Shortening telomeres are known to silence nearby gene expression in cells via TPE which would explain why cells stop expressing youthful genes. However are you suggesting that if the cell is exposed to transcription factors eg, those found in young blood it would rejuvenate the telomere length too?
If this was the case that would mean the telomeres would in theory cease silencing youthful genes nearby via TPE and allow adjacent cells to express the genes previously being silenced. In other words a return to youthful function.
This would suggest Telomeres act more akin to a time based gene retarder than a conventional clock as some believe. So as they shorten they begin silencing gene expression which then leads to an older environment and the spiral continues downwards as SASP then starts to be transmitted and the environment becomes more unstable.
If this is the case then increasing telomere length to reinstate youthful gene expression and clearing out the old milieu could bring about rejuvenation.
The problem I see in using mice is their telomere mechanics are not the same as ours which is why I believe intervention with our telomeres would bring much more impressive results. Now if telomere length can be increased via natural transcription factors in young plasma rather than gene therapy eg, TERT activation via AAV that would be very profund indeed. It would suggest that a course of HPE could considerably regnerate the body.
From: Dr. Harold Katcher To: Gerontology Research Group Sent: Tuesday, 17 March 2015, 1:32Subject: Re: [GRG] Combined Therapies mTERT + Plasma
That’s a really good question and one I tried to answer in my 2013 paper (I don’t publish much). My conclusion based on the work of Lapasset is that if you rejuvenate a cell – using transcription factors to change them (some) to induced pleuripotent cells- not only does their mitochondrial functioning return to normal and they stop producing ROS but their telomeres grow long again (and experiments have shown that the procedures didn’t select for long telomered cells to be induced to pleuripotence. My conclusion is that there’s no mechanism preventing telomerase from lengthening telomeres – other than the body signals not to do so. None of this damage is other than purposeful. My solution is to convince the body that’s its young again, and it will act accordingly (to oversimplify a bit). That shortening telomeres cause many age-related conditions I have no doubt – but I think it’s long known that the strict “end-replication problem’ to explain replicative
senescence as envisioned by Olivnikov, where each cell division shortens the telomeres isn’t the truth – or at least it isn’t the way it has to be.