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

ABSTRACT

Introduction: 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.

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

Expert opinion: 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.

KEYWORDS:

• aging
• chronic obstructive pulmonary disease
• idiopathic pulmonary fibrosis
• senescent cells
• senolytic drugs

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

This paper was not funded.