Senotherapy, cancer, and aging

Nov 17, 2023Journal of geriatric oncology

Therapies targeting aging cells in cancer and aging

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Abstract

A randomized controlled study of metformin involving 3,000 patients aged 65-79 is ongoing to evaluate the effects of senotherapy on aging and cancer.

Senotherapy aims to eliminate senescent cells that contribute to aging and cancer through the senescence-associated secretory phenotype (SASP).
Agents like metformin, rapamycin, and several others have shown the ability to remove senescent cells in cell cultures and mouse models.
Senotherapy is associated with prolonged lifespan, reduced cancer incidence, and the ability to delay or reverse disability in experimental animal studies.
Senescent tumor cells can exist before treatment and persist after chemotherapy and radiation, potentially leading to tumor recurrence.
Senotherapy may improve management of cancer by decreasing cancer aggressiveness and enhancing tolerance to anti-cancer treatments.

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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.

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Senotherapy, cancer, and aging

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