A Close Link Between Cellular Senescence and Idiopathic Pulmonary Fibrosis
Evidence has accumulated in recent years for the accumulation of senescent cells in aged tissues to be an important driver of fibrosis, particularly the evidence resulting from studies that employed senolytic therapies to selectively destroy sensescent cells and thereby reverse fibrosis. Fibrosis is a malfunction of tissue maintenance, in which cells deposit excessive collagen to form scar-like structures that disrupt organ function. There is comparatively little that can be done to treat patients with fibrotic disease at present, and so there is considerable interest in any new path to therapy. Senescent cells secrete pro-inflammatory, pro-growth factors, and thus they are the prime suspects in many disruptions of normal tissue maintenance processes.
Aging is an inevitable and complex natural phenomenon due to the increase in age. Cellular senescence means a non-proliferative but viable cellular physiological state. It is the basis of aging, and it exists in the body at any time point. Idiopathic pulmonary fibrosis (IPF) is an interstitial fibrous lung disease with unknown etiology, characterized by irreversible destruction of lung structure and function. Aging is one of the most critical risk factors for IPF, and extensive epidemiological data confirms IPF as an aging-related disease.
Senescent fibroblasts in IPF show abnormal activation, telomere shortening, metabolic reprogramming, mitochondrial dysfunction, apoptosis resistance, autophagy deficiency, and senescence-associated secretory phenotypes (SASP). These characteristics of senescent fibroblasts establish a close link between cellular senescence and IPF. The treatment of senescence-related molecules and pathways is continually emerging, and using senolytics eliminating senescent fibroblasts is also actively tried as a new therapy for IPF.