The extracellular
matrix (ECM) is the backbone of all tissues. It is a co
mplex grid consisting of
multiple structural proteins which each play a vital role for the function and
maintenance of nor
mal tissue function. In develop
ment and growth, tissue is being for
med and elaborated (tissue
modeling), while in adult life, tissues are being
maintained and re
modeled. These processes involve likely different
mechanis
ms. During tissue
modeling and re
modeling, s
mall frag
ments of proteins are released into the circulation, where they
may be used as bio
markers for tissue turnover. The ai
m 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 12 months 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 (m>pm> <0.0001), while type IV and V collagen and biglycan turnover was upregulated 2.5-, 2- and 2-fold, respectively (m>pm> <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 m>vs.m> 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 m>vs.m> 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.