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Olshansky - Immortality As Hype, Nothing New


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#61 sjayo

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Posted 02 June 2005 - 03:38 PM

justinb: what proceeds? One does not write books of this kind in order to make money. However, if an HPrize was established, I might consider contributing something. I hope you can figure out what that means.
S. Jay Olshansky

#62 Infernity

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Posted 02 June 2005 - 03:44 PM

Yieks I missed the chat :(

However, I think it was late at night over here at any rate, so never mind.


Yours truthfully
~Infernity

#63 jaydfox

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Posted 02 June 2005 - 04:45 PM

However, if an HPrize was established, I might consider contributing something. I hope you can figure out what that means.
S. Jay Olshansky

Hymenoptera Prize? I don't know, people gave me crap about a Fly Prize, but trying to make ants, bees, or wasps live longer seems like something people might actually fight against. Seems counterproductive to the cause, if you ask me...

[tung]

#64 justinb

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Posted 03 June 2005 - 01:44 AM

justinb:  what proceeds?  One does not write books of this kind in order to make money.  However, if an HPrize was established, I might consider contributing something. I hope you can figure out what that means.
S. Jay Olshansky


I can only guess.... Human? Homo Sapian, Hominoid, etc [lol]

#65 DJS

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Posted 03 June 2005 - 01:55 AM

I believe Justin that this is a veiled reference by Mr. Olshansky that he does not believe that success in mouse life extension will be easily transferable to humans.

Perhaps, perhaps not, but there is no doubt that it would merit a Noble prize.

#66 justinb

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Posted 03 June 2005 - 07:48 AM

I believe Justin that this is a veiled reference by Mr. Olshansky that he does not believe that success in mouse life extension will be easily transferable to humans.

Perhaps, perhaps not, but there is no doubt that it would merit a Noble prize.


I thought the same thing, but I wasn't sure if I was lot of line if I brought it up.

#67 sjayo

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Posted 03 June 2005 - 02:32 PM

DonSpanton and justinb: Successful life extension in mice was achieved decades ago when scientists at Argonne National Laboratory used WR2721 in radiation biology studies to increase life expectancy and maximum lifespan up to 50% (my colleague Bruce Carnes was involved in some of these studies). I think they're still waiting for their Nobel Prize. It's probably not a good idea to put words into someone's mouth with the notion of a veiled reference -- I've certainly never been good at reading minds and you didn't read mine in this case. What I was referring to was not the problem of transferring life extension from other organisms to humans, but the problem of creating a prospective clinical trial using longevity as an endpoint in a long-lived species. I first raised this issue last November at a EMBO meeting in Heidelberg, and again at the American Federation for Aging Research meeting before GSA last year, and the problem remains. This doesn't mean such experiments with humans cannot be done -- it's just that scientists will have to settle for endpoints other than duration of life during most of the study. The fundamental question of radical life extension in humans will not be answered for quite some time. Thus, the Hprize would solve the problem of how to properly conduct and successfully carry out duration of life/life extension studies in humans.
S. Jay Olshansky

#68 DJS

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Posted 03 June 2005 - 02:47 PM

It's probably not a good idea to put words into someone's mouth with the notion of a veiled reference -- I've certainly never been good at reading minds and you didn't read mine in this case.


LOL. Okay? [huh] But it seemed to me as if you were asking for an interpretation by leaving yourself intentional vague. Why didn't you just explain yourself to begin with?

And instead of life extension I should probably have used the term "rejuvination".

#69 sjayo

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Posted 03 June 2005 - 03:43 PM

Don: I'm a teacher -- that's how I get my students to think. In fact, I don't let my students take notes in my classroom, which I consider nothing more than a lesson in transcribing. The process of discovery is every bit as important as the outcome -- dialogue such as ours is healthy. You should see the angst that I see on the first day of class (all graduate courses by the way) when I tell students they can't take notes -- it's as if a crutch has been removed. They recover a bit when informed that they have free access to my notes, but all of our class time is spent with them learning how to think like scientists -- a good lesson I think for newly minted physicians and budding epidemiologists.
S. Jay Olshansky

Edited by sjayo, 03 June 2005 - 10:02 PM.


#70

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Posted 03 June 2005 - 11:56 PM

Successful life extension in mice was achieved decades ago when scientists at Argonne National Laboratory used WR2721 in radiation biology studies to increase life expectancy and maximum lifespan up to 50%


If you are referring to the this study (1), WR2721 (amifostine) increased the lifespan of mice that had been exposed to radiation - the scope of the study did not include animals that were not exposed to radiation. I have not been able to locate any studies where WR2721 was used as a lifespan modulator in a non-radioprotective context. In any case, WR2721 appears to act by mopping up free radicals and may act by inhibiting the p53 response whilst allowing DNA repair to continue so it is very interesting as a non-genetic intervention (even though it would be better from a delivery/therapeutic perspective to emulate its function in the form of a protein). In light of your interest in WR2721 what is your view on genomic damage as a contributor to aging?


(1) Int J Radiat Biol. 1992 May;61(5):567-76.
In vivo protection by the aminothiol WR-2721 against neutron-induced carcinogenesis.
Carnes BA, Grdina DJ.

#71 sjayo

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Posted 04 June 2005 - 03:24 AM

Prometheus: Actually, as I understand it, WR2721 operates less as a free radical scavenger and more as a method of lengthening the cell cycle -- enabling repair to occur for a longer time frame. The studies also included amifostine used on the control animals -- not just those exposed to radiation. It's the control animals that Bruce and I have been mining for decades as fascinating examples of how there is a fundamental link between the timing of reproduction and the duration of life (given the variation in reproductive patterns in the numerous strains used). Every animal in these studies was autopsied by the same pathologist -- histopathology is available on every animal -- think about that for a moment.
S. Jay Olshansky

#72 kevin

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Posted 04 June 2005 - 07:03 AM

Jay:

Successful life extension in mice was achieved decades ago when scientists at Argonne National Laboratory used WR2721 in radiation biology studies to increase life expectancy and maximum lifespan up to 50%


One thing about historical experiments demonstrating lifespan extension is that they really didn't know much about how it was accomplished and thus it was difficult to get excited about the possibility of it being relevant to humans. This is in sharp contrast to recent research efforts. For instance the Rabinovitch et al. paper which demonstrated unambiguously the role of mitochondrial mutations in aging, illustrates the difference in approaches and precision from inception to completion of modern experimentation as compared to historical techniques.

I expect all I'm saying is the same as usual, that historical patterns of even the recent past are not likely to be good predictors of how fast life-extending technologies are developed or adopted due to the radically different way science is being conducted and the speed of discovery.

With all the different technologies being developed for keeping people healthy and alive, and I'm particularly intrigued by cybernetic approaches including artificial hearts and bio-artificial organs as well as rejuvenation with stem cell and gene therapies, I find it difficult to imagine a near term future (say...50 years) where maximum lifespan is not extended dramatically. I felt in the chat that you might not be quite as attached to your assertion that no one alive in 2000 would live to see 2150 as you were when you made your bet with Austad... are there any particular recent discoveries or trends which might help shift your position?

#73

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Posted 04 June 2005 - 07:25 AM

WR2721 operates less as a free radical scavenger and more as a method of lengthening the cell cycle -- enabling repair to occur for a longer time frame


It appears to act on two levels: physicochemically as a hydrogen atom donator and thus as a chemical antioxidant and transcriptionally in its ability to suppress and induce the expression of certain genes associated with apoptosis, DNA repair and, as you mentioned, cell cycle control (1). It also modulates stem cell differentiation (2). A fascinating drug - surprising that in light of its negligible toxicity it has not emerged as an antisenescence agent.

Every animal in these studies was autopsied by the same pathologist -- histopathology is available on every animal -- think about that for a moment.


A good and bad thing (a single pathologist). So what are your conclusions on the histopathology of the control animals?

You did not respond to my previous question: in your view how important is genomic stability in aging? In other words if genomic stability could be increased (by, say, increasing the rate of accurate DNA repair) do you think it would extend lifespan?


(1) Int J Radiat Oncol Biol Phys. 2004 Oct 1;60(2):553-63.
Interaction of amifostine and ionizing radiation on transcriptional patterns of apoptotic genes expressed in human microvascular endothelial cells (HMEC).
Khodarev NN, Kataoka Y, Murley JS, Weichselbaum RR, Grdina DJ.

(2) Acta Haematol. 2004;112(3):136-40
Amifostine stimulates the formation of hematopoietic bone marrow progenitors from B-cell chronic lymphocytic leukemia.
Tsatalas C, Spanoudakis E, Pantelidou D, Margaritis D, Kotsianidis I, Chalkia P, Tripsianis G, Basdiara I, Kartasis Z, Karakolios A, Bourikas G.

#74 John Schloendorn

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Posted 04 June 2005 - 09:07 AM

sjayo: With regard to what science should get funded -- that is quite complicated and would take more time than I have here.

That's cool - I'll try to split it up, just reply to as much as time permits. I'll stop nagging.

sjayo: Huber Warner

Thanks, I'm familiar with that paper. Very goal-targeted and useful. I had it on the list for the imminst journal award, but dropped it because I wanted to put most of the focus on original benchwork. The authors seem to agree with Aubrey's point I was citing (that human rejuvenation may be easier than slowing aging), as far as trialling the interventions is concerned:

paper: If the intervention is expected to reverse in older persons adverse aging changes that increase their risk of clinical outcomes, it may be possible to design a study to measure the effect of the intervention on these outcomes directly.
...
If, however, the expected effect of the intervention is to decelerate aging changes, requiring that it must be initiated relatively early in life and sustained for decades before clinical effects occur, the logistical challenges of conducting a clinical trial long enough to detect these effects are extremely formidable.

Trialling is one very important thing, but what of the interventions themselves?

sjayo:
What I personally find fascinating is the great variation in longevity across mammals and the great variation in longevity within species such as humans. How can one mammal, with basically the same types of cells and physiology, live 77 times longer than another mammal? Discovering why this occurs seems fundamental to me.


I find it fascinating, too. But before we investigate things for being fascinating alone, how about we fix aging first? There are just waay too many fascinating things! So, how much is there in species-specific aging differences that goes beyond "being fascinating", but can actually help us to fix human aging? Let's have a look at my (student's) perspective. I might go ahead and study whales and mice and humans and might, for example, end up with a new DNA damage recognition pathway, several other tumor suppressors, countless hormonal signalling differences, and of course a respected position at a respected research institution. If I'm really lucky I'll have all that before my 50th birthday, and then I can look back and ask myself: "What did I do to fix human aging?"
I'd say, either the problem was too hard, or I tried in the wrong way.

My main way of illustrating Aubrey's point is delivery technologies: If in-situ gene therapy was working better than it does, we could start throwing bowhead genes into aged mice and see how they're doing -- great. But it seems to me that the most promising gene therapy protocols are cell-based. So, neglecting non-cell based gene therapy, slowing aging on the basis of interspecies genetic differences seems to presume that we master full body cell-based gene therapy first. But if we master it, then we will also be able to replace an organism's cells with wild-type but young ones (to be precise, wild-type here means carrying only modifications required for the replacement process itself). Thus, I would consider any non-delivery related genetic modifications for rejuvenation purposes only after the failure of the hypothesis that replacing an organsim's cells with young ones will rejuvenate it. If we're in luck, this will never happen. But even if the hypothesis fails, we will have started with creating the tools we need to implement the changes, rather than creating hypothetical changes that can perhaps never be implemented. What's your (and everyone else's) take on this one?

#75 kevin

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Posted 06 June 2005 - 05:05 AM

even if the hypothesis fails, we will have started with creating the tools we need to implement the changes, rather than creating hypothetical changes that can perhaps never be implemented


Spot on John.. focusing on goal and milestone oriented research instead of simply examining fascinating questions will cut through a lot of dilly-dallying...

#76 Mind

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Posted 16 February 2008 - 11:05 PM

Just reading through this again. A fun thing to do after a couple of years have passed. Sjayo provided a lot of good discussion points and papers (thanks much!). I am still a libertarian supporter of people who wish to experiment with newer supplements and/or hormone therapies, and I still think there is an irrational move on the part of government agencies to regulate/ban a lot of substances. Just wondering if the attitudes (or data) regarding HGH have changed much? I know many thousands of people in the U.S. use it and most claim they feel great, however, I am unaware of any recent studies that show an extension of lifespan.




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