Aging biomarkers: Which ones are the best?

In this competition we want the competitors to demonstrate that they’ve achieved real and significant age reversal. For that, of course, we need robust, reliable and responsive aging biomarkers.

We’re currently looking at several biomarkers, including DNA methylation epigenetic clocks (GrimAge in particular), the frailty index (even though it doesn’t seem very responsive), peak exercise capacity, TNF-alpha receptor II, CRP, IL-6, GDF-15 / MIC-1, IGF-1, Cystatin C, NT-proBNP, HGBA1c, and telomere length.

Are there other biomarkers you would recommend we use? And are there ‘phenotypic’ biomarkers that you would recommend - things like improved libido, darkening / regrowing hair, smoother skin, and the likes?

Would love to hear what you think!

@efoehr, @Polina_veritas, @AlexZhavoronkov, @amoskalev, @poulain, you may have an opinion on this. Which biomarkers should we use to test if teams competing in this competition are achieving significant age reversal?

Physical attributes can be tested. In our hands, they seem very responsive to interventions.
See this paper we have in press at Nat Commun. It’s simple and reproducible across labs. There’s a website to enter data. http://frailtyclocks.sinclairlab.org/ Preprint is here: https://www.biorxiv.org/content/10.1101/2019.12.20.884452v1
There is also the glycan age from Gordan Lauc’s lab which seems accurate too.

Thank you for sharing, @davidsinclair!

@stuartmaudsley, @gatzmon, @Umbertog, @amoskalev, @Barardo, @SWBT, @dani_chronomics, what is your opinion? Which biomarkers do you think we should use to judge teams competing in an XPRIZE competition to reverse aging?

(More info about this prize design here.)

The above mentioned markers can be useful, but with the caveat that it is hard to distinguish whether they reflect increased health (or aspects of health) or decreased age. These are separable and need to be distinguished to know whether any treatment is simply affecting health or also age. As the field has known for a long time, there are myriad forms of intracellular and extracellular macromolecular damage (literally hundreds of forms) that accumulate over time. They all likely contribute to the frailty of old age. Reliable markers for aging per se would need to measure the levels of biochemical damage, or at least representative sets of damage that occur to proteins, DNA, lipids, and carbohydrates.

Thank you for sharing your insights, @JeanHebert!

@solangemassa, I’m curious what you think about this as well.

I want to add a couple of markers to the list:
Multiple studies suggest that Ig glycans are markers of aging
Extracellular vesicles as markers of aging (particularly brain aging).

Hello, Esteemed Colleagues. This is Rudi Hoffman, new to this list. I am a well-informed layman regarding age reversal, not a scientist or researcher like David Sinclair and some of you. The above biomarkers seem to be a good start. May I ask/observe that in addition to the efficacy of the biomarker test, factors like cost, accessibility, and convenience be considered? I had a telomere length test done, it was about $500 bucks and took several months to get results, and these accurately still showed a broad range of results due to the variability of telomeres, I believe.
And may I say how genuinely thrilled I am about this age-reversal X-Prize initiative, and delighted and humbled I am to be a part of it! I will do my best to pull my weight within the skill-sets I have to contribute.
Rudi Hoffman
Port Orange, FL

Age reversal should imply an extended lifespan to me. If someone claims that a “rejuvenation effect” has been achieved, that should mean making a living organism really younger, right? Would it be too simplistic to just apply a treatment to an animal/organism really old, and close to death to see if instead of dying as it was supposed to do <8in a few months maybe), it continues to live?

In addition to molecular markers it can be worthwhile to consider phenotype markers such as skin aging. As far as I understand skin age can be analyzed with AI to predict age and even potentially detect some diseases; it should also be easy to evaluate as you just need to take photos with consistent lighting – which is a big plus for trials. In my view, skin age wouldn’t make a lot of sense stand-alone (we wouldn’t want simple cosmetic products to count as age reversal treatments), yet it could be a useful extra indicator in a composite marker set.

One company/group that does promising analysis is https://haut.ai/, although perhaps there are others.

Thank you all for sharing your insights and feedback!

@rudihoffman, the issue of cost is definitively one we need to consider. Our researcher are looking into that and I expect we’ll have some questions for the community on that topic in the next few weeks.

Thank you for your response, Nick. My main contribution to this group will be helping recruit people who are much smarter than I in this topic. I have already reached out to some of these, and will continue this effort to increase collaboration and support.
Rudi Hoffman

Thank you so much! Please feel free to share the link to the community with your contacts or connect them with me by email.

Absolutely! The company’s founder, @nastyahaut, is even a community member.

Let me add a separate discussion on automated phenotypic assessments.

@mikeant thanks for bringing this up. An idea for an unbiased method using skin imaging - use body skin or hands. These parts are treated with cosmetics at a lesser extent and can be standardized.
I think biomarkers dynamics and response to intervention can serve as a biomarker itself.

Thank you, @davidsinclair ! The FRIGHT and AFRAID clocks are just what we’re looking for in terms of composite markers, but have only been developed for mice. Would you happen to know if there are similar clocks for human beings?
We’re also exploring the GlycanAge clock for humans at the moment. Thanks again!

True that, @JeanHebert , and thank you for emphasizing the distinction. We’re trying to both measure factors that influence lifespan (more related to biological age) and healthspan (more related to general health).

Thank you, @sureshj . We’re looking into the GlycanAge clock right now, and it does indeed seem promising!

Hi @rudihoffman . Good to have you here. We’re excited and thrilled about this project as well, and truly believe it’ll bring about real change!

@Stefania - that’s only partly accurate, I’m afraid. While we do want to achieve a rejuvenation effect, if the treatment is being applied close to death when too much damage has been accumulated, we can’t expect it to work instant wonders. My guess is that the treatment would reach its best efficacy when given in adulthood or even old age - but before too much damage has been sustained by the body.