Does the Existence of Senolytic Compounds Underpin that Anti-Senolytics MayExist? A View on the Heaven and Hell of Cellular Senescence

The discovery of compounds that can selectively target senescent cells (called senolytic compounds) has moved lot of research around this new field of development ofdrugs and nutraceutical compounds. The promises, expectations and innovations in the therapy of age-related pathologies characterized by an increased low grade chronicinflammatory status [which is likely driven in part by the senescence- associated secretoryphenotype (SASP) produced by accumulating senescent cells] are so high that we are tempted to describe this field as a new scientific “Heaven”. However, if this Heaven is real, that might seem to suggest that Hell is also real. In this case the term “Hell” refers not only to the potential side-effects of senolytic compounds and to the pro-senescence effects displayed by other compounds, but also to the possibility that real “anti-senolytics” exist. We cannot exclude that among common drugs (in particular those asso- ciated with chronic side-effects in elderly) or natural bioactive compounds there are molecules able to promote resistance to apoptosis in senescent cells, or able to depress senescence immu- nesurveillance thus promoting accumulation of senescent cells. Comparing differential effects of drugs and bioactive compounds in senescent versusnormal cells could ameliorate the develop- ment of drugs and nutraceuticals tailored to the needs of elderly people.