Senolytic drugs in respiratory medicine: is it an appropriate therapeutic approach?

Aging is the major risk factor for most of the chronic diseases. Cellular senescence is one of the main hallmarks of aging. A growing body of evidence implicates accelerated mechanisms of aging, including cellular senescence, in idiopathic pulmonary fibrosis (IPF) and chronic obstructive pulmonary disease (COPD) pathogenesis. Senolytics are pharmaceutical agents that eliminate senescent cells, thus blocking tissue degeneration and late life complications and allowing tissue regeneration.

The potential use of senolytic drugs in respiratory medicine is examined and discussed.

The promising signal generated by preclinical studies supports proof-of-principle clinical studies with senolytic agents in the treatment of IPF, but this signal is not very strong, and furthermore, senolytic drugs could be detrimental in IPF patients. On the other hand, the preclinical evidence that these agents are able to influence the natural history of COPD is still lacking. COPD is a very heterogeneous lung disease presenting different (mixed) phenotypes. Given the difference in underlying pathology of these phenotypes, it can be envisaged that lung aging is more or differently involved in some of these phenotypes than others. Consequently, it will be difficult to determine which COPD patient will benefit from a treatment with senolytics.