Leonard Guarente’s Anti-Aging Pill (2016)

> The theory behind Basis is in part an evolution of the theory behind drinking red wine: One of its main ingredients, pterostilbene, is considered a more powerful version of resveratrol, with a more convincing track record in the lab. As for NR, by increasing NAD levels in our cells, it in turn appears to reverse mitochondrial decay. In a 2013 scientific paper, Sinclair announced that a single week of injections of an NAD precursor into elderly mice had made their muscles look young again, though without restoring their strength. Both compounds aim to activate sirtuins, and the hope is that together they might amplify what each does individually.

I'll pass.

The greater fool of interest here is the one indirectly funding the ongoing construction of a grand catalog of human metabolism, an exhaustive accounting of the fine details of how our cellular biochemistry operates and ages. This is understood in outline, but beneath that outline lies an enormous unexplored space of protein interactions, causes and consequences, and the relationship of various states in the system to health at every level. The greater fool is told by various parties that the goal is to enhance healthy longevity, but that isn't really happening via these explorations of metabolism, and in truth doesn't have much of a hope of happening via this research strategy. Look at the past fifteen years of sirtuin research in connection with the calorie restriction response, wherein the greater fool was - collectively - the GlaxoSmithKline shareholder community following the Sirtris acquisition. Well-managed hype sputtered out quite quickly after that liquidity event into nothing more than a slightly greater understanding of a few very narrow areas of mammalian biochemistry. This process happens over and again for each new potential calorie restriction mimetic, or other methodology claimed to slow the progress of aging by altering the operation of metabolism. Yet there is always a greater fool willing to buy.

Even if a drug was developed to completely mimic the beneficial effects of calorie restriction, so what? That is a convenience device, no more. Those practicing calorie restriction have somewhat better health and somewhat less age-related disease, and might live as many as five years longer. It's a larger effect than any currently available medical technology can provide. Nonetheless, the large majority of those people do not and will not live to see 90 years of age in the environment of today's medical technology. They still live the last years of their lives in frailty and pain. Why spend billions on striving to create a convenience device to recreate some of this marginal effect, tiny in the grand scheme of things? Because some people can get rich doing it.

The recent history of medical development related to slowing aging is that some folk have found they can do very well thank you by promising the prospect of enhanced longevity, while delivering nothing of value beyond scientific knowledge. In different circumstances I might be inclined to praise this as a great hack on investment community culture: direct more funding into life science research rather than cat pictures on the internet, and take a deserved cut as the individual who manages to make that happen. There are certainly far worse things for the greater fool to be talked into doing with his or her money.

Today, however, this business of making hay while the sun shines, based on ways to slightly slow aging largely emerged from calorie restriction research, is a distraction from the prospect of real progress. Messing with metabolism in this way cannot even in principle produce meaningful rejuvenation: aging is damage, and slowing down the damage does nothing for people who are already old and damaged. Yet there are other research strategies that can achieve this goal: the better approach is to repair the damage that causes aging, following the existing detailed research plans that aim to produce new rejuvenation biotechnologies. These can in principle restore youthful function for the old, extend healthy life indefinitely, and should not be any more expensive to explore and develop than a continued future of whatever the next replacement for sirtuin research might be. If billions are spent, then let it be in the pursuit of technologies that do offer the possibility for everyone to live to 90, and in good health, lacking frailty, pain, and disease.

It's a fight to make this case. It shouldn't be, but it is. Attention continues to be soaked up by marginal, ultimately pointless efforts such as the one noted here. It won't let you live to be 90 in confidence, it won't create rejuvenation in the old, and no foreseeable evolution of this strategy can in fact provide those benefits. It is just more of the same search for the greater fool to retroactively bankroll the continuing mapping of metabolism.

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You might recall the hype surrounding sirtuins in cellular metabolism, followed by the breathless marketing of compounds supposed to affect their expression such as resveratrol, all of which went to the usual destination for such things, which is to say nowhere. Some knowledge was added to the grand map of mammalian biochemistry, some people were fleeced, some people made a bunch of money on the backs of promises that never materialized, and that was that. This happens over and again. Every time a new link is uncovered in the complex chain of protein machinery relating to cellular repair mechanisms, upregulated in many of the ways to extend life in lower animals, or calorie restriction, a practice that extends life in short-lived mammals such as mice, and along the way alters near every aspect of the operation of metabolism, then the marketing begins for any supplement that can be linked, tenuously or otherwise, to that research.

If you recognize the general pattern, then you should be well placed to see how things will play out for nicotinamide riboside. This is yet another molecule that can be used as a supplement, and which influences some of the mitochondrial biochemistry associated with cellular maintenance processes. In mice it has been shown to modestly reduce some forms of age-related decline, either by spurring greater maintenance or greater stem cell activity. It is an open question as how much of this will be recapitulated in humans; short-lived species are much more readily influenced by this sort of thing. Their life spans are plastic, and so are their metabolic operations. Regardless, it is of course the case that a bunch of people got together to form a company in order to sell nicotinamide riboside as a supplement. That company is called Elysium Health.

The differences between this and past efforts of this nature are that (a) more reputable scientists from the aging research field are involved, more is the pity for their reputations, and (b) the whole affair is just a little closer to a sensible take on how to make progress in the field, rather than being an absolute money grab. In fact I agree with a fair bit of what cofounder Leonard Guarente has said in public on his motivations for doing this: that progress must be made more rapidly, that there is a space between the worthless supplement market and the highly regulated world of medicine in which good work can be done, and that it is important to put new approaches out there in the world to gather data. I just don't think that this particular approach has any merit in and of itself. Regular readers will know my position on tinkering with metabolism via drugs and found compounds in order to gain tiny and dubious benefits. It is a a waste of time and effort, and definitely not the road to meaningful outcomes in the treatment of aging. Further, even putting that to one side, the founders of Elysium haven't gone about this in the right way at all. They should have sold their product as an open trial of nicotinamide riboside wherein people pay for participation, doubled the price of the supplement, and used that extra money to collect data from participants. Instead they, as everyone is, are corrupted by the fiduciary duty that comes with running a company where the primary focus is selling a branded supplement - so now they are in the supplement business, not the science business. It should be an object lesson for the next group who are thinking of doing something like this.