Causes of Pulmonary Fibrosis in the Elderly

Abstract

Idiopathic pulmonary fibrosis (IPF) is the most common and most lethal type of idiopathic interstitial pneumonia. It is a chronic, aging-associated lung disease characterized by fibrotic foci and inflammatory infiltrates, with no cure and very limited therapeutic options. Although its etiology is unknown, several pathogenic pathways have been described that could explain this process, involving aging, environmental factors, genomic instability, loss of proteostasis, telomere attrition, epigenetic changes, mitochondrial dysfunction, cell senescence, and altered intercellular communication. One of the main prognostic factors for the development of IPF in broad epidemiological studies is age. The incidence increases with age, making this a disease that predominantly affects the elderly population, being exceptional under 45 years of age. However, the degree to which each of these mechanisms is involved in the etiology of the uncontrolled fibrogenesis that defines IPF is still unknown. Clarifying these questions is crucial to the development of points of intervention in the pathogenesis of the disease. This review briefly summarizes what is known about each possible etiological factor, and the questions that most urgently need to be addressed.

Emerging cellular and molecular determinants of idiopathic pulmonary fibrosis

“…The impaired tissue homeostasis favors the release of intermediates, such as pro-inflammatory cytokines and metalloproteinases, collectively referred to as the 'secretory phenotype related to aging' (SPRA). Factors which further affect premature aging include telomere deficiency, mitochondrial dysfunction, oxidative stress, DNA damage, and altered protein function; most of these factors have been reported to play pivotal roles in the pathophysiology of IPF [72][73][74][75].…”

The Role of Occupational and Environmental Exposures in the Pathogenesis of Idiopathic Pulmonary Fibrosis: A Narrative Literature Review

“…The pathogenesis of IPF is incompletely understood. However, accumulating evidence, obtained over the past three decades, suggests that several risk factors are associated with the development of IPF, including advanced age, male gender, genetic factors, smoking and other environmental exposures [23,24,25,26]. A great deal of attention has been directed towards elucidating the role of genetic factors in the pathogenesis of IPF.…”

Identification and Validation of Aging-Related Genes in Idiopathic Pulmonary Fibrosis

“…Some of the risk factors related to the incidence of IPF include smoking and old age ( Hill et al, 2019 ; Rahaghi et al, 2020 ), and more men are affected by IPF than women. The occurrence rate of IPF and its related mortality rate increase substantially with age ( Ebner et al, 2020 ; Phan et al, 2021 ); two-thirds of patients with IPF are aged 60 years or more at the onset of the disease and the average age at the time of diagnosis is 66 years; the estimated prevalence of IPF among individuals over 65 years of age may be as high as 94 per 100,000 people ( Hecker et al, 2014 ; Ryerson et al, 2016 ; López-Ramírez et al, 2018 ; Kishaba, 2019 ; Lee et al, 2020 ). At present, the key treatment approaches for IPF are based mainly on the symptoms and have low therapeutic effects; the 5 year survival rate after diagnosis is less than 50%, and the median survival time is only 2–3 years ( Kistler et al, 2014 ; Yoshihara et al, 2020 ).…”