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

[jocko6889]

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/

[Fred]

Interesting! Thank you. Love his blog (must check it more often). The comment section is gold. Real scientists giving their view, debating like they would at a conference perhaps.

[jocko6889]

Fred, I agree. Josh Mitteldorf has a great blog. I've learned a lot from him and the comment section as you point out is very good.

[drkris69]

Thanks jocko will start checking this out.

[Newage]

Thanks jocko will start checking this out.

Yes jocko..thanks.
A great blog that I wasn’t aware of.
I will be a constant follower from now on. The blog contains informative feedback of a high standard with no aggressive undertones..

[canadahealthy]

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/

jeebus, i gotta learn a whole new vocabulary.

but in an nutshell, methylation is a process of reversing the 'age' of a cell??

[Fred]

Methylation and demethylation are chemical processes/reactions that the body uses. It's not the process of reversing a cells age.

Measuring the rate of these reactions at certain sites can predict when you will die. See Horvath's clock or epigenetic clock here:

https://en.m.wikipedia.org/wiki/Epigenetic_clock

METHYLATION
"In biological systems, methylation is accomplished by enzymes. Methylation can modify heavy metals, regulate gene expression, RNA processing and protein function. It has been recognized as a key process underlying epigenetics. The Methylation cycle in medicine relates to the metabolism of various systems including DN and the production of glutathione. Faulty methylation cycle has been related to various abnormal conditions including Myalgic Encephalomyelitis (ME CFS)"

https://en.m.wikipedia.org/wiki/Methylation

[jocko6889]

jeebus, i gotta learn a whole new vocabulary.

but in an nutshell, methylation is a process of reversing the 'age' of a cell??

It's the opposite. Methylation on the epigenome ages a cell. Stem cells have no methylation and are called "undifferentiated cells", so some methylation is required to cause cell differentiation (heart cell versus a liver cell, brain cell, etc). A methyl group is required to activate a gene. The problem comes in when we acquire too much methylation and too many genes are activated, sometimes the wrong ones, which is what aging is. Poor diet, too much sun, smoking, xrays can all add excess methylation and age us prematurely but just existing and time will cause some methylation. Currently the only way to reverse this process is the method recently outlined by Sinclair in his book, using 3 of 4 Yamanaka factors to partially roll back the accumulation of methylation on the epigenome. The body soon follows, rolling back in time according to our DNA blueprint.

[Drdavid]

These are interesting questions and ones that should be answered by the scientists that did the research. Whether it was intentional or simply an oversight these questions must be answered. Variability will kill a research project and leaving out specific data sets causes questions about the entire research.

[canadahealthy]

That blog is amazing. I am struggling through the comment section but have already added Boswellia extract to my list.