The aging lung: Physiology, disease, and immunity

Cell. 2021 Mar 26;S0092-8674(21)00290-7. doi: 10.1016/j.cell.2021.03.005. Online ahead of print.


The population is aging at a rate never seen before in human history. As the number of elderly adults grows, it is imperative we expand our understanding of the underpinnings of aging biology. Human lungs are composed of a unique panoply of cell types that face ongoing chemical, mechanical, biological, immunological, and xenobiotic stress over a lifetime. Yet, we do not fully appreciate the mechanistic drivers of lung aging and why age increases the risk of parenchymal lung disease, fatal respiratory infection, and primary lung cancer. Here, we review the molecular and cellular aspects of lung aging, local stress response pathways, and how the aging process predisposes to the pathogenesis of pulmonary disease. We place these insights into context of the COVID-19 pandemic and discuss how innate and adaptive immunity within the lung is altered with age.

Keywords: COPD; COVID-19; aging; healthspan; immunity; inflammaging; lung; lung cancer; metabolism; oxidative stress; proteostasis; pulmonary fibrosis; senescence; stress response.

Publication types

  • Review