disability and diseases. All mammalian cells experience senescence. The main agents of aging include fibroblasts and adipose cells. Senescent tumor cells may undergo genomic reprogramming and re-enter cell cycle with a stem cell phenotype.

Materials and methods: We conducted a Medline search for the following key words: senotherapy, senolysis, senomorphic agents. We provide a narrative review of the finding.

Results: Different agents may eliminate senescent cells from cell cultures and murine models. These include metformin, rapamycin, desatinib, quercitin, fisetin, ruloxitinib, and BCL2 inhibitors. A randomized controlled study of metformin in 3,000 patients aged 65-79 without glucose intolerance aiming to establish whether senotherapy may prevent or reverse disability and aging associated diseases, including cancer, is ongoing. Senotherapy prolongs the life span and decreases the incidence of cancer in experimental animal models, as well as delays and reverses disability. Senescent tumor cells are found prior to treatment and after chemotherapy and radiation. These elements may be responsible for tumor recurrence and treatment refractoriness.

Discussion: Senotherapy may have substantial effects on cancer management including decreased incidence and aggressiveness of cancer, improved tolerance of antineoplastic treatment, and prevention of relapse after primary treatment. Senotherapy may ameliorate several complications of cancer chemotherapy.

Keywords: Cancer in the older patient; Chemotherapy; Senolysis; Senomorphic therapy; Senotherapy.