The Impacts of Cellular Senescence in Elderly Pneumonia and in Age-Related Lung Diseases That Increase the Risk of Respiratory Infections

Abstract

Pneumonia generates considerable negative impacts on the elderly. Despite the widespread uses of vaccines and appropriate antibiotics, the morbidity and mortality of elderly pneumonia are significantly higher compared to the counterparts of young populations. The definitive mechanisms of high vulnerability in the elderly against pathogen threats are unclear. Age-associated, chronic low-grade inflammation augments the susceptibility and severity of pneumonia in the elderly. Cellular senescence, one of the hallmarks of aging, has its own characteristics, cell growth arrest and senescence-associated secretory phenotype (SASP). These properties are beneficial if the sequence of senescence–clearance–regeneration is transient in manner. However, persisting senescent cell accumulation and excessive SASP might induce sustained low-grade inflammation and disruption of normal tissue microenvironments in aged tissue. Emerging evidence indicates that cellular senescence is a key component in the pathogenesis of chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF), which are known to be age-related and increase the risk of pneumonia. In addition to their structural collapses, COPD and IPF might increase the vulnerability to pathogen insults through SASP. Here, we discuss the current advances in understanding of the impacts of cellular senescence in elderly pneumonia and in these chronic lung disorders that heighten the risk of respiratory infections.

Cellular Senescence as a Mechanism and Target in Chronic Lung Diseases

“…There may be increased susceptibility to lung infections as a result of impaired mucociliary clearance and reduced innate and adaptive immunity associated with aging (6).…”

Community-acquired bacterial pneumonia in adult HIV-infected patients

“…Immunosenescence refers to age-related immunological changes that reduce the efficiency of the adaptive and innate immune system, and it is responsible for deterioration in the response to infection and an increase in pathological disorders in the elderly population (28).…”

“…We recommend that such patients do not need treatment, admission, or care sites that differs from that of the general population. 13,14,15,17,18,19,20,22,23,24,25,27,28,29,30,62,63,66,67,68,70,71 A c c e p t e d M a n u s c r i p t…”

Potential Role of Cellular Senescence in Asthma

“…Persistent accumulation of senescent cells during aging induces low-grade inflammation through SASP (Acosta et al, 2013), impairs the immune system (Savale et al, 2009;Albrecht et al, 2014), and increases the vulnerability and susceptibility of organs to various pathological challenges (López-Otín et al, 2013). In respiratory system, cellular senescence has established role in the pathogenesis of aging-related diseases like chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF) (Tsuji et al, 2006;Diaz de Leon et al, 2010;Kuwano et al, 2016;Álvarez et al, 2017;Yanagi et al, 2017;Rashid et al, 2018;Schuliga et al, 2018;Vij et al, 2018;Araya et al, 2019;Fang et al, 2019;Parikh et al, 2019b). However, little is known about the place of cellular senescence in the development of asthma.…”