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
Author Information
Marissa J Schafer: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Thomas A White: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Koji Iijima: Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Andrew J Haak: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Giovanni Ligresti: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Elizabeth J Atkinson: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Ann L Oberg: Division of Biomedical Statistics and Informatics, Department of Health Sciences Research, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Jodie Birch: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing Newcastle upon Tyne NE4 5PL, UK.
Hanna Salmonowicz: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing Newcastle upon Tyne NE4 5PL, UK.
Yi Zhu: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Daniel L Mazula: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Robert W Brooks: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida 33458, USA.
Heike Fuhrmann-Stroissnigg: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida 33458, USA.
Tamar Pirtskhalava: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Y S Prakash: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Tamara Tchkonia: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Paul D Robbins: Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, Florida 33458, USA.
Marie Christine Aubry: Department of Laboratory Medicine and Pathology, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
João F Passos: Institute for Cell and Molecular Biosciences, Newcastle University Institute for Ageing Newcastle upon Tyne NE4 5PL, UK.
James L Kirkland: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
Daniel J Tschumperlin: Department of Physiology and Biomedical Engineering, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Hirohito Kita: Division of Allergic Diseases, Department of Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota 55905, USA.
Nathan K LeBrasseur: Robert and Arlene Kogod Center on Aging, Mayo Clinic College of Medicine, Mayo Clinic 200 First Street Southwest, Rochester, Minnesota 55905, USA.
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.
References
Nature. 2016 Feb 11;530(7589):184-9
[PMID: 26840489]
