Understanding the Hayflick Limit, part 2

Telomerase makes new DNA from an RNA template

Last time, we started into telomeres, and I hinted at the function of telomerase.  Telomerase is an enzyme found in most organisms that adds bases to the ends of your chromosomes, extending the “aglet” (telomere) of the chromosome.  It does this in a rather startling way… it has its own RNA sequence that it uses as a template for making new DNA.  This is startling, at least to a virologist, in that it’s very much like what a retrovirus does.  Telomerase is considered a reverse transcriptase, meaning it takes an RNA template and makes complementary DNA from it.  This is opposite from the usual flow of information in the cell  (DNA –> RNA –> protein).  In the case of telomerase, what is copied is a simple motif of a a few bases repeated many thousands of times in a row.

Normal embryonic cells have active telomerase, as do some adult cells that have to divide often, like white blood cells.  Most cells, though, have their telomerase gene “shut off” so that no more can be made.  Remember that every time a cell divides, those telomeres get shorter by a few hundred bases, eventually getting too short to hold the ends, and the chromosome becomes unstable.  There are some diseases that result from premature shortening of the telomeres (Werner syndrome), and the patients have signs of premature aging (“progeria”).

The idea that the upper limit of our lifespan (“cellular senescence”) is somehow tied to a single biological phenomenon is intriguing.  If you, dear reader, immediately begin wondering whether this ticking clock can be silenced, or turned back, you are not alone.  I imagine every young scientist first learning about telomeres and telomerase imagines themselves as the saviors of mankind, or perhaps fulfilling the lines of the “Necronomicon”:

Cthulhu: telomerase positive

That is not dead which can eternal lie.
And with strange aeons even death may die.

So why can’t we just “turn on” the telomerase activity and stop the inevitable shortening of telomeres which causes cellular replication to fail in the elderly?  It has to be pointed out that some organisms do not succumb to senescence, and they are essentially immortal, although none of them are smart enough to clean up on long term, low risk investments.  Key examples are lobsters, jellyfish and coral.  Lobsters in particular are interesting because they have active telomerase throughout their lifespan, and they actually appear to be more fit the older they get.  That subject is a riddle that, so far as I know, remains unsolved.

Why do we poor mammals have to be content with a scant 100 or so years of life?  Why can’t we, like the lobsters, live forever?  The answer lies in one word:  cancer.  Cancer is built in to our biology.  Any system that requires exquisitely tight controls will eventually fail.  If that system governs the rate at which cells grow and divide, you will eventually have out of control growth.  The longer you walk this tight rope, exposed to mutagens in the air, the soil and the water, the greater the risk of failure.  Telomere shortening may have evolved as a way of keeping cancer in check, eliminating older cells that have been exposed to DNA damaging conditions.  Turn telomerase back on, and those geriatric cell lines will continue to accumulate damage, increasing with each division the chance of cancer developing.  It may not be a coincidence that the immortal animals live in dark oceans where UV damage is minimized.

Cruz Hernandez: 128 yrs old at death

That’s the cellular evolutionary view of senescence.  The organismal evolutionary view is more intuitive.  If old animals never die, and the number of animals that can be sustained in an ecosystem never changes, then the larger, older animals would outcompete the young, smaller animals for food and resources.  With no new generations, the gene pool becomes very static and the diversity remains low, making the population susceptible to pathogens.

“Futurists” like to talk about when the first immortal human will be born.  But I agree with Dr. Hayflick on this:

“When it becomes possible to slow, stop, or reverse the aging process in the simpler molecules that compose inanimate objects, such as machines, then that prospect may become tenable for the complex molecules that compose life forms. “

The concept of an immortal human with active telomerase ignores the central fact that older cells develop cancer.  Any proposal to immortalize humans must be prepared to deal with the escalating cancer and disease risk.  Aging and senescence are not just a matter of allowing cells to continue replicating.  It is dealing with the inborn errors of metabolism and biology.  As Dr. Hayflick suggests, if we can’t stop simple machines from breaking down, what hope do we have to prevent the same process in the very complex machine that is a human?

In a future post, I hope to explore those rare human cells that have achieved immortality as transformed cultures.

3 comments on “Understanding the Hayflick Limit, part 2

  1. Now, I spend most of my time attempting to dissuade my friends of their futurist leanings, as while I find transhumanism an appealing concept I am at heart a pessimist. However, you write this article from the perspective that active telomerase is being considered in a vacuum, as a kind of “magic bullet” that will end aging with no further repercussions, but that’s not really the case outside of the loony-fringe of the loony-fringe, like Kurtzweil. The material I’ve read on the subject from people like Aubrey de Grey, while they require a small sack of salt, discusses the topic in terms of multiple integrated treatments which will each, in some small or large way, extend lifespan, which will eventually lead to a stage where the existing set of treatments allows an individual to survive long enough for the next set of treatments to be developed and implemented.

    That outlook is, if still extremely speculative, substantially more plausible than “turn on telomerase, live forever”.

  2. I am coming to the opinion that organismal aging (which differs from cellular aging) must have more to do with accumulated epigenetic changes than it does with length of telomeres. It would be interesting to see if animals with known longevity (e.g. Bowhead whale, Galapogos Tortoise, Rougheye Rockfish) have diets rich in methyl groups.

    Mutations matter, but epigenetics matters more.

  3. The organismal evolutionary view of aging seems extremely redundant, and is in many ways a form of group selection. Rather than populations being selected for which ones allow the young adults to dominate so as to promote genetic diversity, it seems more reasonable to speculate that it is merely an issue of bioeconomics. For example, the Hayflick quote argues that there are so many problems to be solved in the case of aging, and that this is probably the major obstacle in preventing it. This being the case, it could potentially be that genomes that didn’t invest in maintaining the original organism, but rather focused on reproduction would be favoured. This would only be the case, of course, if it is more economically viable to build a new body as opposed to maintaining an old one. This is certainly not my area of study, so please point out any flaws in my reasoning.

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