Whilst looking through recent papers about biomarkers, this recent open access paper crossed my desk. The paper is the latest in a line of top-to-bottom reviews of aging biomarkers for humans.
With companies like Unity Biotechnology and the David Sinclair lab entering human clinical trials later this year for senescent cell removal and DNA repair respectively, the development of effective biomarkers to measure how someone is aging and how therapies affect it are a matter of urgency.
Looking for quality biomarkers of aging
Given that there are various causes of aging and that rejuvenation therapies will generally only target one or two of these processes, the first therapies will likely only be partially effective. The aging processes are all interlinked as well so affecting one may effect others, hence there is a need for a comprehensive panel of biomarkers in order for researchers to prove the efficacy of therapies.
Another thing to consider with a therapy such as senescent cell removal is, whilst you can measure how effective it is at removing senescent cells (to a reasonable degree using β-galactosidase, etc.), being able to demonstrate the wider benefits of doing so is trickier.
So the challenge here is to find a suitable range of biomarkers that can provide a good level of proof that rejuvenation has occurred when using these therapies. This means various measures of functional age and health are required, and these measures should be something the research community as a whole agree upon as being suitable.
The search for consensus in the academic community
There is no shortage of suggested biomarkers, indeed one only has to look at the myriad of journals on the subject to see there are many to choose from. Metrics ranging from simple functional age measures like grip strength, gait and balance, to more complex measures such as DNA methylation (which measures age based on changes to epigenetic markers in the cell), are all possible candidates for creating a panel of biomarkers.
Unfortunately, the research community has yet to reach consensus on what biomarkers are generally agreed upon. This is due to a number of issues – firstly, the matter of showing that a given biomarker is actually useful; this is likely to happen only once the first rejuvenation therapies arrive.
Secondly, the research community generally moves slowly in establishing consensus of any kind: the more complex an issue (and biomarkers are complex), the slower progress in reaching a broad agreement is likely to be.
The paper mentioned at the start of this article highlights these points, and given the size of the task it could be a while before we see true consensus on what selection of biomarkers is best as an accurate measurement of aging. That said, progress will continue, and the pace appears to be picking up as support for rejuvenation biotechnology grows and more therapies move closer to the clinic.
With rapid progress in technology, we may find academia will reach an agreement sooner than the researchers in this paper suggest. Indeed there are innovative companies developing biomarkers such as CellAge, Insilico Medicine and many others, so progress may well race ahead unexpectedly in the near future.
It seems pretty clear that DNA methylation, already considered by many in research as the gold standard of aging biomarkers, will end up as an important part of any biomarker panel. Combined with functional aging metrics like grip strength, gait, balance, endurance, and other biomarkers, this could well form the basis for an accurate way to measure aging and changes to aging from therapies.
LEAF will be announcing some exciting biomarker projects hosted on Lifespan.io in the near future to help drive this process; stay tuned for more news soon. You may like to subscribe to our newsletter to keep up to date with the latest information here.