Hayflick’s handy guide to immortality and cell senescence

Hayflick L, Moorhead PS. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585-621. doi: 10.1016/0014-4827(61)90192-6.

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Before the 60’s, Alexis Carrel propagated the idea that cells could be grown forever. Carrel was famous for allegedly maintaining chick cells in culture for over 34 years, but no one could replicate this.

Leonard Hayflick observed that his cells were not immortal. They eventually stopped dividing and ultimately became senescent. After several experiments, Hayflick and Paul Moorhead theorised that cells have three phases of growth. Most important of these was Phase III. The cells would enter Phase III after 40-50 divisions, where they would stop dividing. This was later named the Hayflick limit. A pivotal experiment was one were they mixed old male cells with young female cells. When they checked back much later, only female cells remained. This meant cells could track their own age, and ruled out external factors as causes of senescence. Further experiments found that frozen cells could remember how old they were once they thawed out. This kickstarted the idea of a “replicometer”, something within cells that was counting their age not by the passage of time, but by the number of cell divisions they had undergone.

The search for this “replicometer” involved several discoveries coming together. After learning of Hayflick’s findings, Alexey Olovnikov proposed that cells could not completely replicate their DNA at the chromosomal ends. This would shorten the cells’ DNA, eventually damaging genes, but what was stopping genes from being damaged after just a few divisions? Telomeres, nucleotide sequences at the ends of chromosomes, turned out to be protecting genes. Telomeres were being shortened as the cell divided, hence telomeres were the “replicometer”. Immortal cells like stem cells and cancer cells could escape senescence because they expressed high levels of telomerase. Telomerase is an enzyme discovered by Elizabeth Blackburn and Carol Greider that elongates telomeres, granting the cell more divisions.

Unfortunately, living forever is not as simple as expressing more telomerase in our cells. The Hayflick limit is a way for cells to avoid mutations from excessive cell division. Research is being done, but immortality is still a pipe dream.

Creator: Jia Hao Beh

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