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Optimizing DNA repair mechanisms seem to be key. here. I think it was Vera Gorbunova highlighted (in a recent talk) the importance of Sirt6 in repair of double strand DNA breaks, which appears to be a a major source of mutations.
Thanks, I couldn't recall who, but I remember seeing a doctor/researcher explain double strand breaks. Also Dr Mobeen Sayed discussed it -but wrt a recent 'vaccine SP in the DNA' in-vitro study IIRC.
Hi Peter thanks for sharing. Agree, I don't think you can reduce the damage much, but upregulating the repair systems would make sense. Sirt6 is part of the story but I think the other SIRTs and PARPs are also involved, all of which require NAD.
@@ModernHealthspan Sirts don't work by themselves, but in concert. Sirt1 + Sirt6 together regulate genetic repair. SIRT1 is an accessory oscillator protein that's part of a dual feedback loop linked to circadian rhythm. Multiple oscillators that coordinate differentially. “Pacemaker” and “Slave” oscillators. Some react to environment, some to day night cycles, some to nutrients. It's like tuning a stereo equaliser, but an equaliser that is constantly on the move in response to environment stressors, day night cycles, and nutrient stresses. Slamming the foot on the accelerator of any one for too long would probably be a bad idea, as they are supposed to be circadian and differentially mediated. Growth phase and repair phase, with overlapping adaption to environment and nutrient phases.
Very interesting, thanks for sharing! One curious question, do you have any video on what supplements you take? For example if you take rapamycin and on what dose regime etc?
My first chat with Aubrey deGrey in 2006 was on this very subject, although at the time I speculated that the high mutation rate in mice contributed to the relatively high impact of longevity interventions which would not be easily replicated in humans as we already have high efficiency cancer suppression mechanisms. He agreed, on reflection that may have been because he wanted me to buy the beer.
Love this study - thanks for sharing it. I do worry that the wrong lesson will be learned here - because I strongly suspect the key to longevity is not so much preventing mutations, but in correcting them when they happen. The cellular epigenetic processes that fix mutations should be strengthened with mitophagy and mitochondrial health support, and possibly with senolytics and other approaches currently being researched to remove over-mutated/old cells quickly and keep the per-cell mutation rate down.
Interesting, and I'll look into the unfamiliar. I've been eating anti-carcinogenicaly and for optimal health since 1978. But now that my wonderful wife's been diagnosed with cancer I need to expand the types of studies I read. There's always so much to learn.
@Paul Wolf There's a recent youtube video by Today's Sciencology which discusses latest dna repair research, but you can't seem to link in youtube responses or they don't post.
Hi Ken, thanks for sharing. I agree with you. DNA is pretty much the same across all mammals and I would think that it has the same kind of stresses and the same amount of damage. It is whether the repair machinery can fix the breaks afterwards that makes the difference. So maybe raising NAD is one of the keys as the repair proteins, SIRTs and PARPs are all dependent on NAD for their work.
Even if mutation rate determines lifespan, we don't really know whether given our current biology it is determining a maximum average of 80, of 120, or of 160 or something else. One can imagine a maximum age of 160 based on a random process being associated with a 1% to .1% selection pressure as exposed at age 40 that drives adaptation over long periods.
Hi Jeff, thanks for sharing. I agree. We could use the mutation rate to estimate the "expected" lifespan, but it does not really tell us the maximum. Part of the theory is that the accumulated damage would lead to organ failure, but what if you have organ transplants? Or the ability to regrow your organs from harvested stem cells?
This is an interesting study, but mutations causing aging was described by Aubrey de Grey over 25 years ago. It is one or two of this Seven Deadly Things, 1.) "mutations" and 2.) "division-obsessed cells". These are well-outlined in his book Ending Aging.
Hi Graham, thanks for the comment. There are a number of theories of aging which involve damage, and this is one of them. The theory is not new, what this paper does provide is the data to back up the theory which was not available before.
A galaxy of observations does not afford a cosmology. I am inclined to live simply, within the known bounds, rather than aspire to some, as yet, arcane key. My health is good my age is exceptional, my interests are many. What more could one need?
Hi Christopher thanks for sharing and great to hear. I am with you. I am not waiting for some wonderful future but following what we know now to live as well as I can.
If you would like to support our channel, we’d love a coffee ☕…thank you! www.buymeacoffee.com/mhealthspan
Renue By Science 10% of all products: tinyurl.com/2c28d6er
Bulletproof 15% off with coupon code: HEALTHSPAN15: bulletproof.fdf2.net/c/3176409/551222/9221
Optimizing DNA repair mechanisms seem to be key. here. I think it was Vera Gorbunova highlighted (in a recent talk) the importance of Sirt6 in repair of double strand DNA breaks, which appears to be a a major source of mutations.
Thanks, I couldn't recall who, but I remember seeing a doctor/researcher explain double strand breaks. Also Dr Mobeen Sayed discussed it -but wrt a recent 'vaccine SP in the DNA' in-vitro study IIRC.
Genetic repair can cause epigenetic drift. So you have to stabilise epigenetic drift at the same time as upregulating genetic repair.
Hi Peter thanks for sharing. Agree, I don't think you can reduce the damage much, but upregulating the repair systems would make sense. Sirt6 is part of the story but I think the other SIRTs and PARPs are also involved, all of which require NAD.
@@ModernHealthspan Sirts don't work by themselves, but in concert. Sirt1 + Sirt6 together regulate genetic repair.
SIRT1 is an accessory oscillator protein that's part of a dual feedback loop linked to circadian rhythm.
Multiple oscillators that coordinate differentially. “Pacemaker” and “Slave” oscillators. Some react to environment, some to day night cycles, some to nutrients.
It's like tuning a stereo equaliser, but an equaliser that is constantly on the move in response to environment stressors, day night cycles, and nutrient stresses.
Slamming the foot on the accelerator of any one for too long would probably be a bad idea, as they are supposed to be circadian and differentially mediated.
Growth phase and repair phase, with overlapping adaption to environment and nutrient phases.
Very interesting, thanks for sharing! One curious question, do you have any video on what supplements you take? For example if you take rapamycin and on what dose regime etc?
My first chat with Aubrey deGrey in 2006 was on this very subject, although at the time I speculated that the high mutation rate in mice contributed to the relatively high impact of longevity interventions which would not be easily replicated in humans as we already have high efficiency cancer suppression mechanisms. He agreed, on reflection that may have been because he wanted me to buy the beer.
Love this study - thanks for sharing it. I do worry that the wrong lesson will be learned here - because I strongly suspect the key to longevity is not so much preventing mutations, but in correcting them when they happen. The cellular epigenetic processes that fix mutations should be strengthened with mitophagy and mitochondrial health support, and possibly with senolytics and other approaches currently being researched to remove over-mutated/old cells quickly and keep the per-cell mutation rate down.
Interesting, and I'll look into the unfamiliar. I've been eating anti-carcinogenicaly and for optimal health since 1978. But now that my wonderful wife's been diagnosed with cancer I need to expand the types of studies I read. There's always so much to learn.
@Paul Wolf There's a recent youtube video by Today's Sciencology which discusses latest dna repair research, but you can't seem to link in youtube responses or they don't post.
Hi Ken, thanks for sharing. I agree with you. DNA is pretty much the same across all mammals and I would think that it has the same kind of stresses and the same amount of damage. It is whether the repair machinery can fix the breaks afterwards that makes the difference. So maybe raising NAD is one of the keys as the repair proteins, SIRTs and PARPs are all dependent on NAD for their work.
Kind of amazing that we wind up with only 3-4000 mutations per cell when we have 3.2 or 3.5 (?) BILLION pairs / genome.
I wonder whether "mutation" refers to "change in the genome" or "Change anywhere in the DNA"? I suspect the former.
@@jefflittle8913 good point
Even if mutation rate determines lifespan, we don't really know whether given our current biology it is determining a maximum average of 80, of 120, or of 160 or something else. One can imagine a maximum age of 160 based on a random process being associated with a 1% to .1% selection pressure as exposed at age 40 that drives adaptation over long periods.
Hi Jeff, thanks for sharing. I agree. We could use the mutation rate to estimate the "expected" lifespan, but it does not really tell us the maximum. Part of the theory is that the accumulated damage would lead to organ failure, but what if you have organ transplants? Or the ability to regrow your organs from harvested stem cells?
I think this works
Hi Ram, thanks for your comment.
This is an interesting study, but mutations causing aging was described by Aubrey de Grey over 25 years ago. It is one or two of this Seven Deadly Things, 1.) "mutations" and 2.) "division-obsessed cells". These are well-outlined in his book Ending Aging.
Hi Graham, thanks for the comment. There are a number of theories of aging which involve damage, and this is one of them. The theory is not new, what this paper does provide is the data to back up the theory which was not available before.
thx Richard for this intresting video.
Hi Abdelilah thanks I hope that you enjoyed it.
Thank you.
Hi Ron, thanks!
A galaxy of observations does not afford a cosmology. I am inclined to live simply, within the known bounds, rather than aspire to some, as yet, arcane key. My health is good my age is exceptional, my interests are many. What more could one need?
Hi Christopher thanks for sharing and great to hear. I am with you. I am not waiting for some wonderful future but following what we know now to live as well as I can.
@@ModernHealthspan yes, start with what is at hand and waive the rest...