cron-web.org

[A1CR]

[posted on behalf of CRON4heathyfuture]

Good Article in "The Scientist" magazine: Longevity in a pill; METFORMIN?

Olshansky, Spindler, some of the heavyweights are in here.

I like the emphasis on the "low-tech" metformin. Generic drug, somebody needs to champion it, it probably works.

I wonder why that Barzilai is so pessimistic?

http://www.aecom.yu.edu/endocrine/ebiobarzilai.htm

I can't touch him, he's obviously done more good than I probably ever will, but still, metformin pushes "all the right buttons". If you spend enough time with the literature, that conclusion is unavoidable.

Pumps AMPK, supplants insulin. It even freaks out your mitochondria in just the right way.

Of course, the medicolegal "controversy" regarding metformin use is something that will make it tough to implement. But I got a newsflash: the moment the doc picks up the prescription pad, you are at the craps table of biochemistry. No matter how much data is out there, there are always those "uncharacterized" post-marketing adverse effects that get quietly swept under the carpet until somebody starts counting the body bags. This is part of the "dance". You either play the pill game or you don't.

But, maybe the longevity-promoting characteristics of metformin can be emphasized in future iterations of the pharmacotherapy of aging. However, lactic acidosis is potentially a sign of mitochondrial perturbation, and that may be an unavoidable "feature" of the longevity phenotype.

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http://www.the-scientist.com/article/display/23191/

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"Stephen Spindler, professor of biochemistry at the University of California, San Diego, has shown that metformin out-performs short-term calorie restriction in inducing the gene-expression changes associated with long-term calorie restriction."

[MR]

CRON4healthyfuture wrote:

> [Good Article in "The Scientist" magazine:]
> http://www.the-scientist.com/article/display/23191/

This link likely works better:
http://www.the-scientist.com/2006/3/1/28/1/

> Olshansky, Spindler, some of the heavyweights are in here.
>
> I like the emphasis on the "low-tech" metformin. Generic drug, somebody needs to champion it, it probably works.

I initially thought that this meant that Olshansky was actually
expressing optimism about metformin -- but that sidebar is by another
author.

Actually, the issue is an anti-aging special:
http://www.the-scientist.com/toc/2006/3/

... including this piece on Aubrey de Grey and the Mprize:


http://www.the-scientist.com/blog/display/23217/
>
> I wonder why that Barzilai is so pessimistic?
>
> http://www.aecom.yu.edu/endocrine/ebiobarzilai.htm

Actually, what's surprising about the article is the OPTIMISM -- of
Olshansky, as cosigner. "We contend that conditions are ripe today for
the aggressive pursuit of the Longevity Dividend by seeking the
technical means to intervene in the biological processes of aging in our
species, and by ensuring that the resulting interventions become widely
available." Also, a debunking of the common canard that anti-aging
interventions would cost the economy or leave the elderly in poverty as
their pensions ran out: young, healthy people of advanced chronological
age could, of course, keep working into their 120s -- or retire much
earlier, on bank interest alone even, based on a shift in the standard
logic that says something like that if you put even a few hundred $/mo
away starting in your twenties, you'd be an inflation-adjusted
millionaire at 65. Shift this to 65 and 105, the same thing applies.

this is standard now from Miller, but to have Olshanksy as a cosignatory
is refreshing (despite his constant protestations to the contrary).

> Of course, the medicolegal "controversy" regarding metformin use is something that will make it tough to implement.

What controversy?

> But I got a newsflash: the moment the doc picks up the prescription pad, you are at the craps table of biochemistry. No matter how much data is out there, there are always those "uncharacterized" post-marketing adverse effects that get quietly swept under the carpet until somebody starts counting the body bags.

True -- but it's now got a VERY long, very wide history of use in
diabetics, and now that the acidosis thing has been debunked, it does
seem v. safe. The caveat is that what's a net benefit in the diseased
could still be a net loss in the healthy -- but as there don't seem to
be ANY side effects of major concern, and since the diseased are if
anything more likely to suffer such in general, a proper longevity study
in healthy rodents combined with this would be pretty darned convincing.

[A1CR]

[posted on behalf of CRON4healthyfuture]

MR said:
>Actually, what's surprising about the article is the OPTIMISM

Heh, you shouldn't be too surprised......you hang out with de Grey too much, he makes you think that all academics live in a cave reading Gustave Flaubert and crying themselves to sleep.

de Grey better get his act in gear and make some more "feasible" and implementable recommendations, because the favorite tactic of academics is to simply co-opt your position and then tack on a real, recent methodological innovation, thereupon dubbing it their "own" position!

>What controversy?

There is a black box warning on metformin, Michael. That means real clinicians will be reticent about throwing this stuff around like candy. I know that you are smart enough to "know this", so I can only guess the above is a rhetorical question.

You live in Canada, so that may be playing into your ignorance here. You must understand that America is the pioneer in whiny lawsuits.

http://www.injuryboard.com/view.cfm/Topic=871

Americans enjoy the luxury of living on the cutting-edge of stymied medical innovation, MR!