“…Currently, first world countries are experiencing an increase in populations over the age of 60 as never seen before Approximately 16% of the US population is over the age of 65 [42], while 22% is over the age of 60 in the United Kingdom [43]; 24% of German citizens are age 60 or older [44] Notably, Germany experienced their largest number of centenarians in 2020 at over 20 000 individuals [44], emphasizing the growing importance of understanding the biological complexities of ageing Additionally, respiratory diseases are a leading cause of death worldwide whether chronic such as chronic obstructive pulmonary disorder (COPD) or acute such as a lower respiratory infection [45,46] Age-related changes of the lung encompass reduction in thoracic cavity size and respiratory force [47] as well as changes which disrupt cellular and molecular homeostasis [48], culminating in an increased risk of respiratory failure for individuals over the age of 60 [49] As we age, there is an exponential atrophy of skeletal muscle function surrounding the thoracic cavity [50,51] reducing its total volume capacity and reducing inspiratory and expiratory strength [52] The strength of the thoracic diaphragm, the dominant muscle involved in respiration, is significantly reduced in adults 67 and over [53] Pathogen clearance and response is significantly reduced as we age The first line of defense within the upper and lower airways is mucociliary clearance which also becomes impaired with age [54,55] This is particularly impactful when considering that expiratory strength is required for adequate clearance of particulates that cannot be cleared through mucociliary action [56,57] These structural changes demonstrate a reduced ability for elderly individuals to meet respiratory needs should pulmonary stress occur (Fig. 1) In normal ageinglungs, transcriptomic studies have revealed permanent re-modeling of the extracellular matrix Parenchymal tissue composition in mice 24 months old (aged), as opposed to 8 week-old mice (young), exhibit increased expression of the pro-fibrotic cytokines IL-1b, IL-6, and TNF-a [58 ] It is well established that lung fibrosis can impair normal lung function [59], and ageing promotes lung fibrosis Patients with sarcoidosis experience an upregulation in these same pro-fibrotic cytokines [60].…”