IN MEMORY OF DR. ROBIN HOLLIDAY, HIS LABORATORY IN MID-NINETEEN EIGHTIES, AND TESTING DNA METHYLATION THEORY OF IN-VITRO CELLULAR AGING

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Robin Holliday, a noted British philosopher and a sculptor, born in 1932 died in 2014. After his remarkable contribution in nineteen sixties and seventies to modern molecular biology through his presentation of a genetic recombination model, i.e., Holliday model, and his proposal of epigenetic control mechanisms based on DNA methylation, he poured in nineteen eighties his scientific interests in the mechanisms of aging, particularly in solving the problem of in-vitro limited proliferative lifespan of cultured human diploid cells (HDCs). Two major findings obtained during that time in his laboratory were that cell’s memory of proliferative life span can be modified with a pulse treatment of DNA-methyl transferase inhibitors, 5-azacytidine and 5-azadeoxycytidine, and that SV40-infected-, but not immortalized, HDCs maintain their level of DNA methylation until the end of their proliferative life span. It was shown with these two lines of findings that the drift of DNA-methylation level is influential, but not essential determinant of the limitation of proliferative potential. These studies underlay further studies of Hayflick limit in nineteen nineties including the discovery of telomerase participation.