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Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs.

作者信息

Calhoun Cheresa, Shivshankar Pooja, Saker Mirna, Sloane Lauren B, Livi Carolina B, Sharp Zelton D, Orihuela Carlos J, Adnot Serge, White Eric S, Richardson Arlan, Le Saux Claude Jourdan

机构信息

Division of Cardiology, Department of Medicine, University of Texas Health Science Center at San Antonio.

Team 8, INSERM U955-Biomedical Research of Mondor Institute, University of Paris East, Créteil, France.

出版信息

J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):153-60. doi: 10.1093/gerona/glu241. Epub 2015 Jan 7.

Abstract

Age-associated decline in organ function governs life span. We determined the effect of aging on lung function and cellular/molecular changes of 8- to 32-month old mice. Proteomic analysis of lung matrix indicated significant compositional changes with advanced age consistent with a profibrotic environment that leads to a significant increase in dynamic compliance and airway resistance. The excess of matrix proteins deposition was associated modestly with the activation of myofibroblasts and transforming growth factor-beta signaling pathway. More importantly, detection of senescent cells in the lungs increased with age and these cells contributed toward the excess extracellular matrix deposition observed in our aged mouse model and in elderly human samples. Mechanistic target of rapamycin (mTOR)/AKT activity was enhanced in aged mouse lungs compared with those from younger mice associated with the increased expression of the histone variant protein, MH2A, a marker for aging and potentially for senescence. Introduction in the mouse diet of rapamycin, significantly blocked the mTOR activity and limited the activation of myofibroblasts but did not result in a reduction in lung collagen deposition unless it was associated with prevention of cellular senescence. Together these data indicate that cellular senescence significantly contributes to the extracellular matrix changes associated with aging in a mTOR 1-dependent mechanism.

摘要

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