Title |
Cellular senescence mediates fibrotic pulmonary disease
|
---|---|
Published in |
Nature Communications, February 2017
|
DOI | 10.1038/ncomms14532 |
Pubmed ID | |
Authors |
Marissa J. Schafer, Thomas A. White, Koji Iijima, Andrew J. Haak, Giovanni Ligresti, Elizabeth J. Atkinson, Ann L. Oberg, Jodie Birch, Hanna Salmonowicz, Yi Zhu, Daniel L. Mazula, Robert W. Brooks, Heike Fuhrmann-Stroissnigg, Tamar Pirtskhalava, Y. S. Prakash, Tamara Tchkonia, Paul D. Robbins, Marie Christine Aubry, João F. Passos, James L. Kirkland, Daniel J. Tschumperlin, Hirohito Kita, Nathan K. LeBrasseur |
Abstract |
Idiopathic pulmonary fibrosis (IPF) is a fatal disease characterized by interstitial remodelling, leading to compromised lung function. Cellular senescence markers are detectable within IPF lung tissue and senescent cell deletion rejuvenates pulmonary health in aged mice. Whether and how senescent cells regulate IPF or if their removal may be an efficacious intervention strategy is unknown. Here we demonstrate elevated abundance of senescence biomarkers in IPF lung, with p16 expression increasing with disease severity. We show that the secretome of senescent fibroblasts, which are selectively killed by a senolytic cocktail, dasatinib plus quercetin (DQ), is fibrogenic. Leveraging the bleomycin-injury IPF model, we demonstrate that early-intervention suicide-gene-mediated senescent cell ablation improves pulmonary function and physical health, although lung fibrosis is visibly unaltered. DQ treatment replicates benefits of transgenic clearance. Thus, our findings establish that fibrotic lung disease is mediated, in part, by senescent cells, which can be targeted to improve health and function. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 23 | 24% |
United Kingdom | 6 | 6% |
Canada | 5 | 5% |
Spain | 3 | 3% |
Germany | 2 | 2% |
India | 2 | 2% |
Korea, Republic of | 1 | 1% |
Mexico | 1 | 1% |
Russia | 1 | 1% |
Other | 6 | 6% |
Unknown | 45 | 47% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Members of the public | 67 | 71% |
Practitioners (doctors, other healthcare professionals) | 13 | 14% |
Scientists | 12 | 13% |
Science communicators (journalists, bloggers, editors) | 3 | 3% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
United Kingdom | 1 | <1% |
Unknown | 809 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 142 | 18% |
Researcher | 131 | 16% |
Student > Bachelor | 77 | 10% |
Student > Master | 69 | 9% |
Student > Doctoral Student | 41 | 5% |
Other | 108 | 13% |
Unknown | 242 | 30% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 216 | 27% |
Medicine and Dentistry | 86 | 11% |
Agricultural and Biological Sciences | 85 | 10% |
Immunology and Microbiology | 34 | 4% |
Pharmacology, Toxicology and Pharmaceutical Science | 27 | 3% |
Other | 100 | 12% |
Unknown | 262 | 32% |