Revealing the Pathogenic and Aging-related Mechanisms of the Enigmatic Idiopathic Pulmonary Fibrosis. An Integral Model

• DOI: 10.1164/rccm.201312-2221pp
• Publication Date: 2014-03-18T17:06:33Z
• Authors: Moisés Selman; Annie Pardo
• Keywords: 0301 basic medicine; Aging; Evidence-Based Medicine; Incidence; Smoking; Telomere Homeostasis; Genomic Instability; Idiopathic Pulmonary Fibrosis; Epigenesis, Genetic; 3. Good health; Pulmonary Alveoli; Oxidative Stress; Pulmonary Disease, Chronic Obstructive; 03 medical and health sciences; Age Distribution; Risk Factors; Prevalence; Humans; Cellular Senescence

A growing body of evidence indicates that aberrant activation alveolar epithelial cells and fibroblasts in an aging lung plays a critical role the pathogenesis idiopathic pulmonary fibrosis (IPF). However, biopathological processes linking with IPF mechanisms responsible for abnormal have not been elucidated. Many hallmarks (e.g., genomic instability, telomere attrition, epigenetic alterations, mitochondrial dysfunction, cellular senescence) proposed as essential development IPF; however, these disturbances are restricted to also occur other aging-related disorders, primarily chronic obstructive disease (COPD). Therefore, unanswered question is why current/former smoker about 60 years age shorter telomeres, senescence, excessive oxidative stress, dysfunction develops COPD; words, what makes old lungs specifically susceptible develop IPF? In this Perspective, we propose integral model which combination some gene variants and/or expression results loss integrity consequently failure alveoli correctly respond injury face stress associated mechanical stretch. Afterward, distinctive "reprogramming" affects both provokes, among others, recapitulation developmental pathways miscommunication between cell types, resulting exaggerated production accumulation extracellular matrix subsequent destruction architecture.