Aging, Quantified

XPRIZE

Outcome

A set of aging biomarkers that will be accepted by the community of longevity and aging researchers and utilized as a benchmark in any R&D effort in the field.

Why the Need?

There is currently much confusion and disagreement about the best way to quantify biological aging. It is already clear that a single biomarker cannot shed enough light on the aging process, but no one set of aging biomarkers has been accepted by the longevity and aging research community so far. Without a well-established set of aging biomarkers, it is nearly impossible to quantify aging in individuals with precision, and to understand how well a certain treatment works. A set of aging biomarkers would also help in raising public awareness of the issue of aging, as individuals will be able to easily ascertain their own biological ages.

Stipulations for a Successful Breakthrough Solution

The set of biomarkers must fit the criteria established by the AFAR, according to which the biomarker or set of biomarkers –

• “Must predict a person’s physiological, cognitive, and physical function in an age-related way.”
• Must be testable and not harmful to test subjects, as well as technically simple to perform.
• Should work on animals as well as humans.

Finally, the aging biomarkers should be able to reflect a reversal of the aging process.

Promising Technologies for Solutions

While there are some promising aging biomarkers – for example, epigenomics-based Horvath clock – they are still controversial. Additionally, Horvath’s clock does not reflect the effects of age-reversal treatments.

Expected year for proof of concept: 2022
Expected year for mass-scaling: 2028

NickOttens

@efoehr, @AlexZhavoronkov, @Wally, what are your thoughts on this potential breakthrough? Do you think it would be audacious enough for an XPRIZE?

efoehr

I agree that a well defined collection of biomarkers and clinical endpoints is critical to the successful development of therapies to treat diseases of aging. Clinical or physiological markers such as grip strength, walk test, cardiac output, memory test, or of course something like overall mortality are very important. Regulators are unlikely to approve therapies only based on a blood test type biomarker or measurement of DNA methylation pattern. However, it is important to develop and validate these types of biomarkers. Clinical validation of a biomarker requires years of study from multiple researchers and measurement in properly powered and designed clinical trials (i.e. blood glucose, cholesterol, etc). The biochemical marker needs to correlate with the disease state, respond to treatment and be accurate and statistically measured. This is a great challenge and is audacious. But may be too 'diffuse' for a single XPrize since it takes dozens to hundreds of studies over many years for many age related diseases.

Polina_veritas

I think we need a set of biomarkers that showed the effect of a longevity intervention in a reasonable timeframe - an actionable biomarker / a panel of biomarkers of aging. The problem is how long should animals/ humans be on an intervention to see the effect. Animal experiments demonstrated that calorie restriction and 'genetic interventions' have an effect on epigenetic age (for example https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5578459/), but the effect was observed in animals that were on CR for 10 months at least, with 10 months showing the less age reduction and 2 months no effect. The lifespan of a lab mouse is around 3 years, so 10 months is almost one-third of their life. This suggests that epigenetic changes associated with interventions are rather gradual, which complicates the use of those clocks in a clinical setting. I would expect that therapies that have a direct effect on epigenetics would have a more pronounced and fast change in epigenetic age.
At the same time, I can clearly see that clinical trial engagement / increasing the follow-up rate is another key area where biomarkers can help. If we are talking about aging - it something that usually humans can hardly perceive. For a clinical trial, it could be really problematic for patients not to see the immediate feedback from therapy as they won't follow up with a clinic running trials. Having a biomarker that can show patients that they got younger can solve this.
Agreed that is a great challenge, and it is definitely needed by the industry. I am also excited about the potential of those clocks in evaluating and quantifying lifestyle and human behavior.

Natasha

Personalized medicine biomarkers seems to be a smart way to regain emphasis on biomarkers as credible.

LisaCovington

@Polina_veritas any thoughts on what that 'reasonable time frame' might look like?

Polina_veritas

@LisaCovington I would say 0-2 years with the optimum in 3-6 months if we are thinking about the timeframe of clinical trials.
Another point would be how long the effect of the therapy will be observed. It could be the case that biomarker only changed in response to the intervention but after a short period of time, everything goes back to the way it was. I can think of such therapies if the biomarker is also a target of the intervention.

SamBlake

@Natasha are there any efforts making progress in that area that have caught your attention?