Age-related alterations in collagen and total protein metabolism determined in cultured rat dermal fibroblasts: age-related trends parallel those observed in rat skin in vivo.
The cultured fibroblast has been extensively used as a model system to study aging. However, few studies have examined the veracity of observations obtained in cultured fibroblasts aged in vitro to those made in animal tissues in vivo. This paper compares age-related alterations in collagen metabolism measured in cultured cells with previously reported results in the aging rat (Mays et al. (1991) Biochem. J. 276, 307-313). Age-related changes in collagen synthesis in rat skin fibroblasts in vitro over 30 population doublings were determined based on the production of hydroxy-[14C]proline. Degradation of newly synthesized collagen was based on the appearance of free hydroxy-[14C]proline in the culture system. Total protein synthesis rates were based on the incorporation of [14C]proline into proteins. In vitro rates of collagen synthesis decreased 5-fold over 30 population doublings (P < 0.05). Degradation of newly synthesized collagen increased from 33.0 +/- 0.8% (n = 4, SEM) to 45.2 +/- 1.1% (n = 4; P < 0.05) over the same period, with a maximum after 25 population doublings of 55.8 +/- 1.1% (n = 4). Total protein synthesis rates decreased by one-half over 30 population doublings (P < 0.05). The results indicated that collagen production decreased as cells aged in vitro and that this was due to both changes in synthesis and degradation. The results demonstrate that age-related alterations in collagen and total protein metabolism of skin fibroblasts in culture were similar to those reported previously for skin in vivo, suggesting that for studies of these processes, fibroblasts in culture provide an appropriate model.
Mays
P K
PK
Centre for Respiratory Research, University College London Medical School, Rayne Institute, U.K.
McAnulty
R J
RJ
Campa
J S
JS
Laurent
G J
GJ
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D003094:Collagen / Q000378:metabolism*; D005347:Fibroblasts / Q000378:metabolism*; D006909:Hydroxyproline / Q000378:metabolism; D011392:Proline / Q000378:metabolism; D051381:Rats; D012867:Skin / Q000166:cytology / Q000378:metabolism*
D003094:Collagen; D011392:Proline; D006909:Hydroxyproline