20 replies to this topic

[sub7]

You may be highly inclined to turn it off because the guy engages in so much self-promotion and the interview is very long. But there is definitely some new ideas. Everyone /even QuestforLife? yes even him  ) will find a few new ideas at the least.

 

[sub7]

One question to our experts

In the video they talk about many interventions (supplements, lifestyle changes etc) that can slow down telomere shortening When the interviewer asks "how exactly will it work, will these things reduce the rate at which cells will divide? after all this is the only way you can slow down telomere shortening, no?" he receives no satisfactory answer.

 

So.... can you slow down the rate at which telomeres shorten per year, without changing how often the cells will divide? If so ,what is the mechanism?

 

thanks a lot

[QuestforLife]

I have not watched yet, but as I've seen many of Bill's interviews before, I doubt there will be anything new. But certainly I second the Ops request: everyone that is interested in telomeres (and indeed ageing) should watch Bill Andrew's interviews. He is by far the best telomere researcher in the world, still many years ahead of all his peers. It may seem that he is self-promoting, but basically it is true that no one else is anywhere near him. 

 

I find it disturbing to see such ignorance in the video's comments. Basically, either, this is a new idea, or it will cause cancer. Neither is true. 

 

I will have to watch the video through, but I find it suprising that Bill does not answer your question fully. Of course you can slow telomere shortening without slowing the rate of division. The answer is what Bill Andrews has spent his life pursuing: activating telomerase. I would tend to avoid things that slow the rate of division down (unless that division was elevated by something pathological like an illness) because in doing so you will reduce your body's ability to respond to challenges.  

 

 

[sub7]

I would tend to avoid things that slow the rate of division down (unless that division was elevated by something pathological like an illness) because in doing so you will reduce your body's ability to respond to challenges.  

 

Thanks a lot Quest

 

So would you avoid Rapamycin based on that view of yours?
Not sure if Rapa actually has been associated with a reduction in body's ability to respond to changes...

but then again, does Rapa reduce division rate across both healthy cells or merely some? 

[QuestforLife]

tried rapa for 2 years weekly dosing.

tried evero on and off 

 

Short answer is yes, I would avoid. 

 

Calculation may be different for older folks who are on the cusp of senescence across whole body, when rapa benefits may be worthwhile to stop runaway senescence driven activation of inflammation. 

[sub7]

tried rapa for 2 years weekly dosing.

tried evero on and off 

 

Short answer is yes, I would avoid. 

 

Calculation may be different for older folks who are on the cusp of senescence across whole body, when rapa benefits may be worthwhile to stop runaway senescence driven activation of inflammation. 

 

You had mentioned that before, yes.

Don't want to take too much of your time, but I think this is a very important matter WRT Telomeres, so will please ask once more:

Is it possible to leave the rate of cell division untouched, yet still diminish how quickly telomeres shorten? How can that at all be possible? Would be a huge accomplishment if so... it would mean we can change how cells act during division, which sounds very unlikely really...

[QuestforLife]

Is it possible to leave the rate of cell division untouched, yet still diminish how quickly telomeres shorten? How can that at all be possible? Would be a huge accomplishment if so... it would mean we can change how cells act during division, which sounds very unlikely really...

Yes! This is exactly what telomerase does. During cell division the telomerase protein adds telomere repeats (nucleotide bases TTAGGG) to the existing telomere to make it longer. As telomere repeats are lost on one of the DNA strands each division, this will, in the absence of telomerase, eventually lead to critically short telomeres that prevent further division. If this division arrest command fails and the cell continues to divide, the DNA strands can be torn apart in the wrong place during cell division (because the telomere-less ends of chromosomes are fused together by DNA repair enzymes). This leads to anuploidy, I.e. cells with the wrong number of chromosomes. This is the highway to cancer. But if enough telomerase is present, telomere shortening is fully counteracted by the telomere additions from telomerase. This is what happens in telomerase positive cells, like embryonic stem cells. If we use telomerase activators, the best we can currently hope for is counteracting about about 16% of the shortening due to cell division (using TAM818).

I hope this helps. I am happy to answer these questions. Really the best thing would be to ask Mind if he could get a Longecity interview of Bill Andrews where Dr Andrews could answer questions pre-posed by Longecity members.

[sub7]

I feel so dumb. All along I was thinking in m head "ok so there is telomerase to lengthen the telomere portion of the DNA, but without that, how do we keep telomeres from getting shorter?"

 

However, I neglected to state " ... without telomerase.." in my question. Turns out we have been talking about good old telomerase all along. Got you...

 

Yes MIND, please do interview Bill Andrews.... that'd be awesome

[sub7]

tried rapa for 2 years weekly dosing.

 

 

I absolutely must bring this up
(even though you and I did speak about this before, albeit very  briefly)

 

what on earth may you have experienced that made you stop? Have you detailed your experiences anywhere? If so please link. I consider this highly important because 

 

1) we are talking about pretty much the only item we have at hand that, at least in some mammals, has been shown to extend lifespan... we barely have anything else really

 

2) you are possibly the most dedicated and knowledgeable member here

 

yet you stopped taking Rapamycin.
 

It cannot possibly be because you failed to see results... what criteria have you used? there is not a generally agreed upon metric to assess whether Rapamycin is working... if you found such a yardstick, the world needs to know. If not, how on earth have you gauged (the lack of) results?

 

Or side effects were too bothersome. But that too would be highly surprising, because just about nobody suffers unbearable sides from Rapamycin. What would you even notice other than mouth sores. That is essentially the only widely reported side effect, and I doubt that was enough to make you stop.

 

Man, so puzzling and frustrating really....

[QuestforLife]

You seem to think rapamycin is a panacea against ageing, it is not.

 

At the age of 38-40 I found the benefits not to be noticeable other than some very short term effects. At anything more than 2mg/week I got side effects. This was in the form of skin infections as has been reported by Dr Alan Green as being the most common (serious) side effect in his patients, requiring antibiotics and cessation of rapamycin. Everolimus was no better; it did not enable higher doses because of its faster clearance, which proves that it is the peak inhibition of mTOR that matters. 

 

It is also obvious that there is a limit on mTOR inhibition because of its effects on dividing cells. I noticed thinning hair on astaxanthin, another mTOR inhibitor (for example). Consider what rapamycin will likely be doing to your sperm generation (if you are a guy). Whereas telomerase activators give you thick hair. 

 

And consider Blagosklonny, the 'poster child' for rapamycin, had a stroke and got cancer. 

 

As for the effects in mice, they have mTOR jacked up to max, humans are not the same, though as I said, some older humans may benefit. 

 

The short answer is I listen to my body. If something makes me feel worse, I stop taking it, regardless of results in mice in a lab. 

Edited by QuestforLife, 29 October 2024 - 08:56 AM.

[sub7]

You seem to think rapamycin is a panacea against ageing, it is not.

 

I absolutely, definitely do not think that at all. You are fully misinterpreting my position on this matter. I am taking the following stance:

Do the benefits outweigh the costs? If the answer is yes and this thing can even ever so slightly reduce a few symptoms of aging, I am interested. Pls note what I said "ever so slightly" and "reduce"(as opposed to fully eliminate). For example, if there was any substance that, say for argument's sake, could keep my bone density higher into my 80s and did absolutely nothing else, and side effects were very mild to non-existent, I am interested. What I am describing here is not even close to being a panacea, but I would be in.

Next step is cost and availability. If the positives very slightly outweigh the negatives and I can afford as well as obtain it, I am in.  This line of thinking may not apply to all members here and some may only be interested in using an item is indeed a panacea. I am not one of them.

 

Now that we finally got this out of the way, I am very glad you shared your experiences because I consider your views very important. I still disagree that you would have seen anything noticeable as far as benefits (I can very much see something slowing down aging mildly and providing no observable benefits. While taking some item, Rapa or something else entirely, you maybe just aging at a slower rate throughout all tissues, and notice nothing at all as a result. That is totally comprehensible. After all, aging itself is a fairly slow process and a mere slowdown in such a process would be extremely difficult to observe)

However, the skin infection issue and the thinning hair are yes, problematic and I will be keeping them in mind as I go along.

Appreciate the input

[QuestforLife]

I've asked Mind what he thinks about asking Dr Bill Andrews for an interview.

 

 

[sub7]

I've asked Mind what he thinks about asking Dr Bill Andrews for an interview.

 

Well done Sir!

[QuestforLife]

I absolutely, definitely do not think that at all. You are fully misinterpreting my position on this matter. I am taking the following stance:

 

 

I intended no disrespect. We differ on this point, but nevertheless it is good that different self-experimenters take a different stance as it gives us more data points.

 

I, for one, whilst placing an emphasis of importance on telomeres, do not believe they are the sole answer to solving ageing. After all, it is possible mice telomeres do not shorten at all, but they still age and die, primarily by another mechanism. I believe that maximum lifespan in humans is however enforced by telomere attrition.

[sub7]

I intended no disrespect. We differ on this point, but nevertheless it is good that different self-experimenters take a different stance as it gives us more data points.

 

I, for one, whilst placing an emphasis of importance on telomeres, do not believe they are the sole answer to solving ageing. After all, it is possible mice telomeres do not shorten at all, but they still age and die, primarily by another mechanism. I believe that maximum lifespan in humans is however enforced by telomere attrition.

 

Oh no offense taken; no worries.

I have been convinced long ago that yes, attacking the Telomere shortening problem is worth attacking with vigor for life extension and also that this alone will not solve the whole problem. Agree on both counts.

 

Since I have you here, can I follow up on one quick thing?
So when Dr Andrews says that Vitamin D may slow down telomere attrition (or maybe we should put it another way: insufficient / suboptimal vitamin D levels accelerate telomere attrition ) is this through Telomerase activation? i.e. there is always some degree of telomerase activation during cell division, but the degree of such activation is not enough to eliminate the shortening of the telomeres. However this natural / background activation does help a little. If there is insufficient Vit D levels (or any of the other things that may accelerate telomere shortening) even this little bit of telomerase activation does not happen and telomeres shorten at an even more accelerated rate.

 

Is that more or less it?

[QuestforLife]

Yes, Vit D activates telomerase (extremely weakly), as does fish oil. 

[sub7]

Yes, Vit D activates telomerase (extremely weakly), as does fish oil. 

 

OK that works now   
Many thanks

[QuestforLife]

BTW I have watched the full interview now.

 

There is a lot covered: his views on the evolution of ageing (still quite a minority view), lifestyle factors (I see why you were confused sub7; he also discusses limiting inflammation and oxidative stress than can shorten telomeres at an accelerated rate, independent of telomerase), his work with Liz Parrish (I was not aware of the full extent of this), his robotic assay for finding hTERT RNA expression, his view (shared by me) that telomere tests are not good enough and that glycanAge is better, and his views on epigenetics being a misnomer and actually what you need is a full RNA sequence. He also talks about the telomere effect (how the telomere loops back and influences gene expression across the chromosome), meaning lonng before cellular senescence the cells are gradually 'getting old', the complexities of telomerase repression (he effectively gave up on this and instead has tried to brute force a solution: possibly a mistaken given the cost). I have looked at his websites in the past, and even suggested Longecity licence one or more of his nutraceuticals (they aren't very expensive, you just have to pay him royalties). But I wasn't aware that touchstone essentials had done this and will be selling a combination of some of his more powerful telomerase activating nutraceuticals in 2025. 

 

Only one point of his I take issue with: he is of the opinion that exosomes/plasma exchange causes regeneration by entirely non-telomerase mediated mechanisms. But we now now exosomes can carry the telomerase protein and deliver this into cells. I think this is a very viable alternative to gene therapy, which is not yet safe or effective (IMO).

 

Any questions on the above, or anything I forgot to mention here, let me know.

[sub7]

Thanks a ton for sharing your views / observations Quest

His idea of the DNA folding over and the telomeres - during this process- coinciding with certain parts of the DNA and impacting its expression is amazing. Is that solely his view or does it have other believers / indirect proof of it too?

 

Can you explain this " the complexities of telomerase repression".  As in cells that could express telomerase stop dong so? If that is the case, did you mean steps to eliminate this repression may prove to be fruitful? Maybe I totally misunderstood....

 

[QuestforLife]

No one knows exactly how telomere length regulates gene expression, but the telomere position effect (over long distance) has been proven for a few genes. The work was done by Shay and Wright, I've posted the papers to my thread before.

Repression is complex because the HTERT gene has several promoters and repressors (probably) so there are numerous things you have to do to get HTERT turned on fully.

[QuestforLife]

https://www.longecit...r-bill-andrews/

 

Interview questions for Dr Andrews