Improved Approaches to Messing with Metabolism Will Use Gene Therapies

I see that noted geneticist George Church has been discussing his new company Rejuvenate Bio in the media. The projects undertaken there are the logical progression of attempts to slow aging with pharmaceuticals, moving them into the era of gene therapy. This is still guided by the a philosophy of what Aubrey de Grey would call “messing with metabolism.” This means that researchers are attempting to alter the amounts of specific proteins in ways that adjust the operation of metabolism into what is hopefully a more optimal state, one in which cell and tissue damage, or the consequences of that damage, accrue more slowly. Gene therapies are far more effective tools than pharmaceuticals when it comes to achieving this outcome with minimal side-effects, and there are many candidate genes to explore.

This is not, however, likely to be as effective as repairing the underlying damage that causes aging. It is tinkering with the broken state of metabolism that arises due to damage, trying to make it more functional without addressing the root cause of its problems. Clearly it is possible to do useful things via this approach, as demonstrated by the existence of statins, first generation stem cell therapies, and the like, but all of these technologies are in principle very limited in comparison to what might be achieved by reversing the root causes of aging.

Professor George Church of Harvard Medical School has co-founded a new startup company, Rejuvenate Bio, which has plans to reverse aging in dogs as a way to market anti-aging therapies for our furry friends before bringing them to us. The company has already carried some initial tests on beagles and plans to reverse aging by using gene therapy to add new instructions to their DNA. If it works, the goal is ultimately to try the same approach in people. “Dogs are a market in and of themselves. It’s not just a big organism close to humans. It’s something that people will pay for, and the FDA process is much faster. We’ll do dog trials, and that’ll be a product, and that’ll pay for scaling up in human trials.”

Church and the team also understand that developing therapies that address aging in humans and getting them approved would not be so easy. It would take too long to prove something worked. “You don’t want to go to the FDA and say we extend life by 20 years. They’d say, ‘Great, come back in 20 years with the data.'” So, the team has taken a different tack; rather than aiming to increase human lifespan as its main focus, it is instead focusing on the typical age-related diseases common to dogs. The hope is that by targeting the aging processes directly, these diseases could be entirely prevented from developing. If successful, this would lend additional supporting evidence that directly treating aging to prevent age-related diseases could also work in humans.

The lab has been working on a collection of over 60 different gene therapies and has been testing their effects both individually and in combinations. The team intends to publish a report on an approach that extends mouse lifespan by modifying two genes that protect against heart and kidney failure, obesity, and diabetes. Professor Church has commented that the results of this study are “pretty eye-popping”. The new startup has been contacting dog breeders, veterinarians, and ethicists to discuss its plans for restoring youth and increasing the lifespan of dogs. Its plan is to gain a foothold in the pet market and then use that as the basis for moving therapies to people.

Link: https://www.leafscience.org/new-harvard-startup-wants-to-reverse-aging-in-dogs-and-then-humans/

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