Gene Therapy Mediated Partial Reprogramming Extends Lifespan and Reverses Age-Related Changes in Aged Mice

I know that this was originally posted in January 2023, but I don’t remember seeing much of it around.

I am myself not that much of a fan of using the Yamanaka factors.

They used old mice at 124 weeks and found that the controls lived (median) to ~133 weeks and the treated to 142.5

Which is 109% increase of the lifespan since 124 weeks, but otherwise a 7% increase.

To be honest one reason why I think this has not got a lot of publicity is that Rapamycin has a greater extension of lifespan although I don’t know about the specific situation of taking progeroid mice and intervening at a really late stage.

My view on the reprogramming is that its main effects lie in SOX2 (or some other gene) encouraging autophagy.

Also " We isolated DNA from heart and liver tissue from control and TRE-OSK treated mice at time of death and found that the Lifespan Uber Clock (LUC) for both liver and heart trended towards reduced epigenetic age "

Which given that the mice had died to some extent undermines the idea of the aging clock as measuring mortality.

However, I thought people would be interested to see this if they haven’t already done so.

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IMO this is important, if incremental progress, in two respects. First, it shows viability of gene therapy (a lot of the previous work uses transgenic animal). Second, it actually shows life extension in normal-ish mice. Which is unusual – many partial reprogramming approaches don’t extend life, for whatever reason.