Fight Aging!

The typical path for any program in biomedical research and development is to first demonstrate interesting results in animal studies using forms of genetic engineering or gene therapy, and then find small molecules that adjust the same mechanism. Small molecules are never as good as genetic manipulations, the size of the effect is always smaller, usually much smaller, and there are inevitably side-effects. Small molecule development is much easier to conduct, however, more familiar to investors and regulators and program managers, a well-trodden path. Thus while the future of medicine is gene therapy, in search of large effect sizes and no side-effects, the present industry remains near entirely focused on small molecules. Given the popularity of reprogramming as an approach to treat aging, an increasing number of research groups and companies are working to find small molecules that induce reprogramming to some degree, an alternative to gene therapies that induce expression of the Yamanaka factors. Based on the discoveries to date, it seems plausible that they will succeed.

Two weeks ago, longevity biotech startup Clock.bio emerged from stealth with $4 million in funding, and setting itself an ambitious goal to be in a Phase 3 trial for a healthspan-extending intervention by the end of the decade. With the clock ticking, the company is already working to map rejuvenation biology across the entire human genome over the next 12 months. Having completed an initial screen of around 1,000 genes, Clock.bio says it has already identified several new potential rejuvenation targets.

The company is based on the idea of triggering the self-rejuvenation mechanism of pluripotent stem cells to gain insight into the cellular drivers of aging and rejuvenation. Crucially, Clock.bio has found a way to shortcut the screening process required to identify rejuvenation drivers across the entire human genome. "We have been able to create a paradigm in the lab, where we override the repair programs, and force-age the stem cells, so that their rejuvenation capabilities kick in again." The company uses unbiased CRISPR screens on large samples of stem cells to identify gene candidates that are causally relevant for cell rejuvenation.

Clock.bio then identified some existing, approved drugs that could potentially be used against the targets identified in the first screen. "We looked at whether these drugs could beneficially modulate aged neurons - we found that they did, and if we combined them the results got even better. So, now we have this end-to-end validation in vitro - from being able to identify rejuvenation genes, which are essentially controlling repair processes, through to activating those repair processes in aged cells. It's a completely unbiased way to understand every process that's involved in restoring the aging hallmarks."

Link: https://longevity.technology/news/the-quest-for-rejuvenation-without-reprogramming/