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Are telomeres the aglets of aging? Why the shoelace metaphor is misleading

Aglets protect your shoelaces

I just finished reading the The Telomere Effect by Nobel laureate Elizabeth Blackburn and Elissa Epel (2017). I was somewhat surprised that the authors still use the shoelace metaphor throughout the book (every chapter starts with a picture of shoelaces) because Michael Fossel, another telomere expert, despises the metaphor...

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  • Profile picture of Michael Pietroforte

    In my last post, I outlined David Sinclair’s anti-aging levels 1 and 2. Whereas levels 1 and 2 can, at best, slow the aging process, level 3 has the potential to provide a real cure for aging. At level 3, at least in theory, we can completely reverse the age of an entire organism by introducing the Yamanaka factors.

  • Nice! I know Aubrey but I have never read about his theory in detail, only very superficially. I agree that the Yamanaka factors seem to be the most promising ones. They are also the most exciting ones, the idea of reversing aging is just amazing! I’m not old, I’m 27, but even at my age I think the only possibility of having a very long lifespan is if there is some sort of rejuvenation therapy like this one. Otherwise, I believe it’s too late haha I’m looking forward to your post on the Yamanaka factors.

  • Profile picture of Michael Pietroforte

    I think what he says about stress is consistent. Stress causes damage which causes aging. Moderate stress makes cells hunker down and focus on repairing damage. Thus, moderate stress slows aging, too much stress accelerates aging. Where I can’t follow is his claim that energy costs prevent cells from repairing damage.

    Of course I know Aubrey de Grey. I guess everyone who is interested in the biology of aging does. I have even more problems with his theory that damage caused by metabolism (in particular in the mitochondria) is the main cause of aging which is the old view that more and more gerontologists seem to abandon now. I feel that Sinclair is with his focus on the epigenome more on the pulse of cutting edge anti aging research.

    I don’t think that Sinclair’s research is less practical. In my next post I will blog about his attempt of using some of the Yamanaka factors to reset the clock of aging which is currently the most promising approach in this field.

  • Yeah, I’m reading the book and I didn’t understand his argument in the beginning. This is why I looked for an explanation and found your website. It seems a little contradictory indeed because it is not the damage itself that causes aging but the lack of sirtuins in the epigenome. So I found it really weird when he said that putting more stress in the body would have the effect of increasing aging. It seemed counterintuitive, but so many things in science are. After I finish the book and review his theory I will be able to make a better judgment of his theory, I guess. What do you think about Aubrey de Grey? Do you know him? His causes of aging are different from the hallmark causes that Sinclair says that the scientific community agrees on. de Grey has a more practical approach, focused on solving the problem of aging with biotech, whereas Sinclair (and I suspect the rest of the field) is more into biochemistry.

  • Profile picture of Michael Pietroforte

    I don’t understand where you see a contradiction in my argument. It goes like this:

    1. If Sir2 doesn’t find its way back, the cell can no longer replicate.
    2. Building an extra Sir2 that replaces the missing one would allow the cell to replicate again.
    3. But Sinclair claims that building an extra Sir2 would cost too much energy which is why we don’t see yeast cells with this ability in nature.

    My question is if Neo-Darwinism is correct and evolution is all about replication, how can it be too expensive to create just one extra protein if this this keeps the so important replication process going?

    You are right, the fact nobody did the math does not make Sinclair’s claim wrong. However, because this theory seems so implausible, I wish someone tested this claim empirically. All you have to do is engineer yeast cells that build more Sir2 and see if those cells replicate more efficiently than normal yeast cells. Provided that both cell colonies receive the same amount food, if the engineered cells replicate faster, claim 3 would be falsified and Sinclair’s theory would be in trouble.

  • Profile picture of Michael Pietroforte

    There are only a couple of scientists doing research with sirtuins in yeast and I doubt that they have interest in disproving Sinclair’s claim about the energy costs.

    The argument about the conditions in primordial times is not valid because if building more Sir2 would bring and evolutionary advantage, yeast would have adapted since then.

    The main reason why I find this very common claim about the additional cost for repairing damage implausible is that there are always times when plenty of food is available and organisms could use this additional energy to repair all the accumulated damage thereby reversing their age. That more available food makes most animals age faster, is one of the many empirical facts that make wear-and-tear theories of aging implausible.

    Don’t get me wrong. I am a big fan of Sinclair’s work. I think he is a brilliant experimentalist. Sometimes I just have problems following his more theoretical conclusions.

  • Yes, I agree with you. There should be experiments to test if the energy cost is the same or if it is higher. If it is the same, then the theory is in trouble. If it is a little higher then I believe the theory still stands, considering that primordial earth wasnt a place full of resources (according to him).

    But I believe there is more to it. I’m not a biologist or biochemist, so I dont know how to devise an experiment to disprove his ideas. But I guess somebody would have done it by now if it was that simple.

    Anyway, I still think his theory deserves a lot of credit because it has produced empirical results in some life forms. He had an idea and this idea generated many experiments whose predictions were confirmed. I see that as a big win so far. As for possible shortcomings, there are certainly a few, there is always. Still I think his research is very promising.

  • “First, why don’t cells simply make more repair enzymes? For instances, if Sir2 doesn’t sometimes find its way back to its original position, why not simply make more Sir2? In fact, Sinclair has shown that adding an extra copy of SIR2 increases the lifespan (the number of divisions) in yeast cells (p. 48).”

     

    -It is you who is contradicting yourself here. You just said that he said that adding an extra copy of SIR2 increases the lifespan. As for the other questions:

    “But did anyone really do the math here?”

     

    -Maybe not yet, but this does not mean it is wrong.

     

    “What exactly would be the biological advantage if a yeast cell can create more copies of its DNA because it lives longer?”

     

    -Apparently none, this is why they don’t create more copies.

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