Altered rates of collagen synthesis in in vitro aged human lung fibroblasts

Absolute rates of protein and collagen synthesis based on prolyl-tRNA as the precursor were determined in two age groups of IMR-90 human lung fibroblasts. Compared with midrange fibroblasts [population doubling level (PDL) = 20 to 30] aged fibroblasts (PDL greater than 40] were larger in size in terms of protein and RNA per cell, generally proliferated more slowly, exhibited different steady state [3H] proline transfer RNA (tRNA) precursor pool specific radioactivities, synthesized collagen at a substantially lower rate, and exhibited a reduction in the percent commitment to collagen synthesis. Total protein synthetic rates were reduced slightly in aged versus midrange fibroblasts but the difference was not statistically significant. Proliferative capacity (PDL/wk) correlated better with these changes than cumulative PDL. Cell size (protein/cell) was the variable that had the highest correlation with the reduction in collagen synthesis observed in human lung fibroblasts. Thus, an important differentiated function of human lung fibroblasts, collagen synthesis, is greatly diminished in vitro in large, slowly dividing fibroblasts.