Dysdifferentiative nature of aging: passage number dependency of globin gene expression in normal human diploid cells grown in tissue culture.

Aging may be a result of cells drifting away from their proper state of differentiation. This process has been called dysdifferentiation. Normal diploid cells grown in tissue culture conditions undergo numerous biochemical and morphological changes and have a finite division potential. These changes could be a result of such a dysdifferentiation process. Changes in the differentiated state of a cell are frequently manifested by the expression of genes that are normally repressed. Previous studies have shown about a two-fold age-dependent increase of alpha and beta globin-like RNA in mouse brain and liver tissues. Therefore, the possible presence and increase of globin RNA was investigated in the nonerythroid human diploid strain WI-38 grown in tissue culture as a function of population doublings. A DNA X RNA hybridization technique using specific complementary DNA (cDNA) to alpha and beta human globin was used to detect possible complementary RNA sequences in total cellular RNA preparations extracted from cells at population doublings of 26.4 and 46. No globin-like RNA sequences could be detected above background noise levels for either of these two passage numbers. Thus, the globin RNA genes appear to be highly repressed and this degree of repression maintained as the culture approaches its characteristic population doubling limit.