Ray Kurzweil Expounds on the SENS Rejuvenation Biotechnology of Allotopic Expression
Way back when, Ray Kurzweil put in a good word and modest donation to assist the early growth of the Methuselah Foundation and SENS rejuvenation research. He was one of the first to do so. Since then, however, I really don't recall seeing mention of SENS or specific branches of SENS-like biological repair research from Kurzweil in public media appearances, through you'll certainly find that sort of material in his books. He generally focuses on applied neuroscience, strong AI, mind-machine interfaces, and that sort of thing.
So this article caught my eye, and those of you who are waiting to see what Google's Calico venture will do can add this to your collection of hopeful prognosticator's tea leaves. Here Kurzweil gives a layperson's overview of the SENS approach of allotopic expression of mitochondrial DNA, a way to make the age-related accumulation of damage to mitochondrial DNA irrelevant and thus remove it as as a contributing cause of degenerative aging:
Google's Kurzweil says the machines will think for themselves by 2040, and oh - we'll be immortal
Kurzweil is also involved in one of Google's other side projects, Calico, which is about as far from the company's core search-revenue business model as possible. It's doing medical and genetic research with the goal of ending aging. It's something Kurzweil thinks is possible to do through genetic re-engineering.
The example he gave here is mitochondria, a component of every living cell that metabolizes energy and is critical to life. Mitochondria started out as a kind of bacteria that were captured and consumed by living cells many, many eons ago, Kurzweil said. Consequently, they have their own genome separate from the rest of the body, stored in separate DNA from the cell's nucleus.
Mitochondrial DNA is more prone to errors as the cell replicates itself, which can lead to a host of health problems. Kurzweil said that nature actually addressed this by moving much of the mitochondrial genetic code into the nucleus where it could be stored in less error-prone DNA. But because of the way natural selection works, this process stopped before it moved some bits of the code which only come into use later in life, after a person would have normally reproduced. Kurzweil thinks humans can finish this process and solve some of the deleterious effects of aging.
One would hope that there are also other advocates for aspects of SENS inside Google these days, though so far the known hires to lead Calico are people with far more sympathy for the doomed mainstream approach of drug development after the calorie restriction mimetic model, aiming only to slightly slow aging, and with no hope of significant progress towards longer lives on the timescale that full funding of SENS could provide.
I'm still not convinced moving the rest of mitochondria dna to the nucleus is necessary.
While it was believed there was neuron loss with aging, there was an article suggesting this only occurs in diseased states, aging can occur with negligible neuron loss in measured tissues.
Soon we will have the bowhead whale genome(where some of the most metabolically active cells can last for over two centuries), if it has SENS mitochondria modifications, I'll agree it seems necessary. But if it doesn't, and I think it is likely it doesn't then it will show there's alternate methods to preserve mitochondria quality.
@Darian - While it will be interesting to see how the bowhead whales maintain mitochondrial function for 200 years, it might not be that applicable in humans.
One of the key insights of the SENS approach to anti aging is that it is probably much easier to repair the underlying damage than it is to adjust metabolism to mitigate that damage (or adjust metabolism to slow the rate of damage accumulation down). Because metabolic pathways are interlink and very complex, making a change in one area often has many side effects. Rather than get caught in this mirror maze, getting rid of the damage is easier.
And while there may be some drugs that can mitigate mitochondrial damage to a degree in the short term, they will fail anyway as more damage accumulates. So it is probably better, and easier, and less costly to develop, to just fix the damage periodically.
From what I understand it seems that per neuron metabolic costs remain approximately constant between species. It is likely that functions are highly conserved. We already saw in rodents that double original host species lifespan was possible on neurons. If we boldly hypothesize this finding may apply to humans then human neurons might hypothetically function for over 240 years if transplanted to a species with such lifespan.
My belief is that the mechanisms for preserving mitochondria quality were necessary to attain multidecade function without reduced metabolism in neurons in longer lived species.
Now one of the changes that I've heard seems to occur with age is an increase in membrane peroxidation index for unknown reasons. IT seems likely that even if mechanisms exists that can preserve mitochondria quality, the homeostatic balance can be broken by increasing damage production through things such as changes in membrane structure(which hint at programmed aging, imo), and this may be the factor that results in lowering quality of mitochondria.
It is overwhelmingly likely that whatever mechanism the bowhead whale has that allows it to retain function for 200 years, that it involves merely slowing down the rate of damage, rather than reversing the damage. As such, even if it could be replicated in humans, it wouldn't be all that useful in people who are already old.
Neurons demand a lot of energy, even a few minutes without oxygen and they begin dying. The idea that significant neuron loss with aging occurs was challenged a few years back by a study showing that this is only the case in diseased state, neuron loss is negligible in measured tissues of nondiseased aging brains. Given mitochondria's vital role this suggest that for decades their quality has been maintained in nondiseased states.
The longest living human lasted over 120 years, and it is reasonable to assume that the neurons could've easily outlived the host. As I mentioned previously neurons have shown double the original hosts lifespan on transplant experiments, if this applies to humans. We may already have mechanisms for mitochondria quality that are sufficient for multicentury lifespan if not for indefinite lifespan.
There have been experiments showing that mitophagy mechanisms can selective target the more dysfunctional mitochondria increasing mitochondrial population quality
It may be that mitochondria quality control was necessary to indefinitely maintain the high energy output necessary for neurons, cells which should have lots of highly reactive species given their high metabolism.