Age-related changes in the mitogenic activity of heparin-binding growth factors in rat sera

Sera from rats of either sex and different ages were examined for their ability to stimulate DNA synthesis in BALB/c 3T3 cells. The activity levels of sera from male and female rats were almost the same, with age-related changes in activity also being quite similar. Activity was considerably higher in infant rats (1-month-old), but then, at a young age (6-7 months), decreased drastically for male rats, but not significantly for female rats. It increased again in middle-aged rats (12-13 months old) and was maintained at the same level toward old age (24-26 months old) for both sexes. In order to determine what kinds of growth factors were responsible for these changes, we carried out heparin affinity chromatography on the sera of male rats. Four peaks were obtained for all sera, with individual peaks exhibiting specific age-related changes in activity. Among them a peak which was eluted at 1.1 M NaCl had very high activity. It showed a similar age-related change to that of the whole sera, except for a significant increase at old age, and the factor(s) included in the peak was found to be derived from platelets. These results suggested that the factor(s) in the peak was responsible for maintaining serum mitogenic activity at an old age. The experiments undertaken to characterize this factor suggested that it is a novel one.