Ageing mechanisms that contribute to tissue remodeling in lung disease

Abstract

Age is a major risk factor for chronic respiratory diseases such as idiopathic pulmonary fibrosis (IPF), chronic obstructive pulmonary disease (COPD) and certain phenotypes of asthma. The recent COVID-19 pandemic also highlights the increased susceptibility of the elderly to acute respiratory distress syndrome (ARDS), a diffuse inflammatory lung injury with often long-term effects (ie parenchymal fibrosis). Collectively, these lung conditions are characterized by a pathogenic reparative process that, rather than restoring organ function, contributes to structural and functional tissue decline. In the ageing lung, the homeostatic control of wound healing following challenge or injury has an increased likelihood of being perturbed, increasing susceptibility to disease. This loss of fidelity is a consequence of a diverse range of underlying ageing mechanisms including senescence, mitochondrial dysfunction, proteostatic stress and diminished autophagy that occur within the lung, as well as in other tissues, organs and systems of the body. These ageing pathways are highly interconnected, involving localized and systemic increases in inflammatory mediators and damage associated molecular patterns (DAMPs); along with corresponding changes in immune cell function, metabolism and composition of the pulmonary and gut microbiomes. Here we comprehensively review the roles of ageing mechanisms in the tissue remodeling of lung disease.

Keywords: Acute respiratory distress syndrome (ARDS); Chronic obstructive pulmonary disease (COPD); Damage associated molecular pattern (DAMP); Idiopathic pulmonary fibrosis (IPF); Immunosenescence; Mitochondrial dysfunction.