Considering Juvenescence

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.


I for one am glad there is serious money entering the field its about bloody time!

Posted by: Steve Hill at August 1st, 2017 6:49 AM

I really like this statement by Jim Mellon: "my new best friend Aubrey de Grey"

Posted by: Nicolai at August 1st, 2017 11:47 AM

All I see here are positives. We have been lamenting the lack of funds and lack of visibility of our community. Now we have a top notch, highly influential group of investors seriously looking at all aspects of life extension. Prior to this, sure we had Ellison, Calico, HLI etc, but this is much broader support. He's clearly working with Aubrey and that can't be a bad thing in any capacity.

Jim is pretty influential in Europe, especially the UK. Private investors really listen to him, and he has a really good track record. I've watched him from the periphery for a few years, but after April's Master Investor show where he gave his big speech, I had to dig deeper. I went and read all his books, and dug up his blog posts and tweets. I was impressed that someone so new to the movement was so well versed in the basics. He's also VERY good at finding management teams. We have several years of his material to look at, we can gauge his accuracy rate. Its pretty high!

Anyway, we've all seen Jim's talk at Master Investor this year, have a look at a couple of the others from our community that came. Lindsay Wu who works with David Sinclair gave what looked to be his first investor pitch (Good for him! I've done a bunch of these and facing the "Dragons" are never easy. You always sing Kum-Ba-yah just before you go out).

Alex gave a great primer on what they are doing, and obviously he hit gold there. THIS IS GOOD. We are getting exposure and funding. More will come. Will it all be allocated in productive endeavors? Nope. That's not the way it works. Its educated hit and miss, and a little luck. We just need some wins to REALLY bring in the money.

Alex Zhavoronkov

I'm also glad that they are keeping In-Silico and Oisin private for now. Boards can pull a companies focus away so quickly. Our community needs to remind investors CONSTANTLY that this is a Marathon, not a sprint. We HAVE to get this one right. Our lives are very much depending on it.

Now since Alex was there and I wasn't... If you are reading this Alex, could you share a few things? I'm not asking for breaking NDA's or anything :), but if you could tell us a couple things about general interest in the participants attending as well as the turnout for the various talks... I'm sure we can glean something from it.

Posted by: Mark Borbely at August 1st, 2017 2:53 PM

To be honest it looks like Juvenescence is going to do more of what has already gone before. A bit of senescent cell removal, trying to get Nicotinamide or whatever David Sinclair reckons will rejuvenate mitochondria, and some other small molecule mess with metabolism bollacks.

If they announced that they were investing in Glucosepane breakers or something else that has not already been well demonstrated then I would fall off my chair.

Posted by: Jim at August 1st, 2017 8:24 PM

I like FightAging and someone I respect routed me to this specific thread suggesting that I should provide an expanded comment.
While this deal is less than 1 hour of the annual NIH funding in monetary value, it is very significant and provides the ability to improve our AI systems, validate them experimentally and try to take some of the molecules into clinical trials. It will also bring more HNWIs to invest in longevity biotechnology, which is the only area everyone should be investing. Aging is very bad for the global economy and productive longevity will be the main source of economic growth in the future.
My team is 100% dedicated to augmenting human performance, but we are trying to do that in the most credible way. Indeed, we do have a large group dedicated to senolytics and the process of SASP formation, interaction with other cell types and the changes in the cell composition in multiple tissues. We use rather sophisticated, but biologically-interpretable AI to track these changes. On our website we show a portfolio of senolytics for over a year, but these molecules need to be administered in combinations and with the tissue-specific delivery and we are still learning how to do that. Humans are not mice, but there is some existing clinical trials data to be analyzed. This is why we have not published.
There are over 150 projects in the company with multiple collaborators worldwide and there are projects in regenerative medicine, gene therapy, aging biomarkers, etc. Most of my team members are hired through competitions, don't have families and work 18-20 hour days with no weekends and holidays considering human augmentation to work harder and doing more outreach to get more people to transition from IT into longevity AI. Previously I funded these efforts using my own funds and I am still unpaid as a CEO. So it is sad to see the very narrowly-focused experts discussing what we should and should not do. The best way to argue is to prove us wrong by demonstrating substantial repair in humans using the alternative methods. The beauty of turning longevity research into a business is that once investors realize that there are substantial profits to be made and solid business cases, they will be pouring money into this sector fuelling more companies like ours and fostering competition. Right now there are billions being poured into projects that make people pay to waste their time and get a distraction from the real problems like aging. So when we see an announcement of funding by someone in the field, it would be wise to promote it and ignite investor interest, because they will be looking for more opportunities. This is how the Computer and the Internet revolutions came to be. Both required enormous investments and returned unprecedented profits.

So stay tuned and just add "Insilico Medicine" into your google news tracking system and track our papers, because we have a policy of publishing the stuff which is 1+ year old.

Posted by: Alex Zhavoronkov at August 5th, 2017 10:27 PM

Thank you so much Alex!

I already have Insilico Medicine on my trackers :)

Good to see you are talking with Big Pharma and with the contacts you are making, I have no doubt you will be making waves for decades to come. Thank you so much for the work you are doing!

Posted by: Mark Borbely at August 22nd, 2017 9:20 PM

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