Evidence Against Somatic Mutation as a Mechanism of Clonal Senescence
In order to carry out complementation tests of the somatic cell mutational theory of clonal senescence, methods were developed for the isolation of proliferating hybrid and parental tetraploid human cells which would not depend upon biochemical selection. Crosses between short-lived strains resulted in short-lived offspring and crosses between long-lived parents tended to be long-lived, in experiments involving skin fibroblast-like cells. Crosses between strains of contrasting longevities gave growth potentials approximately intermediate to those of the parentals.
Crosses were also carried out between euploid fibroblast-like cells and two other distinctive euploid cell types (“E,” or epitheloid and “AF,” or aminiotic fluid cells, both derived from second trimester aminotic fluid) (Hoehn et al., 1974), and both having replicative life spans which are much more limited than the fibroblast-like skin cell (“F” cells). Compared to F x F tetraploids, F x AF and F x E hybrids had lesser growth rates, but were superior to those of parental AF and E cells.
The results are interpreted as evidence in favor of a programmed mechanism for clonal senescence and against somatic cell mutation, at least for the case of mutations involving single copy DNA.
KeywordsHybrid Clone Werner Syndrome Mitotic Cell Cycle Hybrid Tetraploid Replicative Life Span
Unable to display preview. Download preview PDF.
- 2.T. H. Norwood, Somatic cell genetics in the analysis of in vitro senescence, in:“Genetics of Aging,” E. L. Schneider, ed., Plenum Press, New York (1978).Google Scholar
- 10.R. DeMars, Somatic cell mutations and cellular senescence, in: “Senescence Dominant or Recessive in Somatic Cell Crosses?” W. W. Nichols and D. G. Murphy, eds, Plenum Press, New York (1977).Google Scholar
- 11.S. Ohno and Y. Nagai, Genes in multiple copies as the primary cause of aging, in: “Genetic Effects on Aging, Birth Defects, Orig. Art. Series,” Vol. XIV, Alan R. Liss, New York (1978).Google Scholar