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.



Will Repair Biotechnologies be looking to rejuvenate thymuses in Dogs via gene therapy?

Posted by: jim at May 15th, 2018 9:14 AM

Sounds like a plan.
Is there something like 23andme for dogs or cats? I expect owners would be interested for both health information and perhaps even lineage. I have a family member who often speculates on the breed heritage of her rescue dog, who seems to me to be very much a French Bulldog, but perhaps my relative is correct in thinking her pet has more exotic ancestry. I'd buy the test for $100 as Christmas gift just to settle the matter.
Domestic dogs might have some interesting genes of the driving endonuclease variety, given the amount of artificial selection they've undergone through the centuries.

Posted by: CD at May 15th, 2018 10:46 AM

@jim: I'm personally more in favor of mini-pigs or non-human primates than dogs for a step up to be closer to humans, but it is hard to say at this point where the animal model landscape will take us. It is so very different for every organ and biological system, and the particulars and peculiarities of the various model options are a deep topic indeed.

Posted by: Reason at May 15th, 2018 10:54 AM

One of the areas of rejuvenation research I would like to see, is gene therapy to reduce the platelet count in most people. I have a platelet count of about 105, but most people have a platelet count 2 to 5 times that amount. I have never had a bleeding problem of any kind, so I am concerned that most people are at greatly increased risk of blood clots, blood vessel plaque and dementia from AD, because platelets are the source of production of APP (amyloid precursor protein) that adds to blood vessel plaque and gets carried to the brain, where in 2 chemical transformations, it becomes Amyloid beta and causes AD. Why don't we attack this problem like we have LDL with statins. Just why are all these medical researchers studying LDL, when they should be studying platelet count, APP and amyloid beta as a cause for dementia and AD.

Posted by: Biotechy at May 15th, 2018 2:05 PM

The platelet genes for researchers to look at for gene therapy to begin with at PAI1 SNP's, APP SNP's, and SERPINE1 SNP's. Lets get started on a solution for too many platelets (an over production of) in human blood streams.

Posted by: Biotechy at May 15th, 2018 2:11 PM

While I don't believe that any 'rejuvenation gene therapy' may exist because ageing is merely accumulation of the damage, gene therapy as a part of rejuvenation biotechnology may be very useful. For example, enhance the cells, give them ability to produce new enzymes, make them cancer proof. Wish him good luck!

Posted by: Ariel at May 15th, 2018 3:27 PM

It is a pity that George Church isn't interested in using gene therapy along the lines of lysosens to introduce enzymes to break down hardly lysosomal wastes.

Posted by: Jim at May 15th, 2018 8:51 PM

"...and the FDA process is much faster."

Nonsense - that is just not true

Vet pharma in the U.S. is highly regulated and has major hurdles that even human pharma does not

Just because a dog is your patient, does not mean that you don't have a lot of other traditional, multi-million $$$, non-human work to get done

Also while people may not mind paying anything for their pet's health, they are very averse to their pets becoming clinical subjects

To keep in mind - just a 3 cents

Posted by: Ira S. Pastor at May 16th, 2018 11:25 AM

when Prof. George Church will publish the results from their work, we will see how much is "messing with metabolism" (like you and deGrey/Sens keep claiming) ... or it is something much more fundamental, that you/Sens seems like cannot comprehend it ...
btw, deGery works for AgeX, that literally has one program "messing with metabolism", but he did not mention that this is the wrong approach in his videos with Michael West ...

try to do a favor to the research community in reverse aging: focus on subjects that you understand, rather than attacking everybody else (except Sens). if you believe their programs are worthless and have no good use, let them be. if you believe that only Sens is the right approach, keep bn them, but let the others alone.

Posted by: xyz at May 19th, 2018 8:48 AM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.