101 Facts About Ageing #23: Telomere Shortening And The Hayflick Limit

As Daniel Patrick Moynihan, an American sociologist, politician, and diplomat once said: “Everyone is entitled to his own opinion, but not his own facts”. And we wholeheartedly agree. A shared set of facts is the first step to building a better world with longevity for all. In that spirit, we are creating a series that covers 101 indisputable facts about ageing, health and longevity.

A human being’s body experiences about 10,000 trillion cell divisions in a lifetime. Each division involves the near-perfect replication of the cell’s DNA. However, the molecular machinery that carries out this copying cannot quite replicate the entire length of the DNA strand, meaning that a portion of the DNA at the end of each chromosome is lost each time the cell divides. Telomeres are sequences of repetitive, non-coding DNA that protectively cap the ends of the chromosomes, providing a temporary solution to this problem. When a cell divides and its DNA is copied, a section of the DNA is lost from the ends of the telomeric regions instead of the regions containing genes essential for life.

Every time the cell divides and DNA replicates, the telomeres will become shorter and shorter. In some cells, an enzyme called telomerase is able to repair these telomeres, but the majority of normal mammalian cells do not express telomerase, meaning that telomeres will continue to shorten until further replication risks eating into the genetic code. To prevent this from happening, cells will usually stop dividing when their telomeres become too short (this is called replicative senescence) or ‘commit suicide’ (apoptosis). This replication limit is called the Hayflick limit and occurs in most human cells after around 40 – 60 divisions, at least in cells cultured in the lab.

It is still a matter of debate whether the Hayflick limit is as important in ageing living organisms as it is in cell culture, since these two environments are very different and have substantial effects on how cells behave. Shortened telomeres are correlated with increased mortality risk in humans, and mice genetically modified to have longer or shorter telomeres have longer or shorter lives, respectively. However, mouse cells have longer telomeres than human cells, yet have a smaller Hayflick limit (around 20 divisions). Bowhead whales, the longest lived mammals, have a Hayflick limit of 80+ divisions.