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This question relates to both immortal cells such as cancers and organisms like the Hydra genus. Isn't it technically impossible for these "immortal" biological systems to live forever, even disregarding accidents and disease?

I am aware that they are considered immortal because they do not exhibit the usual degradation of functionality as they chronologically age. In cancer's case an up regulation of telomerase prevents the usual gradual depletion of DNA at the chromosomal ends limiting a cell's lifespan. But at the same time cancer cells and immortal organisms still undergo DNA damage and thus mutation (cancer cells even mutate faster as far as I know), wouldn't the stacking of these mutations at some point kill off the cancer cell line/immortal organism as some vital part of their metabolism is inevitably damaged?

Wouldn't true biological immortality require an organism with DNA that is either impossible to damage or if it could would always be perfectly repaired? (creating an evolutionary dead-end as well)

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    $\begingroup$ It sounds like you're actually defining immortality as perfect self-replication. With that definition, yes, it's practically impossible, as no DNA replication machinery is perfect. Is it a rhetorical question? :) $\endgroup$
    – Roland
    Commented Mar 1, 2017 at 21:07
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    $\begingroup$ @Roland It wasn't intended as a rhetorical question hahah, I'm just wondering if I'm missing something obvious. I read about achieving human biological immortality by engineering up regulation of telomerase and this question popped in my head as a caveat to human immortality. $\endgroup$
    – Koen vd H
    Commented Mar 1, 2017 at 21:25
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    $\begingroup$ Keep in mind that all living things are the result of an unbroken chain of replications going back to the first cells. If "immortality" is defined to include "the ability of cell lines to replicate indefinitely" (and if we bring in the "immortality" of cancer cells, then it is) then all evidence points to biological immortality being possible - I mean, not really, the heat death of the Universe will get us if nothing else does, but 3-odd billion years isn't a bad run so far. This is different of course from the question of the immortality of any given multicellular organism. $\endgroup$
    – Oosaka
    Commented Mar 1, 2017 at 21:36
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    $\begingroup$ I don't think you're missing something. The word "immortality" is used to describe cell lines that have bypassed the normal replication limit of normal ("mortal") cells, but you're right it's technically not true. If you culture a cancer cell line for a very long time, it will degrade in various ways and at some point it will stop growing and die. $\endgroup$
    – Roland
    Commented Mar 1, 2017 at 21:38
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    $\begingroup$ I think part of the confusion between where your question wants to be and a purely rhetorical question is that there are two different types of immortality here: perpetual life of an organism, like a human - who contains many cells that proliferate and die all the time, and immortality when referring to lines of cultured cells: the definition of an immortal cell line is a line which will not stop replicating due to intrinsic mechanisms to limit cell division. (edit: while typing this comment @Roland commented effectively the same exact thing) $\endgroup$
    – Bryan Krause
    Commented Mar 1, 2017 at 21:42

2 Answers 2

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Good question.

There are many organisms that are technically biologically immortal. However, I would like to point out that the definition of biological immortality is this:

...cells that are not limited by the Hayflick limit, where cells no longer divide because of DNA damage or shortened telomeres.

(That's from here.)

So biological immortality doesn't really cover disease or physical trauma, which would actually include damage to DNA. I know what you're thinking: But wait, doesn't biological immortality literally mean cells that don't die because of DNA damage? Nope. Close, but no. Look back up at the definition. You probably caught it this time (by the way, it's not listing two different reasons (DNA damage and shortened telomeres), just rewording the Hayflick limit (DNA damage aka. shortened telomeres)). Biological immortality does not mean that the cell will not die because of excessive mutation (which would fall under physical trauma mind you, be it from chemicals, radiation, or just plain mistakes during replication), it means that the cell will not die from excessive programmed mutations, aka. its Hayflick limit, aka. telomere degradation. A molecular biology course summary from Berkeley says:

However cells that express telomerase still undergo cellular senescence in response to DNA damage, oncogenes, etc.

Ok, sidetrack time (go ahead and skip this part if you already know what telomeres are). A telomere is a repeated DNA sequence at the end of a chromosome that protects the coding regions from deletion (the reason for these deletions is complex and off topic, but long story short, RNA primers cannot attach to the very end of a chromosome, so a little of the lagging strand is lost during every replication). So the telomere takes the hit instead of the important coding DNA further up the chromosome (see this article.) As you can imagine, there is only enough telomere to go around, so cellular aging exists unless the organism has active telomerase, which is an enzyme that adds telomeres every time they are lost (see this article).

So, short answer, biological immortality is very possible in its actual definition (see above).

Concerning your definition (immortality regarding all mutations, programmed or otherwise), an organism comes to mind: Physarum polycephalum. It is biologically immortal in the way we have just defined, but also avoids DNA mutation by sharing DNA (constantly comparing and fixing sequences) among thousands to millions of nuclei through homologous recombination, which repairs DNA mutations at a freakishly high efficiency when you include millions of strands bearing what should be the same sequence (see this article). Physarum polycephalum is a slime mold, meaning that when cells meet each other, they fuse. This particular slime mold actually prefers to be a plasmodium, which is a constantly growing mass that is technically a multinucleated single cell but can grow to be potentially infinitely large as far as we can tell. Because of its extreme ability to correct mutations, this organism has been referred to as, exactly like you said, an "evolutionary dead-end." I'm sure it still sustains some mutations over a very long period of time, but you might want to check it out nevertheless.

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    $\begingroup$ Nice answer, +1! I recommend that you add some more references in the answer, like about telomeres and Physarum, etc. $\endgroup$ Commented Mar 2, 2017 at 7:50
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    $\begingroup$ Thanks, I do find it a bit weird that aging in this context is solely defined as shortening telomeres instead of overall DNA damage. Also that mold seems fascinating. $\endgroup$
    – Koen vd H
    Commented Mar 2, 2017 at 8:48
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    $\begingroup$ @another'Homosapien' Thank you. Done. And thanks for the italics, not sure how I missed that... :) $\endgroup$
    – CDB
    Commented Mar 2, 2017 at 20:50
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    $\begingroup$ @KoenvdH My pleasure :) Keep in mind, that's just the definition of cellular senescence (aging). While we're pretty sure it has a lot to do with the aging of the whole organism, we still don't know for sure if that's the entire story. But alas, that is a discussion for a different question. To avoid confusion, slime molds are very inaccurately named; they are actually protists. They were named when we still thought they were fungi... But yes, they are quite fascinating. :) $\endgroup$
    – CDB
    Commented Mar 2, 2017 at 20:58
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The whole "science" behind telomeres is rather flaky, for example:

Is Telomere Length a Biomarker of Aging? A Review

Although telomere length is implicated in cellular aging, the evidence suggesting telomere length is a biomarker of aging in humans is equivocal...

They observed that the change in telomere length at follow-up was highly variable with some participants showing an increase in telomere length.

So like most questions in biology, there's no answer.

Also P. Physarum has many strains, it is in no sense an "evolutionary dead end" simply because it can't mutate.

http://www.genetics.org/content/78/4/1051.short

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    $\begingroup$ "There is no answer" is not an answer. A more accurate description of your situation would be "I do not know the answer, nor do I care to seek one out." In which case, it would be better to not answer at all. Regarding your links, see my answer. I said nothing of mortality rates, like the article you cited was discussing. Rather, I was speaking purely of cellular senescence, which was the OP's question. The correlation between telomere degradation and mortality rates has so many variables (disease, trauma, lifestyle, etc.) that it is very difficult to substantiate, as we see in that article. $\endgroup$
    – CDB
    Commented Mar 2, 2017 at 21:34

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