How many years of age reversal can we achieve?

NickOttens

If we challenge teams competing in this prize to reduce the biological age of a large cohorts of individuals in a one-year, well-regulated clinical trial environment, what is the best age reduction we can expect to see (as measured by an epigenetic clock, or combination of epigenetic clocks)?

NickOttens

Dear @dalminana, @Ramsey, @abarsouk, @joannabensz, @TheresaB, @ddotdan, we are in the process of designing an XPRIZE competition for age reversal, which is a direct outcome of the Future of Longevity Impact Roadmap to which you contributed here in the community last year.

One of our first questions for the prize design is how many years of age reversal we can realistically achieve? Please vote in our poll to let us know what you think!

NickOttens

Thanks to everybody who has voted so far!

@sramek, @Life, @toga, @TorenM, @jtower, @jtullet and @AngelaT, I'd like to ask your opinion as well: How many years of age reversal do you think can be realistically achieved in a one-year XPRIZE competition if it were held, say, next year?

Our initial thought was to challenge teams to reduce people's age by 5 to 10 years. We want to know if that would be too audacious, not audacious enough, or about right for XPRIZE.

So far, the consensus seems to be that we should aim higher, with 7 out of 10 community members proposing 10+ years.

What do you think?

danbelsky

No age reduction - but no aging either

We asked this question using data from the only randomized trial of a geroprotective intervention to date, CALERIE. That trial randomized participants to 2 years of 25% caloric restriction or ad libitum control. (In mice and other animals, this intervention can extend healthy lifespan.) We found the trial slowed the rate of aging to near zero in the treatment arm. We are now generating a genomic database for the trial to test effects on cellular-level measures of aging. You can find our earlier paper on blood-chemistry measures of biological aging here: https://academic.oup.com/biomedgerontology/article/73/1/4/3834057

Roey

4-6 years

danbelsky wrote: »

We asked this question using data from the only randomized trial of a geroprotective intervention to date, CALERIE. That trial randomized participants to 2 years of 25% caloric restriction or ad libitum control. (In mice and other animals, this intervention can extend healthy lifespan.) We found the trial slowed the rate of aging to near zero in the treatment arm. We are now generating a genomic database for the trial to test effects on cellular-level measures of aging. You can find our earlier paper on blood-chemistry measures of biological aging here: https://academic.oup.com/biomedgerontology/article/73/1/4/3834057

@danbelsky - that sounds promising! Thank you for the link. I'll look into it.

nicolas_cher

15+ years

At the same time that the goal should be feasible, it should be capable to be clearly noticed. If it isn't clearly noticed, it won't have necessarily a big public impact. Here, we are talking about rejuvenation, and for the public, it doesn't mean some kind of obscure genetic test; it means look at somebody (and at what somebody do) and say "you are definitely younger than before". And how to measure that? I just thought of an example: take a former football (soccer) player, like, let's say, David Beckham, the English guy. If he is 50 years old, he simply can't play a professional game in the English football league. However, with 35 years old, he can do it. So, a great way to measure the rejuvenation could be taking a group of former football (the most popular sport in the world) players who are 50 years old (obviously "out of the game"), applying the rejuvenation therapies, and putting them to play a professional level football game against a team of the English league, or other important football league. IF SOME BUNCH OF GUYS 50 YEARS OLD ARE ABLE TO PLAY COMPETITIVELY AGAINST A PROFESSIONAL TEAM OF THE ENGLISH OR OTHER IMPORTANT LEAGUE, EVERYBODY WILL KNOW THEY REJUVENATED, WITHOUT ANY OTHER TEST. AND THE WORLD WILL CHANGE!

Roey

4-6 years

nicolas_cher wrote: »

At the same time that the goal should be feasible, it should be capable to be clearly noticed. If it isn't clearly noticed, it won't have necessarily a big public impact. Here, we are talking about rejuvenation, and for the public, it doesn't mean some kind of obscure genetic test; it means look at somebody (and at what somebody do) and say "you are definitely younger than before". And how to measure that? I just thought of an example: take a former football (soccer) player, like, let's say, David Beckham, the English guy. If he is 50 years old, he simply can't play a professional game in the English football league. However, with 35 years old, he can do it. So, a great way to measure the rejuvenation could be taking a group of former football (the most popular sport in the world) players who are 50 years old (obviously "out of the game"), applying the rejuvenation therapies, and putting them to play a professional level football game against a team of the English league, or other important football league. IF SOME BUNCH OF GUYS 50 YEARS OLD ARE ABLE TO PLAY COMPETITIVELY AGAINST A PROFESSIONAL TEAM OF THE ENGLISH OR OTHER IMPORTANT LEAGUE, EVERYBODY WILL KNOW THEY REJUVENATED, WITHOUT ANY OTHER TEST. AND THE WORLD WILL CHANGE!

@nicolas_cher - I like the spirit of the idea! While I don't think it would be wise to pit 50 years old against 25 years old players, even after rejuvenating treatments, I agree we need some kind of visceral, highly-visible proof that the treatment is working.
Personally, I remember the anecdotes from a recent rejuvenation study, where the participants said they saw their hair darkening again, and had their libido return. I think if we can get enough testimonials like that, people from all over the world will flock to get those treatments

nicolas_cher

15+ years

@Roey - Taking your idea further, we could think about a way to measure the rejuvenation in the following way: the therapies could be applied to, let's say, 200 people, in a double-blind study, with placebo control, etc. and all the scientific standards. HOWEVER, what could be specially measured (together with other kind of tests, of course) is the subjective impression of the people about how young or old they are. In this way, it could be possible to conciliate the scientific side with the general and broad perspective that each person have about their own aging state. Of course, other tests could be done, like epigenetic click test, and many other markers could be assessed, but it would be vital that many people (hundreds) be submitted to the therapies and the study, with placebo control.

Roey

4-6 years

nicolas_cher wrote: »

@Roey - Taking your idea further, we could think about a way to measure the rejuvenation in the following way: the therapies could be applied to, let's say, 200 people, in a double-blind study, with placebo control, etc. and all the scientific standards. HOWEVER, what could be specially measured (together with other kind of tests, of course) is the subjective impression of the people about how young or old they are. In this way, it could be possible to conciliate the scientific side with the general and broad perspective that each person have about their own aging state. Of course, other tests could be done, like epigenetic click test, and many other markers could be assessed, but it would be vital that many people (hundreds) be submitted to the therapies and the study, with placebo control.

@nicolas_cher - that could be a very interesting test, but it should probably be more objective (i.e. performed via a computerized analysis of skin tone, hair density, etc.).

NickOttens

@YuriDeigin, @jinzhouying, @ArthurDR and @MSK, how many years of biological age reversal do you think we can realistically achieve in an XPRIZE competition, assuming it's organized in the next year or two?

Please let us know by voting in our poll!

pscheck

10-15 years

Interesting discussion here. I hope I am not reiterating a point here that has already been made. I think there are two main factors to consider for the competition. If the effect is too small, you may not be able to detect it at all in any sort of affordable trial in one year because the number of humans necessary to is too big. If the effect needs to be big, it may take a very long time to find something that has such a big effect. So the first key question is: where is the sweet spot between these two requirements? That should be roughly determined by power calculations. How big does a cohort have to be to detect a stop or a reversal of 5 years, 10 years etc? Then the question arises on how much such a trial costs? . So if trial costs are in the millions per trial, only very few groups will be able to compete. If the trials can be done for ~250-500k (which is a very low cost for a trial), many more groups will be able to compete. The more people compete the better the outcome. So the first question should be: Is it possible to come up with a robust, low cost, and effective trial protocol that is accepted by the committee as a read out that will enable many groups to participate in the contest.

techspeaker

15+ years

I would opt for the largest amount of age reduction possible but I do have significant concerns about how this would be objectively measured such that the reduction would be obvious to impartial observers. Yes, having older professional athletes being able to compete with younger professional athletes would be obvious, but you would be dealing with a highly selected population. Instead I would opt for a characteristic (or a number of characteristics) that would be highly visible. As was mentioned, a 75-year old with white hair which suddenly darkened and became thicker would be much more noticeable that a 50-year old soccer player who might be able to run faster but might not actually look much different. In addition, this prize is for age reversal, so a 75-year old who simply stops aging rather than gets visibly and physically younger (however that might be measured) might not be the best goal. If it were me at age 75 I would much prefer to look and feel like I was 40 years old again rather then to perpetually stay at 75.

sureshj

15+ years

15+ years

As some of you might be aware, previous studies in C. elegans and Drosophila suggest that it might be feasible to double or triple the lifespan of short-lived invertebrates. In spirt of these studies, I think it is feasible to extend 15+ years of lifespan. I am aware that it is difficult to translate these studies to humans to double the human life span. Perhaps around 15 years might be feasible.

sureshj

15+ years

https://www.nature.com/articles/366461a0

NickOttens

Thank you all for voting and sharing your insights!

@techspeaker, you raise a good point. It's one we've begun discussing internally, and I expect we'll have some discussions for the community on it soon: In order of this prize to catch the public's imagination, we probably want to not just reverse biological aging by a few years but produce visible age reversal in people. Could be hair growing back, people becoming more athletic, improved libido, etc.