Regeneration of the Aging Lung: A Mini-Review.
Natural lung aging is marked by molecular changes that occur during development, maturation, and late-life decline. At the cellular and whole organ level, degenerative changes that are a hallmark of natural aging (shorter telomeres, increased expression of cellular senescence markers, increased DNA damage, oxidative stress, and apoptosis, accompanied by diminished elasticity) reach pathological levels in aging humans in the form of chronic respiratory disease. Aging strongly correlates with the development and incidence of chronic respiratory diseases, including cancer and idiopathic pulmonary fibrosis, but is most strongly linked with development of chronic obstructive pulmonary disease. Lung failure due to aging can be traced to loss of lung stem cell regenerative capacity within the distinctive stem cell niches found within each compartment of the lung. Current knowledge about the identity and function of these stem cell compartments has been largely drawn from a variety of transgenic and spontaneously mutated mouse models that are characterized by rapid rates of aging or have been used to examine regeneration from injury in the context of natural or accelerated aging. While much work has focused on the failure of epithelial cell populations as a key component of the aging process, additional studies have shown that aging, as a global phenomenon in the lung, also impacts resident endothelial, mesenchymal, and immune cell populations. In this review, we examine aging as a process dependent on specific changes in molecular pathways within multiple lung cell populations.
Developmental Biology and Regenerative Medicine, Saban Research Institute, Children's Hospital Los Angeles, Los Angeles, Calif., USA.
Sonia
S
Navarro
Barbara
B
Driscoll
D000375:Aging / Q000473:pathology / Q000502:physiology*; D000818:Animals; D016922:Cellular Senescence / Q000502:physiology; D006801:Humans; D008168:Lung / Q000473:pathology / Q000502:physiology*; D008171:Lung Diseases / Q000209:etiology / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D023421:Models, Animal; D012038:Regeneration / Q000502:physiology*; D055153:Stem Cell Niche / Q000502:physiology