Hayflick limit

The Hayflick Limit is a term used to explain cellular aging. Thanks to the Hayflick Limit and the research that followed, we now know that a typical human fetal cell will divide between 50 and 70 times before experiencing senescence, or the process by which an organism’s cells cease to divide.

The Hayflick Limit theory wasn’t always the widely held belief, however. Just like there was a time when the commonly held belief was that the world was flat, there was a time when it was believed that cells could infinitely replicate.

In early 20th century France, Alexis Carrel was a surgeon working on chick heart tissue. His experiments supported the theory of infinite replication. In particular, he showed that a strain of embryonic chick heart fibroblasts first established on 17 January 1912 was grown for thirty-four years. Although scientists tried again and again to repeat his findings, they couldn’t.

Still, if cells were immortal, wouldn’t people be, too?

The Hayflick Limit Theory and Vaccines

The Hayflick Limit Theory was developed in the 1960s partly because of the mission to develop untainted cell cultures for vaccines.

In the late 1950s, cell cultures from human cells were derived from animal cells and tumor cells, which offer cell lines that continue to divide. The polio vaccine, for example, used monkey kidney cell cultures instead of human tissues.

Some of the polio vaccines administered from 1955–1963 were found, in fact, to be contaminated with the simian virus 40 (SV40).

In 1961 Leonard Hayflick was working for the Wistar Institute in Philadelphia, where his role was to provide cell cultures to scientists. He was determined to do more: he wanted to figure out a way to generate non-cancerous human cell lines that could grow continuously in a lab.

That same year, with his colleague Paul Moorhead, Hayflick observed that cells do not replicate in cultures infinitely, but instead only a finite number of times. They described this phenomenon in the paper, “the serial cultivation of human diploid cell strains,” ultimately disproving Carrel’s theory.

Fetal Tissue and the Hayflick Limit

Still, Hayflick wanted to use fetal tissue cells for cultures because, according to his theory, they would be protected from outside pathogens and would be totally uncontaminated. At the time, however, abortion was only legal in certain cases, and fetuses were typically discarded as medical waste.

Then, in 1962, Hayflick received lung tissue from a legally aborted fetus in Sweden. With it, he established the WI-38 cell line, which became the first human diploid cell line to be used in human vaccine preparation.

In 1965, Hayflick further detailed the concept of the Hayflick Limit in cells in a paper titled “The limited in vitro lifetime of human diploid cell strains.”

The WI-38 cell line was fundamental to developing vaccines against polio, measles, mumps, rubella, varicella zoster (chicken pox), herpes zoster, adenovirus, rabies, and Hepatitis A, as well as in the production of many other early vaccines.

Why Do Cells Stop Dividing?

Later research by Russian Scientist A M Olovnikov explained the underpinnings of the Hayflick Limit and the discovery of in vitro and in vivo cell senescence without naming the theory. His research indicated that during mitosis, the ends of chromosomes did not replicate themselves.

Specifically, he proposed that:

“The length of telomeric DNA, located at the ends of chromosomes, consists of repeated sequences, which play a buffer role and should diminish in dividing normal somatic cells at each cell doubling.” (Olovnikov 1996)
“The loss of sequences containing important information that could occur after buffer loss could cause the onset of cellular senescence.” (Olovnikov 1996)
“For germline cells and for the cells of vegetatively propagated organisms and immortal cell populations like most cancer cell lines, an enzyme might be activated that would prevent the diminution of DNA termini at each cell division, thus protecting the information containing part of the genome.” (Olovnikov 1996)

As science continued to progress, most of his theories behind telomeres were authenticated.

These discoveries about the genetic structures related to the Hayflick Limit offer scientific insights into the mysteries of aging and lifespan.