The Hayflick Limit Tells Our Cells When to Die. Here's Why That's a Good Thing

Sam Westreich, PhD

Telomeres, the Hayflick limit, and how we may someday overcome the mortality of our cells
This picture is, apparently, a metaphor for “growth.” And it has cells in it! Double win!Photo by Suzanne D. Williams/Unsplash

Nothing lasts forever, thanks to entropy. Everything that grows, will eventually get old and die. Even our cells will eventually stop reproducing…

…or will they? Can individual cells keep growing and replicating forever? Is it only the larger organism that ages, or do we see old age taking effect down to the level of individual cells?

If you take a small tissue sample from an elderly man, are the cells themselves elderly? Or is aging a higher-order effect that appears due to a lack of cohesion and cooperation from the different cells over time?

The answer was discovered in part thanks to an American anatomist named Leonard Hayflick, in 1961, resulting in a rule in biology that bears his name: the Hayflick limit. Overcoming this limit may be a critical step in extending our lifespan, if we want to surpass our natural age limits.

Here’s what Hayflick discovered, and what it means for us today.

Do cells live forever?

In the early 20th century, the establishment view of vertebrate cells is that they could live forever, given the right conditions. As long as a culture of vertebrate cells received adequate nutrients and were kept in the right conditions, they would keep living, growing, and replicating for years (decades, centuries?).

This claim was supported by Alexis Carrel, a surgeon and Nobel Prize recipient for his work in vascular sutures. (Normal stitches can cause additional tearing when trying to reattach a severed vein; Carrel created a unique triangle-shaped, three-pointed suture approach that could successfully reattach blood vessels.)

Carrel was also interested in cell senescence, or aging. To support his claims that cells were immortal, he had a culture of chicken heart cells, kept inside a glass flask, that had been growing for 34 years — despite the lifespan of a chicken only being 5–10 years.

But this experiment didn’t stand up to scrutiny; others weren’t able to replicate it. Later, Hayflick and a colleague, Paul Moorhead, challenged Carrel’s claim.

Cells can only divide a limited number of times, Hayflick and Moorhead argued. Their experiments showed that cells from an organism could only reproduce a limited number of times, usually between 40 and 60 times, before they would no longer divide; they had become senescent (old).

This limit was later named after Hayflick, and holds true in biology today. For most human cells, the Hayflick limit is around 72 replications.

This means that, for most of the cells making up your body, they are 72 generations or fewer removed from the original first cell of your body, the fertilized egg cell that eventually grew into you.

The Hayflick limit is based on telomeres, sequences of junk, repeating DNA that are at the ends of our chromosomes. Whenever one of our cells divides, the cellular machinery needs to attach to the end of a chromosome to begin copying it — and the place where it attaches is not copied over. Telomeres serve as an attachment point, and are lost over time.

Eventually, after enough replications, the telomeres are too short to allow the DNA-copying machinery to attach, and the cell can no longer split into new daughter cells.

What about Carrel’s chicken cells? How did they live so long?

Even though the Hayflick limit is accepted, what was going on with Carrel’s chicken heart, that he kept alive for more than 30 years? How did those cells keep growing, if they should have stopped once the telomeres got too short?

There are a couple of theories:

Theory 1: adding new cells. Carrel provided a daily liquid supplement to the cells, to ensure that they had adequate nutrients. This culture was likely derived from chickens, and may have contained new cells that were able to latch onto the existing structure and grow.

Thus, it’s possible that, even though the original chicken heart cells were long gone, they were being constantly replaced by new cells in the nutrient solution, giving the illusion of long-living cells.

Theory 2: pluripotent stem cells. There is one major exception to the Hayflick limit, and that is stem cells. These cells express an enzyme, called telomerase, that is able to extend the shortened telomeres. Stem cells are mainly present in embryos, and usually eventually turn into specific cell types (with the aging limit in place), such as skin cells, organ cells, or muscle cells.

If Carrel’s experiment began with stem cells that would have become heart muscle in the future, they might have had active telomerase, and thus maintained long telomeres, unlike how normal cells would run out of telomeres.

In either case, other researchers were unable to replicate Carrel’s results, and the eventual consensus was that Hayflick and Moorhead were right: cells are not immortal, but have a limited lifespan, measured by the length of their telomeres.

What does this mean for us living forever?

So, bad news: aging is programmed into us at the cellular level. Even if we focused on a single cell in our bodies, that cell will eventually run out of telomeres and stop replicating… right?

There are some exceptions. Consider our blood, for example. How can we keep producing more red blood cells, if cells can only divide a limited number of times?

And what about skin? How can we always regrow skin over cuts and scrapes, if cells cannot replicate indefinitely?

The answer, in both cases, comes back to stem cells. Even as an adult, we have reservoirs of stem cells that are able to get around that Hayflick limit, thanks to their telomerase enzyme extending out their telomeres. When these stem cells divide, one daughter cell becomes a new stem cell, continuing the line — while the other daughter cell will differentiate, turning into a specific tissue type.

Additionally, even though our differentiated cells can only divide about 72 times, not all the cells in an area of our body are at the same number of divisions. In a section of our liver, for example, some cells may be on division 72, while others are only on division 40 or 50, creating mosaicism. This may help with restoration of damaged or aged organs; even in the adult, some cells can still divide a few more times but hold that ability in reserve until it’s needed.

This discovery also opens up a new line of inquiry for longevity: could we take telomerase as a supplement and live forever?

Unfortunately, it’s probably a bad idea, for a couple of reasons:

  1. Telomerase isn’t naturally transferred across cellular barriers, so taking a supplement of the enzyme doesn’t mean that it will actually reach all of your cells.
  2. Most of our aging problems are not due to us running out of cells, so boosting their ability to replicate doesn’t mean that they’ll solve the major issues of getting old.
  3. If we introduce telomerase willy-nilly, we could lead to unexpected, uncontrollable cell proliferation. There’s another name for this: cancer. We don’t want to lead to unwanted overgrowth.

In fact, a good amount of current telomerase research is focused on turning off the enzyme, to shut down cancerous tumor growth. We want less of it, not more!

In summary: our cells’ replication is limited, and that’s a good thing

The Hayflick limit is the result of a researcher challenging the dominant belief that cells are immortal and can reproduce an unlimited number of times. Leonard Hayflick showed that most of our cells cannot divide forever, and are limited due to the shortening of their telomeres each time they split.

This limit isn’t insurmountable — with the telomerase enzyme, stem cells can rebuild/regrow their telomeres to keep dividing forever — but it’s a good thing, and we want it in place. After all, uncontrolled, eternal replication is a primary driver of cancerous tumor growth!

If we want to live forever, we’ll need to make sure that our tissues are able to replace damaged organs and cells, but we don’t just want to flip the switch on unlimited growth. The Hayflick limit helps us understand which cells can live forever — and which should have a limited lifespan.

And if you see a supplement advertising that it helps lengthen telomeres, stay away!

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A microbiome scientist working at a tech startup in Silicon Valley, Sam Westreich provides insights into science and technology, exploring the strangest areas of biology, science, and biotechnology.

Mountain View, CA

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