PMID- 25568097
OWN - NLM
STAT- MEDLINE
DCOM- 20160509
LR  - 20211203
IS  - 1758-535X (Electronic)
IS  - 1079-5006 (Print)
IS  - 1079-5006 (Linking)
VI  - 71
IP  - 2
DP  - 2016 Feb
TI  - Senescent Cells Contribute to the Physiological Remodeling of Aged Lungs.
PG  - 153-60
LID - 10.1093/gerona/glu241 [doi]
AB  - 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.
CI  - (c) The Author 2015. Published by Oxford University Press on behalf of The 
      Gerontological Society of America. All rights reserved. For permissions, please 
      e-mail: journals.permissions@oup.com.
FAU - Calhoun, Cheresa
AU  - Calhoun C
AD  - Division of Cardiology, Department of Medicine, University of Texas Health 
      Science Center at San Antonio.
FAU - Shivshankar, Pooja
AU  - Shivshankar P
AD  - Division of Cardiology, Department of Medicine, University of Texas Health 
      Science Center at San Antonio.
FAU - Saker, Mirna
AU  - Saker M
AD  - Team 8, INSERM U955-Biomedical Research of Mondor Institute, University of Paris 
      East, Creteil, France.
FAU - Sloane, Lauren B
AU  - Sloane LB
AD  - Sam and Ann Barshop Institute of Aging and Longevity Studies.
FAU - Livi, Carolina B
AU  - Livi CB
AD  - Sam and Ann Barshop Institute of Aging and Longevity Studies, Department of 
      Molecular Medicine.
FAU - Sharp, Zelton D
AU  - Sharp ZD
FAU - Orihuela, Carlos J
AU  - Orihuela CJ
AD  - Department of Microbiology and Immunology, University of Texas Health Science 
      Center at San Antonio.
FAU - Adnot, Serge
AU  - Adnot S
AD  - Team 8, INSERM U955-Biomedical Research of Mondor Institute, University of Paris 
      East, Creteil, France.
FAU - White, Eric S
AU  - White ES
AD  - Department of Pulmonary and Critical Care Medicine, University of Michigan 
      Medical School, Ann Arbor.
FAU - Richardson, Arlan
AU  - Richardson A
AD  - Sam and Ann Barshop Institute of Aging and Longevity Studies.
FAU - Le Saux, Claude Jourdan
AU  - Le Saux CJ
AD  - Division of Cardiology, Department of Medicine, University of Texas Health 
      Science Center at San Antonio. lesaux@uthscsa.edu.
LA  - eng
GR  - AG036613/AG/NIA NIH HHS/United States
GR  - RC2AG036613/AG/NIA NIH HHS/United States
GR  - R01 AI114800/AI/NIAID NIH HHS/United States
GR  - U01 HL111016/HL/NHLBI NIH HHS/United States
GR  - R01 CA193835/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20150107
PL  - United States
TA  - J Gerontol A Biol Sci Med Sci
JT  - The journals of gerontology. Series A, Biological sciences and medical sciences
JID - 9502837
RN  - 0 (Actins)
RN  - 0 (Biomarkers)
RN  - 0 (Tenascin)
RN  - 0 (Transforming Growth Factor beta)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.1.1 (mTOR protein, mouse)
RN  - EC 2.7.11.1 (TOR Serine-Threonine Kinases)
SB  - IM
MH  - Actins/metabolism
MH  - Adult
MH  - Aged
MH  - Aging/physiology
MH  - Airway Remodeling/*physiology
MH  - Animals
MH  - Biomarkers/metabolism
MH  - Cellular Senescence/*physiology
MH  - Collagen/metabolism
MH  - Extracellular Matrix/metabolism
MH  - Fibroblasts/metabolism
MH  - Humans
MH  - Lung/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Middle Aged
MH  - Proteomics
MH  - Signal Transduction/physiology
MH  - TOR Serine-Threonine Kinases/metabolism
MH  - Tenascin/metabolism
MH  - Transforming Growth Factor beta/metabolism
PMC - PMC4861645
OTO - NOTNLM
OT  - Aging
OT  - Rapamycin
OT  - Remodeling
OT  - Senescence
OT  - mTOR pathway
EDAT- 2015/01/09 06:00
MHDA- 2016/05/10 06:00
PMCR- 2017/02/01
CRDT- 2015/01/09 06:00
PHST- 2014/09/15 00:00 [received]
PHST- 2014/11/25 00:00 [accepted]
PHST- 2015/01/09 06:00 [entrez]
PHST- 2015/01/09 06:00 [pubmed]
PHST- 2016/05/10 06:00 [medline]
PHST- 2017/02/01 00:00 [pmc-release]
AID - glu241 [pii]
AID - 10.1093/gerona/glu241 [doi]
PST - ppublish
SO  - J Gerontol A Biol Sci Med Sci. 2016 Feb;71(2):153-60. doi: 10.1093/gerona/glu241. 
      Epub 2015 Jan 7.