Senotherapy for lung diseases

Abstract

Increasing evidence suggests that there is acceleration of lung ageing in chronic lung diseases, such as chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), with the accumulation of senescent cells in the lung. Senescent cells fail to repair tissue damage and release an array of inflammatory proteins, known as the senescence-associated secretory phenotype, which drive further senescence and disease progression. This suggests that targeting cellular senescence with senotherapies may treat the underlying disease process in COPD and IPF and thus reduce disease progression and mortality. Several existing or future drugs may inhibit the development of cellular senescence which is driven by chronic oxidative stress (senostatics), including inhibitors of PI3K-mTOR signalling pathways, antagomirs of critical microRNAs and novel antioxidants. Other drugs (senolytics) selectively remove senescent cells by promoting apoptosis. Clinical studies with senotherapies are already underway in chronic lung diseases.

Keywords: Chronic obstructive pulmonary disease; Idiopathic pulmonary fibrosis; MicroRNA; Senescence-associated secretory phenotype; Senolytic; Senostatic; Sirtuin.