The recent manuscript by Childs et al. in Nature Reviews Drug Discovery 1 thoroughly reviewed the important role senescent cells play in driving ageing and age-related diseases. The review also highlighted the clinical importance of developing senotherapeutic approaches to selectively kill senescent cells (senolytics) or to suppress the senescence-associated secretory phenotype (SASP) that drives sterile inflammation associated with ageing (senomorphics), in order to extend healthspan and potentially lifespan. Clearly, senotherapeutic approaches can revolutionize how age-related diseases and ultimately how ageing itself can be treated. Given how quickly the field of senotherapeutics is moving towards clinical trials, we would like to expand upon several important issues regarding the current and future development of senotherapeutics. This is particularly important since the nascent field of senotherapeutics is faced with the challenge of establishing important standards and criteria for documenting a compound's or a combination of compounds' function as advertised, that is, as senotherapeutics.

It is established that senescent cells play a causative role in ageing and age-related disease. Therefore, the development of drugs that specifically kill senescent cells is envisioned to have significant therapeutic effects on slowing ageing phenotypes, treating age-related comorbidities and improving resiliency. However, not all senescent cells are the same, expressing different senescence markers, secreting different SASP factors and, more importantly, using different senescent cell anti-apoptotic pathways (SCAPs) to resist apoptosis. The elimination of senescent cells from multiple tissues or even a single tissue will probably require the combination of multiple senotherapeutic drugs 2.