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Protein Turnover During Aging of Cultured Human Fibroblasts

Published online by Cambridge University Press:  29 November 2010

Calvin B. Harley  and
Samuel Goldstein
Calvin B. Harley
Affiliation:
McMaster University
Samuel Goldstein
Affiliation:
University of Arkansas for Medical Sciences and GRECC J.L. McClellan Memorial Veterans Hospital
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Abstract

When cells are allowed to age in vitro, or are taken from aged normal donors or subjects with features of accelerated aging (progeria or Werner syndrome), they may be considered 'old'. Such old cells have reduced growth rates in culture compared to early or mid-passage cells from young normal donors. During exponential growth the rate constants for protein synthesis were not significantly different between young and old cells (0.023±0.002 h1 vs. 0.021±0.002 h1, respectively), yet growth rates (i.e. protein accretion) were only 0.013±0.003 h1 in old cells compared to 0.022±0.002 h1 in young cells. Thus, the reduced rate of protein accumulation during growth of old cells compared to young cells was associated with increased protein degradation (0.01+0.002 h1 vs. 0.001±0.002 h1; P<0.05) rather than reduced rates of protein synthesis. When cells entered quiescence from density dependent inhibition of growth, protein synthetic rates decreased in both young and old cells to comparable levels (0.013±0.002 h1) with the result that rates of growth (0.003±0.0003 h1) and degradation (0.01±0.003h1) were not significantly different between the two groups. Thus, a difference in protein turnover between young and old cells was only seen during exponential growth, where degradation was increased in old cells. The causal relationship between increased protein degradation and decreased growth rates in old cells is not known.

Résumé

Les cellules qui vieillissent in vitro ou bien celles qui sont prélevées de donneurs d'àge avancé ou de sujets manifestant certaines des particularités qui s'apparentent à un vieillissement accéléré (progérie ou le syndrome de Werner), peuvent être qualifiées de 'vieilles'. Celles-ci on des taux de croissance ralentis en milieu de culture si on les compare aux cellules nouvelles ou à mi-passage prélevées de jeunes donneurs normaux. Durant la croissance exponentielle, les taux de constantes pour la synthèse protéique dans les jeunes cellules ne sont pas significativement différents de ceux retrouvés dans les vieilles cellules (0.023 ± 0.002 h1 vs. 0.021 ± 0.002 h1 respectivement) et pourtant les taux de croissance (i.e. accrétion protéique) sont de seulement 0.013±0.003 h1 dans les vieilles cellules comparés à 0.022±0.002 h1 dans les jeunes cellules. Done, le taux ralenti d'accumulation protéique durant la croissance des vieilles cellules comparé aux jeunes cellules est associé à une dégradation protéique accélérée (0.01±0.002h1 vs 0.001 ±0.002 h1; P <0.05) plutôt qu'à des taux ralentis de synthèse protéique. Lorsque les cellules deviennent quiescentes suivant une période d'inhibition de croissance due à la densité, les taux de synthèse protéique diminuent dans les jeunes et les vieilles cellules pour aboutir à des niveaux comparables (0.013±0.002 h1) où les taux de croissance (0.003±0.0003 h1) et de dégradation (0.01±0.003 h1) ne sont significativement pas differents dans les deux groupes. Done, ce n'est qu'en période de croissance exponentielle qu'une différence dans le turn-over protéique entre jeunes et vieilles cellules est observée, alors que la dégradation est accélérée dans les vieilles cellules. La relation causale entre la dégradation protéique accélérée et les taux de croissance ralentis dans les vieilles cellules demeure inconnue.

Keywords

Protein TurnoverFibroblastsCell CultureCellular Senescence.
Type
Articles
Information
Canadian Journal on Aging / La Revue canadienne du vieillissement , Volume 9 , Issue 2 , Summer/Été 1990 , pp. 177 - 187
Copyright
Copyright © Canadian Association on Gerontology 1990

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