Targeting normal and cancer senescent cells as a strategy of senotherapy

Abstract

Senotherapy is an antiageing strategy. It refers to selective killing of senescent cells by senolytic agents, strengthening the activity of immune cells that eliminate senescent cells or alleviating the secretory phenotype (SASP) of senescent cells. As senescent cells accumulate with age and are considered to be at the root of age-related disorders, senotherapy seems to be very promising in improving healthspan. Genetic approaches, which allowed to selectively induce death of senescent cells in transgenic mice, provided proof-of-concept evidence that elimination of senescent cells can be a therapeutic approach for treating many age-related diseases. Translating these results into humans is based on searching for synthetic and natural compounds, which are able to exert such beneficial effects. The major challenge in the field is to show efficacy, safety and tolerability of senotherapy in humans. The question is how these therapeutics can influence senescence of non-dividing post-mitotic cells. Another issue concerns senescence of cancer cells induced during therapy as there is a risk of resumption of senescent cell division that could terminate in cancer renewal. Thus, development of an effective senotherapeutic strategy is also an urgent issue in cancer treatment. Different aspects, both beneficial and potentially detrimental, will be discussed in this review.

Keywords: Autophagy; Cancer; Cell senescence; Post-mitotic cells; Senolytics.