What is the status of the telomeres in HeLa cells?

Question

I read several times about the hypothesis, also reported on Wikipedia, that ageing is linked to the length of the telomeres. Each time the chromosomes are duplicated during a cell split the telomeres lose a little bit of their length and their ability to drive further duplications declines.

But now I read the story of Henrietta Lacks. Her cancerous cells where harvested 70 years ago and they have been used to create thousands of cell lines. Since she was 30 years old when the cancer was discovered those cells now might be 100 years old. The real age is probably less because most of them were frozen from time to time, but on the other hand they are cancerous cells duplicating at a frantic pace.

I read from this answer that cancer cells can activate telomerase and restore the telomeres, but is it still happening after so many years? In all the cultivations in vitro did were they always provided with the right nutrients to produce telomerase?

Is there a study on the status of the telomeres in those cells? Are they really "eternal" in practice or the definition of eternal is still in theory?

Answer 1

Wow. I looked this up on PubMed and there are 906 results for HeLa telomerase. Not all are real, but there's some data to work with here.

I've been reluctant to rely on Russian charity with the Cold War in full swing, so there are a lot of leads I won't follow in the abstracts that came up: Ivankovic, 2007 says "surprisingly, found that the fraction of cells that divided 0-1 time over 6 days in culture have several times higher endogenous telomerase activity than the fastest dividing fraction. Additionally, the non-growing fraction regains an overall high labeling index and low SA-beta-Gal activity when subcultured again." Varshney, 2014 wrote that "The overexpression of telomerase is not proportionate to telomere length in cancer cells, suggesting that the immortalizing phenotype can be mediated through other factors in addition to telomere length." Taji, 2017 reports that autophagy reduces the telomerase activity in HeLa cells. But TERT induces autophagy according to Roh, 2018, which describes the involvement of hexokinase 2 and glucose metabolism and more importantly is actually published in the sense of public.

Anyway, I eventually happened upon Nakashima, 2013 (open access) which says "the telomerase inhibitor BIBR1532 acts together with TEL patch mutations to inhibit the growth of HeLa cell lines and ... apoptosis is a prominent mechanism of death of these cells." (Without the inhibitor the cells seem to just make more telomerase until it works without the patch) I'm rather amazed that a veteran "cancer survivor" so to speak like HeLa will still undergo apoptosis if it runs into a telomere problem, but there it is!

Answer 2

First, I will address your misconception. You can interpret the telomere length of a typical somatic cell as its upper limit of remaining replication-cycles and therefore as an indicator of its age. This describes the fate of a cell, however, the age of a person should be seen as something else; when you are 20 years old, your cells don't have shorter telomeres than when you were half that age. Aging as a person is a complex topic with compound gradual influences e.g. loss of epigenetic memory, i.e. DNA and histone states, worsening of proteome health, i.e. worsening of protein homeostasis that eventually leads to cells not being able to cope with the required protein turnover leading to functionally ineffective proteins and accumulation of waste. DNA damage also plays a role.

To your actual question: HeLa cells can regenerate their telomeres with telomerases. This means that different HeLa cells within a flask will have telomers at different lengths. Most of your bodies cells do not have telomerase activity as it represents a huge risk for cancer. HeLa cells are enteral at least in the sense, that the cell-line will probably be conserved as long as there are humans or it is deliberately destroyed for political reasons. However, individual cells are not immortal, e.g. might die to external damage or mutations.