Recent Advances in Molecular Basis of Lung Aging and Its Associated Diseases

Abstract

Aging is often viewed as a progressive decline in fitness due to cumulative deleterious alterations of biological functions in the living system. Recently, our understanding of the molecular mechanisms underlying aging biology has significantly advanced. Interestingly, many of the pivotal molecular features of aging biology are also found to contribute to the pathogenesis of chronic lung disorders such as chronic obstructive pulmonary disease and idiopathic pulmonary fibrosis, for which advanced age is the most crucial risk factor. Thus, an enhanced understanding of how molecular features of aging biology are intertwined with the pathobiology of these aging-related lung disorders has paramount significance and may provide an opportunity for the development of novel therapeutics for these major unmet medical needs. To serve the purpose of integrating molecular understanding of aging biology with pulmonary medicine, in this review, recent findings obtained from the studies of aging-associated lung disorders are summarized and interpreted through the perspective of molecular biology of aging.

Nucleotide‐binding domain and leucine‐rich‐repeat‐containing protein X1 deficiency induces nicotinamide adenine dinucleotide decline, mechanistic target of rapamycin activation, and cellular senescence and accelerates aging lung‐like changes

“…It is a major challenge to elucidate how scientific advances in molecular insights of aging biology can be integrated into a conceptual framework that will illuminate the mechanistic understanding of lung aging and its related disorders (Budinger et al, 2017). Besides, the body of scientific knowledge related to lung aging and its contribution to the pathobiology of chronic lung diseases is lagging far behind other recent advances in aging biology (Kang, 2020). Regarding this, we previously reported that, from three independent human COPD cohorts, the expression of NLRX1 was suppressed in the lungs from patients with COPD and this suppression showed a strong correlation with the degree of airflow limitation, a hallmark of COPD (Kang et al, 2015).…”

“…Our previous study reported the pathogenic role of NLRX1, which may contribute to the development of chronic obstructive pulmonary disease (COPD) (Kang et al, 2015). Additionally, there is growing evidence that aging hallmarks are noticeable features of COPD (Easter et al, 2020;Kang, 2020). Indeed, when we assessed the level of NLRX1 expression with normative aging in murine lungs, both mRNA and protein expression levels of NLRX1 were significantly reduced in 12-and 24-month-old (mo) mice compared with those of young (3-months) mice (Figure 5a-c and Figure S1a,b).…”

Specific epigenetic regulators serve as potential therapeutic targets in idiopathic pulmonary fibrosis

“…Calorie restriction (CR) diets have proven to be beneficial in combating disorders such as pulmonary fibrosis, which is linked to oxidative stress and old age [ 191 , 192 ]. In order to elucidate the effects of the CR diet on oxidative stress, Qui et al.…”

“…Increased TGF-β signalling decreases SIRT3 levels, resulting in increased levels of acetylated SOD2 followed by a rise in oxidative stress that is favourable for FMD [179,189]. Calorie restriction (CR) diets have proven to be beneficial in combating disorders such as pulmonary fibrosis, which is linked to oxidative stress and old age [191,192]. In order to elucidate the effects of the CR diet on oxidative stress, Qui et al fed CR diet to Sirt3 knockout mice and also to their wild-type counterparts.…”

Mitochondrial antiviral signaling protein is crucial for the development of pulmonary fibrosis

“…By demonstrating that bleomycin injury-induced cellular senescence is significantly attenuated in a MAVS-dependent manner, our study may provide additional mechanistic insight of how MAVS contributes to the development of pulmonary fibrosis. The significance of these novel observations should be explored in future studies, considering that cellular senescence has emerged as a crucial driving force of IPF pathogenesis [25,26,38].…”