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Mortality and Immortality at the Cellular Level. A Review

L. Hayflick1

1University of California, San Francisco, P.O. Box 89, The Sea Ranch, California 95497 USA; fax: 707-785-3809; E-mail: hayflick.leonard@gene.com

Submitted August 1, 1997.
A brief history of cell culture as it pertains to aging research had it’s origins with the thoughts of Weismann and the work of Carrel. Until the early 1960's it was believed that normal cells had an unlimited capacity to replicate. Consequently, aging was thought to have little to do with intracellular events. In the early 1960's we overthrew this dogma after finding that normal cells do have a finite replicative capacity. We interpreted this phenomenon to be aging at the cellular level. In subsequent years the objective was to identify the putative cell division counting mechanism that had been postulated to exist. Efforts to achieve this goal have had a remarkable degree of success only in the last few years with the discovery of the shortening of telomeres at each round of DNA replication that occurs in normal cells both in vivo and in vitro. Immortal abnormal cell populations overcome telomere shortening by activating an enzyme, telomerase, that catalyzes the synthesis of the TTAGGG sequences that compose mammalian telomeres, thus maintaining their length constant. Telomere shortening in normal cells is not a chronometer because time is not measured but rounds of DNA replication are measured. I propose the term replicometer for the device that measures the loss of telomeric sequences in normal cells because the action is that of a meter, and it is counting DNA replications. Telomere shortening and the finite lifetime of normal cells is more likely to represent longevity determination than it is aging. The hundreds of biological changes that herald the loss of replicative capacity in normal cells are more likely age changes.
KEY WORDS: mortality, immortality, aging, longevity, cells, telomere, telomerase, replicometer.