PROTEIN-TURNOVER DURING AGING OF CULTURED HUMAN FIBROBLASTS

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. © 1990, Canadian Association on Gerontology. All rights reserved.