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I've been doing some light reading on DNA damage theory of aging. One of the main ideas from that theory that I got is that the accumulation of damage in our DNA is one of the biggest causes of why we age, which is quite intuitive for a non-biology major like me. Furthermore, there has been research on DNA damage repair pathways and ways on how nanotech can help repair DNA. The technicalities are beyond me. My question is

If accurate DNA repair is such a difficult mechanism to sustain over a lifespan, then why not catabolize DNA and replace it with a new one?

It seems very feasible to synthesize human DNA (please inform my ignorance, if I'm wrong. lol.) and it looks very promising after reading this: https://www.wired.com/story/live-forever-synthetic-human-genome/.

EDIT: It was pointed out to me in the comments that my question is too broad, please do tell me how to make it more specific, if you agree that's the case here. I'm very happy to accept technical answers, since I can always retrace it to the basics.

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  • $\begingroup$ By "we" do you mean nature or medical intervention? $\endgroup$ – Jam Jun 14 '19 at 9:56
  • $\begingroup$ "we" age due to nature...? $\endgroup$ – TheLast Cipher Jun 14 '19 at 14:18
  • $\begingroup$ @TheLast_Cipher Excuse me, I meant when you said "why not catabolize DNA and replace it". My point is, are you asking why we've not evolved to replace our DNA or whether we could use DNA replacement as a medical therapy. $\endgroup$ – Jam Jun 14 '19 at 14:40
  • $\begingroup$ @Jam: I am asking why we have not use DNA replacement as a medical therapy. $\endgroup$ – TheLast Cipher Jun 14 '19 at 15:18
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It seems very feasible to synthesize human DNA (please inform my ignorance, if I'm wrong. lol.) and it looks very promising after reading this: https://www.wired.com/story/live-forever-synthetic-human-genome/.

It is certainly possible to synthesize human DNA, but it's another thing to create a functional chromosome. In fact, in the article you link to, they are discussing a research effort to synthesize a human Y chromosome. As far as I can tell they haven't actually done this yet, they are just proposing to attempt it. George Church is a highly regarded genomicist, but the article is very sloppy about distinguishing what they think they can do from what they've actually done. There has been work with human artificial chromosomes (HAC), but these have been special purpose constructs that successfully replicate and divide in cells, but don't duplicate an entire natural chromosome.

Synthesizing a human genome would just be the start of the therapeutic process. You then face the question of how to place the synthesized genome in the cells of the recipient. Current approaches to gene therapy involve inserting a single "repaired" gene into a virus, and then infecting the relevant tissue with that virus. This doesn't insert the gene into all cells of the body, just the ones infected with the virus. For some simple genetic diseases this is enough to relieve the symptoms of disease. You can't insert an entire human genome into a virus though.

It's also been proposed to harvest stem cells from the recipient, modify them with the repaired gene, and re-insert them in the diseased tissue. Again this would affect only a portion of a single tissue, not all the cells of the body. It's also one thing to insert a short sequence into a stem cell, but nobody knows if you could swap out a stem cell's entire genome and still maintain it as a stem cell. Also, this would only work for tissues that are still actively dividing. Many important tissues (in the brain for example) have stopped dividing or divide only slowly in adults.

Even gene therapy involving single genes has been approved in only a handful of diseases. It's sill almost entirely experimental. What you are suggesting is still in the realm of wild speculation. Speculation can be inspiring and motivates research programs, but don't starting counting chickens yet.

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  • $\begingroup$ Is it correct to say that a DNA becomes a functional chromosome only when it is in an environment where it can be transcribed and replicated? So delivery methods are just as important? $\endgroup$ – TheLast Cipher Jun 10 '19 at 2:58
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    $\begingroup$ @TheLastCipher it's even more complicated than that. Our chromosomes are complex structures with the DNA wrapped around a trellis-work of histones and other proteins. The 3-d structure of the chromosomes plays an important role in the regulation of gene expression and is controlled in turn by a hundreds of proteins coded in the DNA. $\endgroup$ – Charles E. Grant Jun 10 '19 at 3:23
  • $\begingroup$ I would like to encourage further discussion so I'll retract the acceptance of your answer. Hope you don't mind. $\endgroup$ – TheLast Cipher Jun 10 '19 at 15:19
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    $\begingroup$ @TheLastCipher you're welcome to retract the acceptance of the answer and vote it up or down as you see fit. However do note that StackExchanges is intended to be a question and answer site, not a discussion forum, ala Reddit or many others. If you would like an open ended discussion on a topic you can open a chat room once you have enough points. $\endgroup$ – Charles E. Grant Jun 10 '19 at 17:08

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