Mechanisms and consequences of oxidative stress in lung disease: therapeutic implications for an aging populace

Abstract

The rapid expansion of the elderly population has led to the recent epidemic of age-related diseases, including increased incidence and mortality of chronic and acute lung diseases. Numerous studies have implicated aging and oxidative stress in the pathogenesis of various pulmonary diseases; however, despite recent advances in these fields, the specific contributions of aging and oxidative stress remain elusive. This review will discuss the consequences of aging on lung morphology and physiology, and how redox imbalance with aging contributes to lung disease susceptibility. Here, we focus on three lung diseases for which aging is a significant risk factor: acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), and idiopathic pulmonary fibrosis (IPF). Preclinical and clinical development for redox- and senescence-altering therapeutic strategies are discussed, as well as scientific advancements that may direct current and future therapeutic development. A deeper understanding of how aging impacts normal lung function, redox balance, and injury-repair processes will inspire the development of new therapies to prevent and/or reverse age-associated pulmonary diseases, and ultimately increase health span and longevity. This review is intended to encourage basic, clinical, and translational research that will bridge knowledge gaps at the intersection of aging, oxidative stress, and lung disease to fuel the development of more effective therapeutic strategies for lung diseases that disproportionately afflict the elderly.

Elevated truncated oxidized phospholipids as a factor exacerbating ALI in the aging lungs

“…Impaired antioxidant defense (deregulated redox balance control) is a well-recognized factor associated with aging, which significantly impacts both physiologic and pathologic processes (4,24). Aging populations suffer from more severe lung injury caused by bacterial pathogens, delayed recovery, and increased mortality (12,31). Although the impact of redox disbalance in more severe inflammatory response observed in aging population is evident, specific mediators generated as result of activated oxidation and contributing to more severe lung injury, inflammation and barrier dysfunction have not been precisely characterized.…”

“…Weakening of the antioxidant defense and activation of redox-dependent pathologic processes in aging populations is well recognized (12,23,24). We next evaluated Tr-OxPL profiles in the lungs of control and LPSstimulated young and aging mice.…”

“…Under these conditions, lung vascular barrier function is largely compromised and truncated oxidized phospholipid products (Tr-OxPLs) such as 1-palmitoyl-2-(5-oxovaleroyl)-sn-glycero-phosphocholine (POVPC), 1-palmitoyl-2-glutaroyl-sn-glycero-phosphocholine (PGPC), and lysophosphocholine (lyso-PC) increase permeability in EC monolayer cultures (9,10), thus potentially contributing to endothelial barrier disruption and lung injury in vivo. Given the reduction of antioxidant capacity associated with aging and reflected by decreased expression and activation of antioxidant enzymes, reduced glutathione buffering capacity, and other alterations (11,12), the production of Tr-OxPLs may have an increased role in more severe ALIs observed in an aging population, and this question warrants further investigation.…”

Intravenous vitamin C for reduction of cytokines storm in acute respiratory distress syndrome

“…The severe increased oxidative stress causes pulmonary injuries: lung injury (ALI) and ARDS. ALI and ARDS are key factors responsible for substantially high morbidity and mortality [120,121]. An increase of C-reactive protein (hsCRP), an indicator of inflammation and oxidative stress is seen among Covid19 patients [122].…”

Can early and high intravenous dose of vitamin C prevent and treat coronavirus disease 2019 (COVID-19)?

“…ARDS, characteristic of severe hypoxemia, is usually accompanied by uncontrolled inflammation, oxidative injury and damage to the alveolar-capillary barrier [4]. Increased oxidative stress is a major insult in pulmonary injury including acute lung injury (ALI) and ARDS, two clinical manifestations of acute respiratory failure with substantially high morbidity and mortality [5,6].…”