Short In Vivo Reprogramming Treatment Reverses Age-Related Omics Changes in Mice

Researchers here demonstrate that, in mice, many biological markers of aging (in the epigenome, transcriptome, and metabolome) are made more youthful by a short in vivo exposure to the Yamanaka factors capable of reprogramming cells into induced pluripotent stem cells. That process also resets epigenetic marks on the genome to a youthful configuration, improving mitochondrial function, among other benefits. In this case, the goal of a short treatment is to minimize any possible cell conversion, keeping the reprogramming exposure short enough to only change epigenetic markers, gene expression, and cell behavior to be more youthful. The primary challenge in bringing this class of therapy to the clinic will be the long-term safety questions, how to assess (and then minimize) the risk of cancer via unwanted pluripotency of cells, when the consequences of that risk might take years to become visible in humans.

The expression of the pluripotency factors OCT4, SOX2, KLF4 and MYC (OSKM) can convert somatic differentiated cells into pluripotent stem cells in a process known as reprogramming. Notably, cycles of brief OSKM expression do not change cell identity but can reverse markers of aging in cells and extend longevity in progeroid mice. However, little is known about the mechanisms involved. Here, we have studied changes in the DNA methylome, transcriptome and metabolome in naturally aged mice subject to a single period of transient OSKM expression.

We used the reprogrammable mice known as i4F-B which carries a ubiquitous doxycycline-inducible OSKM transgene, abbreviated as i4F. Mice of both sexes were used, and of different ages; young (females, 13 weeks), old (females, 55 weeks) and very old (males and females, 100 weeks). Doxycycline was administered in the drinking water for a period of 7 days. Mice were sacrificed two or four weeks after doxycycline removal.

We found that this is sufficient to reverse DNA methylation changes that occur upon aging in the pancreas, liver, spleen, and blood. Similarly, we observed reversion of transcriptional changes, especially regarding biological processes known to change during aging. Finally, some serum metabolites altered with aging were also restored to young levels upon transient reprogramming. These observations indicate that a single period of OSKM expression can drive epigenetic, transcriptomic and metabolomic changes towards a younger configuration in multiple tissues and in the serum.



You are a group of highly educated and dedicated to your cause which is admirable.
Everyone is talking about aging but no one is talking about how to help the aged. How to remove or reduce Amyloid buildup. Inflammation is the mother cause of most disease.
All these scientific jargon and talks are all good but doesn't help a person with no medical background. Let's also find a way to help our older generation to live a dignified life in their old age. Looking at your ages you all must have and older family member whom is very dear to you. You cannot tell an eighty year old person that you are trying to make him live to 135. He needs something now that can make his life easier and more independent until the day he passes on.
I wish you all the best and looking forward reading all of your research results.

Posted by: Chamsi Brown at January 28th, 2022 8:41 PM

Smart... they killed the mice before they could develop teratomas.

Posted by: Jones at January 29th, 2022 6:41 AM

I hope there are multiple long terms studies of this treatment going on in Monkeys right now.

Posted by: jimofoz at January 30th, 2022 9:25 AM

that helps to shorten the publication cycle. And then get grants for longer term study for actual clinical improvement. Don't hold your breath, but if you manage not to die in the next 30 years this one might become a viable treatment. If we are lucky it might be 15 years.

Posted by: Cuberat at January 30th, 2022 3:47 PM

Are the changes being reversed caused by glycation and advanced glycation end products?

Posted by: Dennis at January 30th, 2022 11:31 PM

@ Chamsi Brown, regarding the removal of Amyloid buildup, you may want to check out the AMBAR treatment ( and google to see when it will be available in the United States (it just rolled out in Spain). The spice Tumeric has also been shown to help reduce the inflammation caused by Amyloid build-up. You can google science articles related to that (too many to list here). Regarding your sentiment about how this treatment doesn't help the aged, that's exactly what it's supposed to do. If you are able to return your genes (genome) to a younger version of themselves, you have turned back aging and the diseases that go along with aging (heart disease, cancer, Alzheimers, Type 2 Diabetes, etc). You may wish to read Dr. Sinclair's book "Why we age and why we don't have to" for an introduction into the science of aging and how research like what you see above is going to be one of the most important things to happen to humanity in the next 50 years. Dr. Sinclair is a co-director of the Biology of Aging Research at Harvard Medical School. I think you'll really enjoy the book and I would pay special attention to how Dr. Sinclair's Father has changed (anecdotally) with the introduction of some anti-aging compounds. If you don't wish to read the book, then I would suggest watching the first couple of episodes of Dr. Sinclair's Lifespan Podcast which you can also find on YouTube on the channel "David Sinclair".

Posted by: Matt at January 31st, 2022 6:42 AM
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