title: Collagen and tissue turnover as a function of age: Implications for fibrosis.
abstract: OBJECTIVE
  The extracellular matrix (ECM) is the backbone of all tissues. It is a complex grid consisting of multiple structural proteins which each play a vital role for the function and maintenance of normal tissue function. In development and growth, tissue is being formed and elaborated (tissue modeling), while in adult life, tissues are being maintained and remodeled. These processes involve likely different mechanisms. During tissue modeling and remodeling, small fragments of proteins are released into the circulation, where they may be used as biomarkers for tissue turnover. The aim of the study was to investigate ECM turnover in rodents as a function of age.
  
  
  METHODS
  Serum of rats of 1, 2, 3, 4, 5, 6, 10 and 12months of age was profiled for 15 markers of ECM turnover, including: fragments of type I, II, III, IV, V and VI collagen formation (P1NP, P4NP-7S, Pro-C5, Pro-C6) and degradation (C1M, C2M, C2M-beta, C3M, C4M, C5M, C6M); biglycan (BGM) and elastin (ELM7) degradation; and the type I and II collagen telopeptides CTX-I and CTX-II.
  
  
  RESULTS
  Type I and II collagen turnover was up to 93% and 97% downregulated in old (one year) compared to young (one month) old animals (p<0.0001), while type IV and V collagen and biglycan turnover was upregulated 2.5-, 2- and 2-fold, respectively (p<0.0001). Type III and VI collagen and elastin turnover was not influenced significantly by age.
  
  
  CONCLUSIONS
  ECM turnover rates were consistently different in young vs. old animals, up to 30 fold. This appears to be due to body growth, a different ECM composition and a higher regenerative capability of connective tissues in young vs. old animals. These changes have to be accounted for in translational science. Both in measuring serum levels of ECM biomarkers and in the development of therapies to speed up wound healing or inhibit fibrogenesis.
authors: Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark. Electronic address: mk@nordicbioscience.com.
authors: Morten A
authors: MA
authors: Karsdal
authors: Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark.
authors: Federica
authors: F
authors: Genovese
authors: Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark.
authors: Emilie A
authors: EA
authors: Madsen
authors: Nordic Bioscience A/S, Herlev Hovedgade, Herlev, Denmark.
authors: Tina
authors: T
authors: Manon-Jensen
authors: Institute of Translational Immunology and Research Center for Immunotherapy, University Medical Center, Mainz, Germany; Division of Gastroenterology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, United States.
authors: Detlef
authors: D
authors: Schuppan
mesh_terms: D000367:Age Factors; D000818:Animals; D015415:Biomarkers / Q000097:blood; D003094:Collagen / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D008106:Liver Cirrhosis, Experimental / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D015415:Biomarkers; D003094:Collagen
keywords: Age; Animal; Biomarkers; Collagen; Elastin; Fibrogenesis; Fibrosis; Liver; MMP; Tissue; Turnover; ccl4