Fight Aging!

As noted this morning, Juvenescence is the new venture fund slash business development company created by investor Jim Mellon and allies as a part of his interest in the development of real, working anti-aging medicine. No-one is getting any younger, and that includes people with the resources to do something about this state of affairs, should they finally wake up to the ongoing revolution in biotechnology and put their shoulders to the wheel. This is the latest instance of a well-heeled group setting forth in earnest to achieve something in aging research and related biotechnology relevant to treating aging as a medical condition. Is it the most promising to date? Perhaps.

Past examples have included Larry Ellison's initiative, Paul Glenn's support of research, Peter Thiel's support of SENS, and Google's California Life Company, among others. In many cases, the rhetoric at the outset gave some hope that these large investments would be more visionary than a funding of the same old dead-end work on pharmaceutical alteration of metabolism to slightly slow aging that has characterized the mainstream for the past fifteen years. But in only one case was there in fact material support for the better, game-changing alternative, rejuvenation research of the sort exemplified by the SENS programs, the only plausible way to greatly extend lives and turn back aging in our lifetimes. If there is caution and a wait and see attitude related to Juvenescence and the rhetoric from its founders, it is because Lucy has snatched away the ball one too many times these past years. Still, this is promising rhetoric, I have to admit that much. It comes from a fellow who has raised talking up his position to something of an art form, so I'm sure we'll be hearing more of it:

Mellon on the Markets: New "highs" for early investors

On the subject of Juvenescence, I am off to San Francisco with my old best friend Anthony Baillieu to meet my new best friend Aubrey de Grey (Google him!) and my dear colleague Greg Bailey. We are all spending the day at the Buck Institute of Aging - not to be rejuvenated ourselves, but to understand more of the amazing science that is coming out of this institution.

One of the key senolytic drugs in development, being trialled by Unity Biotechnology, first emerged at the Buck. In a nutshell, senolytics are among the first of several compounds that will add significantly to human lifespan in the next ten or twenty years. While more fully described in the new book, these are drugs that clear so-called senescent cells from tissues. Senescent cells become more prevalent as we age, and are cells that are neither dead nor healthy, but which exist in a limbo like state. They contribute significantly to inflammatory disease and their removal, at least in part, is demonstrably life extending in animal models.

We are also visiting another company involved in senolytics, and will be looking to make an investment in it for our venture, Juvenescence Limited, which is jointly owned by Greg, Dec Doogan (formerly head of drug development at Pfizer, the world's biggest drug company) and myself. We have collectively recently invested a largish sum in a venture called Insilico Medicine, which uses deep neuronal networks (aka AI) to enhance medical discoveries, and we have capitalised a joint venture with Insilico called Juvenescence AI which will look to discover five new chemical entities a year for several years, using AI. These are exciting times in the field of longevity, and believe me, staying healthy today will allow you to cross a bridge to ultra-long life in the not too distant future.

Alex Zhavoronkov at Insilico Medicine will, I'm sure, forgive me when I say that I haven't been following the Juvenescence work all that closely because the early focus appeared to be fairly standard aging-related drug discovery in areas that I think have little potential. He knows my views on these matters. Should the staff at Insilico Medicine set their sights on senolytics and small molecule glucosepane breakers, I will be the first to laud their efforts, as that is a portion of the SENS rejuvenation research agenda wherein standard issue drug discovery processes, rational drug design, and improvements thereof can shine. But building more marginal geroprotectors that target mTOR or regulators of mitochondrial function or autophagy or other line items associated with the scores of ways to modestly slow aging in mice? Not so promising. We're twenty years in to that sort of work, and what do we have to show for it? More knowledge of the operation of metabolism, yes, but also a distinct absence of ways to add healthy years to life that are any more effectively than eating less and exercising more.

I think that the evidence to date gives us all good reason to think that there is a low ceiling to the utility of such mainstream work in terms of years of life gained at the end of the day, and that the ceiling isn't going to rise significantly with the input of far greater amounts of funding. It is a fundamental aspect of these mechanisms. Aging is damage, and if research doesn't aim to directly repair or remove that damage, then it will always be of low utility. Try keeping any damaged machine running without actually repairing it. Further, stand back for a moment and take an earnest look at calorie restriction mimetic development versus senolytic development. Fifteen years of the former has given us nothing to compare to the reliability and breadth of effects on aging and age-related diseases in animal studies resulting from a mere five years of earnest development in senolytics. This is because calorie restriction mimetics do not repair any form of damage that causes aging, whereas senolytic therapies to clear senescent cells do. It is that simple.

To return to Juvenescence, their clear interest in senolytics, and all of the obvious incentives to be involved in senolytic development now that the commercial side of the field has been validated by large investments in Unity Biotechnologies, makes me more cautiously optimistic for this initiative than I was when Calico launched. Even if the Juvenescence principals do no more than vocally and materially bolster the senolytics industry, that will still be a great good. Will they in fact do more than that for the development of SENS biotechnologies? We shall have to wait and see.