Tentative Thoughts on the Cost Effectiveness of the SENS Foundation

WILT, for example, might kill people or animals for years and years whilst the bugs are ironed out because they won't get the cell replacement therapy right.

'Ironing out' is an understatement... how the heck do you get fingernail stem cells into the right spots and replenish every hair follicle? Bone marrow is easy, those cells move through the blood and colonize their proper niches when they flow through the bone. But solid tissue, with immobilized cells and extracellular matrix?

MitoSENS will unearth the complexities of mitochondrial DNA and why it's hard to move it into the nucleus.

Oh hell yes. The animal mitochondrion is a crazy jerry-rigged mess with a genome more overoptimized than many viruses, bizarre specialized ribososomes specifically optimized for making the handful of proteins that the mitochondrial genome codes for while at the same time being obviously slapped together from spare parts, RNA-editing that sometimes is unclear what is important and what is noise, and some of the genes may need to be in the mitochondrion for the purpose of real-time regulation. And the same core set of genes coding for large, hydrophobic, membrane-bound proteins have failed to move into the nuclear genome in all branches of life because that stuff is damn hard to get through two membranes without having it congeal into pellets of inert goo. I've seen interesting work of late involving trying to get RNA-channels embedded in mitochondrial membranes to allow cytosolic RNAs with the proper signal sequences to get into the mitochondrion to be translated there, with some success, but I have little reason to think that such a system would improve upon normal mitochondrial function because poking a complicated system will often just make it worse. This is not to say that mitochondria are perfect, you can imagine in five seconds about twenty ways to make them better than they are - none of which are things you can do by simply going in and making a few simple mods to an existing eukaryotic system.

On another note it is pretty well impossible to get in and modify large fractions of cells in a living organism as opposed to a monolayer of cells in a controlled environment in a laboratory. This being said, I think one of the most fruitful avenues for actual anti-aging research would be looking for ways to chemically boost protein chaperone/recycling activity and improve the regulatory interactions between mitochondria and the cytosol.

SENS could at least change the world eventually and affect billions/trillions of lives, whereas givewell's third world aid is always going to be a tiny drop in a gargantuan ocean.

This seems backwards to me. GiveWell's third-world aid probably has big indirect effects, since it's acting to lift these societies from a bad equilibrium of enduring poverty and underdevelopment. SENS is an interesting research program within gerontology, but that's the kind of thing that's going to be pursued anyway if there's any chance of it being useful. We see this quite directly with RepleniSENS, i.e. stem-cell research, which is a thriving field already - there's no reason why this could not apply to other parts of the SENS project. Sustained economic growth in the third world would be a big boon to all sorts of science anyway, due to increased scale if nothing else.

I wouldn't say pouring money into the developing world is a tiny drop.

Bill Gates 2014 Annual Letter gives evidence that it's a very good investment.

http://annualletter.gatesfoundation.org/

It can't be a few hundred because that would imply that the non-natural-causes death rate is about 20-30% of the natural-causes death rate, which isn't true.

If you have a 0.1% per year chance of dying "non-naturally", the probability of you surviving for 100 years is 0.999^100 = 90% which looks to be order-of-magnitude correct for contemporary Western countries. This implies that your chances to live for 500 years are 0.999^500 = 60%, for a thousand years -- 37%.