The Hayflick Limit: why humans can't live forever

 A scientific legend, Leonard Hayflick, passed away at the beginning of August. Most non-scientists probably don’t recognize his name, but he made a remarkable discovery in the early 1960s. Back then, while doing experiments on human cells, he and a colleague, Paul Moorhead, discovered that our cells can only divide a limited number of times.

This discovery, although made at the level of an individual cell, has a dramatic implication: humans cannot live forever.

What Hayflick discovered was that after 40 to 60 rounds of splitting in two, cells simply won’t divide any more. At that point, they enter a phase called senescence, and they eventually die. The number of divisions that a cell can go through is now known as the “Hayflick limit.”

Prior to Hayflick’s experiments, many scientists believed that cells could divide forever. After all, every cell in our body comes from one original cell, and that cell came from our parents, and from their parents before that, and so on back through the ages. So it stood to reason that cells could continue to divide without limit. What’s more, in the early 20th century, Alexis Carrel (a Nobel laureate) claimed to have grown cells in his labs that continued to divide for decades, with no sign of decline.

(Aside: Jan Witkowski explained in an article back in 1980 that it was likely that Carrel’s seemingly immortal cells had been quietly replenished, without Carrel’s knowledge, by members of his lab who were eager to keep the boss happy.)

Back to the Hayflick limit: because all of our organs are destined to wear out, our bodies will simply die unless we can intervene and restore cells to their youthful state. That would require technology that has not yet been invented. Hayflick himself estimated that the limit of the human lifespan is 125 years.

Hayflick’s limit raised an intriguing puzzle: how does a tiny, microscopic cell keep track of how many times it has divided? In other words, how can a cell know how old it is? Don’t all of our cells have identical DNA? Hayflick himself didn’t have a solution for this, but a few decades later, others figured it out.

The answer to this cellular “clock” puzzle resides, it turns out, in our DNA. More specifically, it depends on the DNA sequences at the very ends of our chromosomes, which are called telomeres.

Telomeres don’t really do anything, and they appear very simple: they consist of a long stretch of six DNA bases, TTAGGG, repeated hundreds of times, end-to-end. All our chromosomes end with telomeres, on both ends.

So here’s the thing: when a cell divides, it has to copy all of its chromosomes. The mechanism for copying isn’t quite perfect, and it can’t go all the way to the end of the chromosome, so the new copy is a little bit shorter. The telomere gets shorter! Fortunately, we have a special enzyme, called telomerase, that fixes this problem by adding a few extra copies of TTAGGG to the end of each chromosome, restoring the proper length. Problem solved, right?

Well, no. Telomerase doesn’t work perfectly, and chromosomes sometimes do get a bit shorter each time they divide. When the chromosomes get too short, the cell can’t divide any more, and it eventually dies.

And yes, scientists have explored the question of whether telomere length might be the key to longevity. No one has figured out a way to keep telomeres long, and it’s not clear that would help anyway. On the contrary, as my Hopkins colleague Mary Armanios reported in a study last year, long telomeres might help individual cells stick around, but they don’t seem to prevent aging.

Does the Hayflick limit mean we really can’t live forever? Well, not necessarily. Some types of stem cells can produce “fresh” cells that could, in theory, replenish our old cells. Perhaps some day we’ll have the technology to replace our organs with new ones, possibly grown in a lab, that will have the youth and energy of a 20-year-old. But without replacing our parts, we are destined to wear out, even if we manage to avoid cancer, infections, and the many other perils that humans face.

Leonard Hayflick made it to 96, a ripe old age by today’s standards. It would have been fitting if he’d reached 125, the limit that he estimated, but no human has ever done that. Yet.