I was wondering, SENS seems to be based upon the assumption that there is no active genetic mechanism for aging, meaing there is no simple clock-gene that governs how much an organism will live. In order for SENS to work, aging must be regarded as accumulation of random damage over time.
If this is correct, is there any reason to believe things won't be the same for our most basic organism that we use for a model of eukaryotic aging - the yeast ?.
If de Grey's model for combating aging is correct, shouldn't we expect for it to work for yeast ?.
Let's see, from the seven categories:
1. Cell loss.
2. Nuclear Mutations.
3. Mitochondria Mutations.
4. Death-resistant cells.
5. Extracellular crosslinks.
6. Extracellular junk.
7. Intracellular junk.
For yeast aging, categories #1,4,5,6 are not relevant (yeast is a single cell organism).
So, we are left with:
1. Nuclear Mutations
2. Mitochondria Mutations
3. Intracellular junk
But on a second thought, according to de Grey, Nuclear mutations aren't relevant as well, because our main concern from this regard is cancer, which isn't relevant for yeast.
So, we are left with:
1. Mitochondria Mutations.
2. Intracellular junk.
Could this be it ?.
So, according to my interpretation of de Grey's vision, all we have to do is move the mitochondrial genes into the nuclear DNA of the yeast (assuming we know who they are, and assuming that like in mammals, each protein whose gene is in the mitochondria's genom, is part of a complex which has other participants which are encoded in the nuclear DNA) and find the right enzymes to brake the specific intracellular yeast junk ?.
Is it really all it takes ?. You do realise that people in the lab are trying countless amounts of mutations (for several years now) in order to prolong yeast life, and our best success as of yet, was an increase of 60% in yeast life span (replicative life span, regarding chronological I think the maximum was 30%).
I think that if SENS was to prove itself in yeast, which should be much, much easier than in mouse, or even drosophila, it might not win the hearts of the general public, but it will certainly win the hearts of many scientists. (I am in no way saying it should replace proof in concept in mouse, but if we can make proof of concept in yeast, within 2-3 years, it might be a much smaller pill to swallow that we can ever make it for mouse, it might give a much needed in-between step).
Also, I don't think that using yeast as first proof of concept is such a deviation from the mouse. Afterall, we will have develop protocols for moving those mitochondrial genes in the mouse too, and first doing it for the single celled yeast might prove like a smarter strategy. Regarding the inclusion of intracellular junk braking enzymes, again, first dealing with yeast might make it easier to see what are the basic problems of doing such a thing, before we jump for the extremely complex mouse, with its trillion cells and immune system...
Not to mention that even if someone had the money, and wanted to start proving SENS in mice (or drosophila, or any other multicellular eukaryotic animal) already today, he really can't. We still don't have the needed quality vectors for gene therapy, nor enough knowledge about how to work with stem cells. We still have to wait several years. But, we do have all the technology necessary to try it for yeast already today. In 5 years when the necessary technology will make it possible to start with mice, we won't start from zero, but we'll be able to use much of the information from the yeast (not to mention it will be much easier to raise capital after you already done proof of concept for some eukaryotic organism).
EDIT:
I do realize that the above scheme is only "a first generation therapy" for the yeast. We haven't dealt with Nuclear mutations, which will probably be the next problem the yeast will meet.
Saying that, I'm not sure DNA repair will be such a bottleneck afterall. Today the longer lived yeast strains devide for ~30 times before they die. I don't think anyone is claiming that after 30 divisions they die from DNA mutations. Nuclear DNA mutations might still allow the SENS treated yeast to live for 120 divisions (if not much more), which will be great proof of concept that SENS practically works for a eukaryotic organism.
I think that if you'll ask S.Jay Olshansky, or other SENS opposers (most of the scientific community), they will tell you that SENS will definitely not dramatically prolong yeast life in the near future.
Edited by noam, 02 January 2006 - 07:41 PM.