The jury's still out on Aubrey de Grey's anti-aging claims

Aubrey de Grey's claims that aging can be defeated, which he voiced at TEDGLOBAL last year and at TED2006, "exist in a kind of antechamber of science, where they wait (possibly in vain) for independent verification". While they "don't compel the assent of many knowledgeable scientists", they're also "not demonstrably wrong".

That's the overall (in)conclusion of the challenge put forth last year by the MIT Technology Review to scientists to disprove de Grey's "Strategies for Engineered Negligible Senescence" (SENS). Three submissions by scientists and groups of scientists have been analyzed by five judges - all the details in this previous post - and the magazine announced yesterday the results of the jury's work: "SENS is a collection of hypotheses that ... cannot rise to the level of being scientifically verified. However, by the same token, the ideas of SENS have not been conclusively disproved". The challenge remains open.

(Cross-posted on LunchOverIP)

Comments

[Gregorio]

De Grey's ideas are in fact demonstrably wrong. His belief that metabolism is inversely proportional to lifespan, the rate of living school, is troubled with persistent exceptions and paradoxes - that birds with high metabolism live 10 to 15 times longer than rats of similar mass, that people who exercise (and so raise their metabolic rates) live longer healthier lives when, if De Grey is correct, they should die sooner. De Grey's attribution of the cause of the mutations of mitochondrial DNA being superoxides like hydrogen peroxide, betray an astoundingingly inadequate understanding of electrochemistry, where the production of hydrogen peroxide is something that occurs at the anode of a battery whose poles are immersed in water, while the oxidation that he says is so damaging to the mitochondrial membrane, is to be found at the cathode, not the anode. While the decomposition of that hydrogen peroxide might result in an oxygen atom that could feasibly cause an oxidative reaction, that molecule is bound up, once again, in the form of hydrogen peroxide (a process that involves the reduction of oxygen) by continued metabolism. So metabolism actually prevents the formation of free radicals by binding them up as hydrogen peroxide, and experimental results reveal that young bats have more hydrogen peroxide in their tissues than old bats.

De Grey's rate of living school is even contradicted by the mathematics of allometric scaling which clearly show that higher metabolic rates lead to longer lives. This mathematics eliminates the exceptions and paradoxes that trouble the 'rate of living school', and accounts for the life-extending effects of Caloric Restriction too. The mathematics do not limit themselves to aerobic respiratory considerations alone, but include the oxidative capture of energy by the multi-cellular organism through the digestion of food, and the distribution of that energy to the cells of the organism through the action of the nervous system, where it triggers the formation of hydrogen peroxide in the organism's somatic structures. When that hydrogen peroxide decomposes the charge given off is picked up by the enzymes that subsequently use it to synthesize ATP. The metabolic production of ATP actually reduces the cell's and the mitochondrion's load of oxides, rather than increases them. This is why the math shows that metabolic rate and life span are directly, not inversely related.

De Grey is a flash in the pan, but his showmanship and eccentric appearance guarantees that the flash will continue to redound to the benefit of the rate of living school (which so far has absolutely nothing but empty promises about affecting aging and cannot explain the effects on longevity of caloric restriction) and to the benefit of the preposterous idea that metabolism, necessary for life, is what limits that life by eventually destroying it through the accumulation of damage caused by free radicals like hydrogen peroxide which, it turns out, do not cause oxidation at all. As long as people take this guy seriously they will never see any progress in attempts to slow, stop, and reverse the degeneration of aging.

[aubrey]

Gregorio's comment has just been brought to my attention. Sadly, Gregorio appears as unwilling as most of my other detractors to take the trouble to grasp even the most basic aspects of my proposals before dismissing them. I am perfectly aware of the limitations of the "rate of living" correlation highlighted by Gregorio, as is amply evident from many of my publications. SENS says nothing whatever about that; it does not correlate aging with metabolic rate at all, but with the rate of accumulation of the side-effects of metabolism. (For the avoidance of doubt, I use "metabolism" in the proper sense of "all the processes that maintain our live" and not in the narrow sense "oxygen consumption" that is meant by the term "metabolic rate".)

[Elroch]

Seems to me that Gregorio himself has made some statements that demand a response. Superoxide is of course a highly significant free radical that can result in DNA damage. Superoxide dismutase is a way cells deal with this. Mice with superoxide dismutase genes knocked out live for a paltry 21 days.

More interesting to discuss is Gregorios offbeat view about metabolic rate and life expectancy. As I understand it, the mainstream view (to which I subscribe) is that there is a correlation between the reciprocal of specific metabolic rate and maximum lifespan of species [See PMID 17030408].

Birds are a truly fascinating class of animals, having been highly developed and sophisticated for a very long time (the descendants of dinosaurs, with very high probability). Birds are extreme outliers with respect to the relationship between life span and metabolic rate, and the reason is clear: they have possibly the most highly developed anti-aging genes of all creatures.

One key example appears to be the genes that ensure that birds have exceptionally high levels of a highly potent variant of the important dipeptide carnosine. This is known in mammals to be both an antioxidant (able to prevent cataracts for example) and an antiglycation agent. The prevention of the formation of sugar-protein bonds is probably key to the great longevity of some species of birds.

Gregorio is also misleading about exercise, a topic which I have researched extensively and have considerable practical experience. Exercise has effects which make serious diseases less likely. If one exercised hard 16 hours a day, Gregorio might be correct, but somewhat more common is to exercise hard for a few hours a week. Key effects of this are lower blood sugar, lower blood total cholesterol, higher blood HDL cholesterol, greater insulin sensitivity, more efficient mitochondria, more mitochondria, more glutathione peroxidase. The latter may be key to some of the fundamentally anti-aging effects of exercise.

I can't help but feel that the opposition of some long-serving biologists to the mere idea that the processes of aging should be attacked by the medical research community with the vigour that heart disease and cancer are being attacked is based more on psychological reasons of resentment at radical views from someone who has not been fully initiated into the clique. As a mathematician (ex-Cambridge wrangler), with all due humility I wish that people including scientists took more care with making broad statements that ignore the difference between a correlation and a monotone relationship, and fail to see that intermittent short term increases in oxidative stress do not preclude a long term reduction in oxidative stress through adaptation. Such logical errors are widespread - I am pained every time someone says global warming is not caused by humans since temperatures have always varied naturally, missing the key point that a statistic can have more than one input affecting it. [cf (metabolic rate + antioxidant mechanisms + many other things) affect mean life span]

I largely agree with de Grey's philosophy, and excellent arguments as to why it is not wrong to even consider the possibility of defeating aging. While my gut feeling is that many of the parts of the SENS plan may be more difficult that he thinks (science always is), and that the plan will probably need broadening as greater understanding is reached, I believe the mission he evangelises is a great and noble ideal which is as valid for humans to aspire to as setting foot on the moon.

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[jmackj2000]

I do agree with Grey's theory. Need more research to make it happen.

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