Emphysema is a leading cause of disability and mortality in the United States and worldwide. Aside from cigarette smoke, age is the biggest risk factor for emphysema development. Emphysema has been considered by some as an age-related disease because the alveolar destruction that is its hallmark occurs in the normal aging lung. Telomere dysfunction is one of the best-characterized mechanisms of cellular aging. Our group has recently shown that telomere dysfunction is a determinant of emphysema susceptibility in mice as well as in some human families. This application builds on these findings to probe the mechanisms underlying telomere-mediated emphysema. Our focus is primarily on understanding how epithelial damage and cellular senescence contribute to emphysema, with age and in response to cigarette smoke.
The specific aims build on compelling data showing that telomere dysfunction in epithelial cells limits repair after injury, ad test whether telomere length is a relevant determinant of stem cell function in alveolar progenitor cells. Our proposed studies aim to advance paradigms of emphysema biology in the context of aging mechanisms with the goal of identifying new understanding of disease mechanisms and novel targets for treatment.

Public Health Relevance

Emphysema is a major cause of disability, and it is the third leading cause of death in the United States. There are currently no effective treatments that slow its progressive course. Age is the biggest risk factor for emphysema; and this project aims to define the role of telomeres, a well-established mechanism of cellular aging, in emphysema biology with the goal of defining new paradigms for approaching its treatment.

National Institute of Health (NIH)
National Heart, Lung, and Blood Institute (NHLBI)
Research Project (R01)
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Study Section
Lung Injury, Repair, and Remodeling Study Section (LIRR)
Program Officer
Postow, Lisa
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Johns Hopkins University
Internal Medicine/Medicine
Schools of Medicine
United States
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Cárdenes, Nayra; Álvarez, Diana; Sellarés, Jacobo et al. (2018) Senescence of bone marrow-derived mesenchymal stem cells from patients with idiopathic pulmonary fibrosis. Stem Cell Res Ther 9:257
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