6 replies to this topic

[manofsan]

I was reading about HeLa cells, originally taken from the cervical cancer of Henrietta Lacks:

http://en.wikipedia.org/wiki/HeLa_cell


So can these cells go on propagating endlessly, purely based on telomerase suppressing the Hayflick limit?

And yet they are described as uncontrollable. Is the only way to be immortal, to be so rampantly proliferative so as to be inherently malignant?

Are HeLa cells out-distancing the glycosylation, methylation, and related aging effects though sheer speed of multiplication?
I guess with an in vitro sample one doesn't care about defective daughter cells, since any duds would fall by the wayside, while the question of malignant mutations doesn't arise since the main culture is already malignant anyway.

Hmm, so if rapid proliferation is answer, how does one do that while dodging uncontrollable malignancy?

[spiritus]

I think rejuvenation then malignancy will be the first way of going about it. Perhaps later we will make the advances in rapid proliferation.

i think

[manofsan]

Is the only way to be immortal, to be so rampantly proliferative so as to be inherently malignant?

When a cell becomes malignant, it dedifferentiates into a stem cell-like stage whilst ignoring the control messages emanating from its environment. Picture it like a rebel stem cell. It is still able to organize a vascular system to feed its growing numbers, arrange itself in sophisticated three dimensional structures and listens to its own control messages.

The answer is no. In the lab, cells can become immortalized without losing their ability to listen to control messages.

Hmm, so if rapid proliferation is answer, how does one do that while dodging uncontrollable malignancy?

The same way your body does it now, replenishing the lining of your gut, once every 24 hours. Stem cell niches exist for every cell type in your body, and each one is designed to replenish cells lost either by injury or aging. For as yet not understood reasons, however, the capacity for these niches to operate declines dramatically after a certain stage until the rate of cell loss/senescence overtakes the rate of replenishement.

Thanks -- alright then, how come Henrietta Lacks' cells have not lost their ability after umpteen number of replications? When we say that these niches lose their ability to operate after a certain stage -- is it the immortality that's most most adversely affected or is it the control that deteriorates the most?

What is the chief contributor to the Hayflick limit being at 52 replications, and what is the main reason why all our cells don't replenish every 24 hours like the lining of our gut? Too much energy required, too much risk of cancer?

Has the Hayflick limit ever been artificially elevated in test animals, and has this ever led to increased lifespan?

[John Schloendorn]

how come Henrietta Lacks' cells have not lost their ability after umpteen number of replications?

Because as the wiki entry says she had cancer, and they took them from the cancer. Or am missing the point of the question?

Has the Hayflick limit ever been artificially elevated in test animals, and has this ever led to increased lifespan?

Note that the "Hayflick limit" is referring specifically to fibroblasts in culture and can thus not be elevated in an animal. It can be done in culture, e.g. by administering telomerase protein. It is indeed accepted that the selective pressure that forged this and similar replication control mechanisms is tumor suppression [1].
Telomerase overexpressing mice should come close to what you mean. In a nutshell they regenerate better, get more cancer and die a little earlier [2]. But on the other hand, mouse telomeres are very long, so that much of these effects might be attributed to a telomerase signaling function, rather than its well-known catalytic activity. In humans the result might look different.

[1] Campisi J. Aging, tumor suppression and cancer: high wire-act! Mech Ageing Dev. 2005; 126(1):51-8.

[2] Cheong C, Hong KU, Lee HW. Mouse models for telomere and telomerase biology. Exp Mol Med. 2003 Jun 30;35(3):141-53.

[Mind]

I would tend to think our cells accumulate damage from day one of our life. A lot of the damage is caused by metabolism, which starts at day one. There are also many environmental factors that contribute to cell damage (basically, from day one). So we are accumulating damage (and undigested/undisposed junk) througout our entire life, yet the classic signs of aging do not begin until after puberty. It is as if our "growth program" is stronger (more relevant) than damage accumulation during the first few years of our life. I would say this lends credence to manofsan's idea that the rapid replication of cancer cells prevents them from feeling the effects of aging. Let us say we could keep a group of cancer cells alive in a lab or on a host for a couple decades. I would think they would suffer the same aging related damage (metabolism-related and environmental) as regular cells.