Differences between transfer RNA methylase activity in human diploid fibroblasts during in vitro and in vivo aging

The change of the specific activity of S-adenosylmethionine: tRNA methyltransferase in cultures of human diploid fibroblasts at different passages has been measured and compared with that in the same type of cells derived from donors of different ages. Whereas the specific activity of tRNA methylase in the in vitro aged cells was found to decline gradually with increasing passage number of the culture, a different activity--age relationship was observed for this enzyme in cells derived from donors of different ages. The activity of tRNA methylase is high in the fetal cells and drops drastically in the "newborn" cells. After a further 10% decline, the activity of this enzyme reaches a steady low level in the postnatal cells from donors ranging in age from 3 months to 94 years. These findings cast doubt on the validity of the assumption that the results obtained from in vitro aging experiments reflect the biochemistry of aging in vivo. The "fetal" enzyme can methylate the "aged" tRNA but the "aged" enzyme cannot methylate the "fetal" tRNA. The fetal cells contain enzyme activities specific for the formation of m1A, m5C and m1G. These activities are low or deficient in "aged" cells. Control experiments showed that all of these results are due neither to the presence of inhibitor or stimulator in the extract nor to effects related to the population density, sex or growth rate of the culture.