POTENTIAL ROLE OF ANTIONCOGENES IN AGING

Some observations on cellular senescence are discussed regarding the possibility that the postulated genes, which bring about the DNA synthesis block of senescent fibroblasts, might be similar to those designated as anti-oncogenes or tumour suppressor genes. The latter genes have been defined by tumorogenicity tests of hybrids from fused tumour and normal cells, of which the retinoblastoma (RB) gene is a prototype. Similarities between the two systems are considered, which are consistent with the assumption that senescent growth arrest, like the suppression of tumorogenicity of the hybrids, might be effected by anti-oncogenes via inhibition of cellular oncogenes in their growth signal transduction functions. A link may be provided by the finding of a direct interaction of certain DNA tumour virus oncoproteins with the RB gene product p105-RB, together with observations that the tumour viruses are also able to reinitiate DNA synthesis in growth arrested senescent fibroblasts. The possibility is also discussed that some silent retinoblastoma-like genes might become aberrantly expressed in senescent cells owing to a progressive loss of 5-methyl cytosine residues of DNA. © 1990.