To dovetail off what John is saying, Alex, how do you think the biohacker community at large can help move the industry forward faster? Are there things that we do here (or can or could do here) that might help your efforts in the longevity biotech arena? Does the data that people present here and n of 1, cases, provide any value to your type of firm? (in aggregate and as early leading indicators, for example).
1 Like
I recognise there is truth in what you say. I am myself quite surprised at what changes I have been able to make over the past few years. Much that I have a white bushy beard a lot of function changes have occurred.
1 Like
Those changes are too small to be significant. What I’m talking about is something undeniable, like visibly becoming younger over just a few years of treatment.
1 Like
This is a useful discussion.
What changes are you referring to.
Why are they not material?
Like some already healthy 80 year old suddenly having the performance of a healthy 30 year old.
2 Likes
Yes, but this appears to be about me not some random 80 year old.
1 Like
It wasn’t about you, but if I may give honest feedback.
From your pictures, you certainly lost weight and gained some new black hairs. But if your treatment was THE silverbullet for aging, you should look physically younger which you don’t. With dutasteride, minoxidil and tretinoin you would’ve likely recovered far more black hair and gotten rid of some of the wrinkles over a period of 4 years than with your current treatment.
2 Likes
What I enjoy about this forum is the openness to investigate interesting science that is often critically overlooked - just take rapamycin for example 
I’d say the usual discussions regarding sharing papers about interesting drugs, pathways is very helpful!! Nuanced dialogue about early leading indicators is always useful too.
-Alex K
5 Likes
The really interesting approaches are those that promise one-shot, top-down rejuvenation:
-
Michael Levin – He’s done a lot with regrowth of limbs and other amazing bioelectrical phenomena. His work with planaria reveals that their genome is full of garbage but that doesn’t affect them. Bioelectricity is the primary determiner of the physical form of that species. Maybe it would work in humans too, and bioelectricity could be the means of directing the body to rejuvenate.
-
Harold Katcher – E5 rejuvenated old rats by several measures. He speculated that, if it worked in humans, a treatment could last several years then the next could set time back for another several years, and so on. Maybe a combination of E5 and plasma dilution could reduce the volume of E5 needed, thus making it more commercially practical.
-
David Sinclair - He and others have rejuvenated mice, without cancerous side effects, using intermittent application of all four of the Yamanaka factors, or by application of three of them.
-
George Church and Noah Davidsohn – They have used genetic modification to rejuvenate cells, delivering to specific cells via virus and other methods. There is the possibility of finding types of cells that, once rejuvenated, will modify all the rest of the cells in the body.
Those are some categories that occur to me at the moment, but there are bound to be more. Rapamycin, supplements and healthy lifestyles can keep us propped up while we’re waiting for a real one-shot, top-down rejuvenation treatment. Brought to market, no piece-meal interventions could survive in its shadow. Forgive me for stating the obvious.
2 Likes
@invivo the list of efforts/projects by @argonaut above are what have gotten people very excited here. Are you guys invested in any companies working in these areas?
Do you have a feel for the timeline for any of these projects above to actually get to market (if all goes well)?
Also - some other random questions:
-
What is the typical size of your investments? Are you guys only seed and series A focused? From an investment perspective, how much of your focus is SF Bay Area, vs. other areas? Do you see other geographic areas becoming more active in the longevity biotech startup space?
-
What does your company think of mitochondrial transplantation as a general area of rejuvenation? Is that a general area that you guys are bullish on? Or is the science still too early?
-
What companies in the longevity biotech industry, broadly speaking, do you think are likely to introduce products to market in the next few years? From the sounds of things - it seems likely that Loyal is targeting 2026 for their dog IGF-1 lowering product, and BioAge sounds like they may be out in a couple of years with their muscle / sarcopenia drug in a similar timeframe if all goes well. Are there other ones you’ve heard of that look interesting and perhaps available in the next three years?
-
What is the general thinking inside your company about off-shore projects like Minicircle and the Follistatin / plasmid gene therapy? Do you think that off-shore approaches are more likely in the industry, do you think it will speed up delivery of safe and effective longevity products? Or do you guys see it as too risky and potentially a black eye for the industry if something goes horribly wrong and someone gets seriously injured or dies in these types of projects?
-
Are you hearing any rumors about progress or lack thereof (or is it far too early) in Altos labs? How about Calico and ISRIB, or other molecules? Calico seems like a very slow beast and most people I’ve talked to have written them off, but are there other opinions out there I’m not hearing?
-
What is your company’s take on the issue of the FDA and the lack of “Aging” as a condition that they recognize as an endpoint to target. Does your company think that this is, or is not, a factor in slowing the approval of new drugs targeting aging? Or is the current approach of targeting an age-related disorder (e.g. muscle wasting / sarcopenia, cancer, etc.) fine and is a reasonable path to get FDA approval?
-
I know that Alex Colville worked in a family office previously. Does he have any insights into why the projects like TAME (Targeting Aging with Metformin) clinical trial are having such a difficult time getting funding from high net worth individuals interested in aging, or a similar type of project on rapamycin? Is it just that its not likely to have as big an impact on longevity compared to the moonshots that Altos and others are doing? Or is the lack of a financial return a key issue?
-
I know that most of your team is probably under 30 years old, but is anyone on your team doing anything interesting in the way of personal longevity efforts, and willing to share them?
7 Likes
@invivo , I see that your background is partly in data science. Do you (and your people at your company) see opportunities for Biohackers to contribute to speeding the progress in the longevity field?
I’m wondering if there is a missed opportunity right now via Biohackers like the people here, but somehow aggregating better / cleaner data in a controlled fashion so that we can get more data and then work with longevity researchers (academic groups) that can parse out what the real benefits or downsides are of the compounds / drugs that people are taking and using.
I’ve thought about doing a proposal to Hevolution fund for a Biohacker’s Longevity App that allows you to easily track your results (i.e. data from Fitbit/oura/GCM, etc.) , and your interventions (longevity oriented supplements, drugs, therapies like plasmapheresis, etc.).
I’m thinking that over time, with enough people, it might gain some meaningful data. I spoke with Andrea Maier (NUS) at the recent Longevity Summit and she liked the idea and was interested in partnering. But I’m still unsure about it… and I don’t have the time right now, but it seems like a reasonable way to go, given our constrains in this market segment. I’ve done an app like this for a Pharma company looking to validate real-world outcomes on a new drug (Patient reported outcomes are a big thing for the FDA; they want to see a measurable improvement in quality of life for patients, so this type of app was going to be very helpful for them, and I think the same is true broadly across the Pharma industry). We could integrate these forums right into the app, so it would be an app that you interact with frequently.
Do you see much potential value for data like that - or is your impression that the data from biohackers is too dirty, too many compounds being used, too many confounding variables…?
We’ve done polls in the past of people here to get some data, but obviously this is a less than ideal approach to tracking people. Ideally you’d want longitudinal data over a 2 to 5 year period, with the ability to track changes to a given person’s regimen, and outcomes over time.
4 Likes
Honest feedback is best. I could just be an old fool with wishful thinking.
Lets start with the assumption that my hypothesis is correct and that the main problem with aging is that the genome stops functioning properly and hence produces too few of the proteins (particularly more complex ones) that it should. (potentially none).
This gradually causes malfunctions at a macro level. If you fix it, however, it does not mean that suddenly everything will change. What changes is that the cells start functioning more effectively (and that I think is gradual because of the interplay between histone acetylation and DNA methylation).
So where you have cells that are not active nothing changes. When it comes to things like maintaining skin flexibility cells with a bad blood supply (such as on the shin) don’t really change that much. Other cells, however, start rebuilding the extra cellular matrix (as long as there are sufficient materials).
Hence you would not expect a sudden change as if someone is placed into a device which suddenly makes them look 40 years younger.
I am deliberately avoiding cosmetic interventions as I wish to monitor what happens without cosmetic interventions. Obviously if I used the cosmetic interventions they would add to what I have been doing.
I am also more concerned about substance than appearance. Hence the fact as far as I can tell I am not becoming frail, but instead becoming more robust is good. For example I would like to find a way of measuring CRP with a sensitivity below 0.15 mg/L as my CRP is now below that figure.
2 Likes
There is a challenge with using data from a community that is not randomly controlled, yes; no less with the selection bias of folks optimizing for proper health. As you mention, QOL metrics are a nice addition, but not sufficient on their own. Compelling data would involve tracking physiological measures, as well as incidence of chronic disease over a longer period of time. We’re actually writing a post relevant to this right now!
-Alex K
1 Like
- Yup - we mostly invest in founder led seed stage and series A startups, though we do from time to time do following rounds into portfolio companies we support. We certainly do not discriminate by geography - though quite a few of our portfolio companies happen to be in SF as much of our team is based there.
- Can’t speak for my team on this one, but I am personally unfamiliar with the space. Sounds cool though - care to share some links about it?
- You nailed 'em. Hard to definitively say though with us entering terra incognita in getting aging drugs approved. We’re invested in a medical device company called Science, run by ex Neuralink R&D legend Max Hodak - the path to approval tends to be quicker for medical devices. Hopefully not jinxing it!
- We are more bullish on clinical trials being done here in the United States, following rigorous FDA guidelines.
- Don’t think I have much information about this, sorry
- It certainly is! We would love to see a drug approved for an indication of aging. We wrote about this in our piece released last quarter - $200 Billion in Revenue: How an Aging Drug Will Conquer Pharma
- Will get back to you on Alex C’s perspective
The consensus, fwict, is that it’s difficult to raise money for a trial on an already generic drug, which is really unfortunate. Never say never though! - I take taurine! I think one of our team members takes creatine. No medical advice to share though haha
-Alex K
3 Likes
Don’t get me wrong - thinking about theory of aging is fascinating and we talk about it all the time as a team purely for fun. I’m not sure a theory first approach will be a path forward for this field, though. We will very soon be releasing some posts that offer interesting and varied perspectives on emerging science trees to treat age related disease. Stay tuned!!
-Alex K
3 Likes
The idea of mitochondrial transplantation represented by Mitrix Bio - see here: Highlights from the 2023 Longevity Summit
2 Likes
If you are looking for synergistic effects you need to have some idea as to the mechanisms you are trying to influence otherwise you end up with pot luck on combinations as the ITP are finding.
In any event I do a lot of testing and have a lot of positive results. I developed the theoretical analysis based both on papers from others and my own results.
Hi Invivo, I have a bit of a different view on this that I will share with you for what it’s worth.
First, I don’t think we will ever find a single intervention that will do what you suggest. Like looking after a car; if you want it to stay in good nick, there are lots of things that need regularly attending to.
Second is I think if your aim is profit, you are missing your major market in your current plan. Staying young is much more important to women than men.
This is not just vanity. Like it or not, women’s worth in our society is directly linked to us looking young and staying thin.
Women generally will do much more to attain these goals than men. Look at all the clinics that have sprung up where women pay hundreds of dollars to get injections in their lips.
Instead of simply investing in research–which is still great–I would suggest you need to invest in people. Influencers who are not doctors or science geeks - but women who are turning back the clock have an enormous potential audience these days to promote the concept of health span along with tons of products, exercises, treatments etc. that unlike Ozempic, are genuinely good for their health. There is plenty of room for a new Oprah, and what is she worth to her producers?
There are already women doing this but too often it gets bogged down in science (and conflicting science) and gets boring and takes too much time. What you need are women who are genuinely turning back the clock sharing what they are doing without trying too hard to convince people with anything but genuine results. It also need to be produced extremely well so it stays fun.
I wish I had started 3 years ago and I could have documented a ton of stuff on camera that I have done that has taken me from looking like and old women to being mistaken for my 24 year old son’s girlfriend LOL.
What bit of what I did go the results? I will probably never know, But it certainly had to do with exercise and sunshine and not just suppliments and drugs!
2 Likes
14 AMPK activators are rather many. May I ask which one you use and how you rank their importance?
When running AMPK activation using those I take them all and have not got a sequence of importance. A lot are TCM Yang Qi herbs cf ginseng