Longevity ⇒ Unanswered Questions Remain from Sinclair's Recent Epigenetic Mouse Experiments

[AlbertY]

In this article by Josh Mitteldorf, he claims there remain unanswered questions from Sinclair's recent Epigenetic mouse experiments and whether Sinclair has in fact told us everything.

For example, in Sinclair's experiment to reset the mouse epigenome in the optic nerve, 3 of the 4 Yamanaka factors (OSK - the first 3 out of the 4 Yamanaka factors OSKM), administered in short pulses, were used to set back the Horvath methylation clock without turning functioning tissues back into stem cells or inducing cancer.

"But they also report a “safety” test done, in which OSK was induced in the whole body at a low level for an entire year without toxic effects. Of course, it’s nice to know that the low-dose OSK was not toxic and that cancer risk did not increase. But did the mice benefit from the whole-body treatment? Did they show any signs of rejuvenation, or of enhanced stem cell function?

There is a Horvath methylation clock for mice. Did the mice get younger according to the Horvath clock? The authors report that damaging the retinal nerve made the nerve cells older according to the methylation clock, and that the application of OSK brought the cells back. But I don’t see anywhere in the paper a measurement of the eye’s methylation age before and after the OSK treatment, independent of injury. For that matter, there is no discussion of the methylation age of the mice treated with whole-body OSK for a year. These omissions are curious. Are they suspicious? Have they tried and failed to set back the methylation clock, and they don’t want to report it?"

For more, click the link below:

https://joshmitteldorf.scienceblog.com/ ... genic-age/

I actually know some answers. For the whole body OSK experiment, I can only tell you the experiment wasn't designed very well and not very informative, we need to redo it. For the methylation age of the nerve before and after the OSK treatment, independent of injury. It is because the nerves are from young mice, it is hard to tell the effect OSK without injury. Injury is needed because it can accelerate methylation age, so after injury (increasing methylation age) the rejuvenating effect of OSK became obvious.