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DBL%20Hendrix%20small.png College chemistry, 1983

Derek Lowe The 2002 Model

Dbl%20new%20portrait%20B%26W.png After 10 years of blogging. . .

Derek Lowe, an Arkansan by birth, got his BA from Hendrix College and his PhD in organic chemistry from Duke before spending time in Germany on a Humboldt Fellowship on his post-doc. He's worked for several major pharmaceutical companies since 1989 on drug discovery projects against schizophrenia, Alzheimer's, diabetes, osteoporosis and other diseases. To contact Derek email him directly: derekb.lowe@gmail.com Twitter: Dereklowe

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May 5, 2014

Young Blood

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Posted by Derek

Anti-aging studies, when they make the news, fall into three unequal categories. There's a vast pile of quackery, which mercifully isn't (for the most part) newsworthy. There are studies whose conclusions are misinterpreted by some reporters, or overblown by one party or another. And there's a small cohort of really interesting stuff.

Yesterday's news in the field very much looks like it belongs in that last set. Two papers (here and here) came out early in Science that result from long-running research programs on what happens when young mice and old mice have their circulatory systems joined together, coming from the labs of Amy Wagers and Richard Lee at Brigham and Women's Hospital in Boston, and Lee Rubin's group at Harvard. Wagers herself started on this work as a postdoc at Stanford almost fifteen years ago, and she clearly hit on a project with some real staying power. A third new paper in Nature Medicine, from Tony Wyss-Coray's group at Stanford, also bears on the same topic (see below).

The aged rodents seem to benefit from exposure to substances in the youthful blood, and one of these seems to be a protein called GDF11. Wagers and Lee had already reported that administering this protein alone can ameliorate age-related changes in rodent heart muscle, and these latest papers extend the effects to skeletal muscle (both baseline performance and recovery from injury) and to brain function (specifically olfactory sensing and processing, which mice put a lot of effort into).

So the natural thought is to give aging humans the homolog of GDF11 and see what happens, and it wouldn't surprise me if someone in Boston ponies up the money to try it. You might need a lot of protein, though, and there's no telling how often you'd need infusions of it, but to roll back aging people would presumably put up with quite a bit of inconvenience. Another approach, which is also being pursued, is the dig-into-the-biology route, in an attempt to figure out what GDF11's signaling pathways are and which ones are important for the anti-aging effects. That's when the medicinal chemists will look up from the bench, because there might be some small-molecule targets in there.

That's going to be a long process, though, most likely. GDF11 seems to have a lot of different functions. Interestingly, it's actually known as an inhibitor of neurogenesis, which might be a quick illustration of how much we don't know about it and its roles. It would seem very worthwhile to try to sort these things out, but there are a lot of worthwhile biochemical pathways whose sorting-out is taking a while.

The Wyss-Coray paper goes in the other direction, though. Building on earlier work of their own, they've seen beneficial effects on the hippocampus of older mice after the circulatory connection with younger animals, but were able to reproduce a fair amount of that by just injecting younger blood plasma itself. This makes you wonder if the "teenage transfusion" route might a much more simple way to go - simple enough, in fact, that I'm willing to put down money on the possibility of some experimentally-minded older types trying it out on their own very shortly. Wyss-Coray is apparently planning a clinical trial as we speak, having formed a company called Alkahest for just that purpose. Since blood plasma is given uncounted thousands of times a day in every medical center in the country, this route should have a pretty easy time of it from the FDA. But I'd guess that Alkahest is still going to have to identify specific aging-related disease states for its trials, because aging, just by itself, has no regulatory framework for treatment, since it's not considered a disease per se. The FDA has consistently avoided going into making-normal-people-better territory, not that I can blame them, but they may not be able to dodge the question forever. At least, I hope they won't be able to. You also have to wonder what something like this would do to the current model of blood donation and banking, if it turns out that plasma from an 18-year-old is worth a great deal more than plasma from a fifty-year-old. I hope that the folks at the Red Cross are keeping up with the literature.

Irreverent aside: (Countess Báthory, an apparent pioneer in this field whose dosing protocols were suboptimal, does not seem to be cited in any of the press reports I've seen. Not sure about her publication record, though - maybe she's hard to reference from the primary literature.

Comments (14) + TrackBacks (0) | Category: Aging and Lifespan | Biological News


COMMENTS

1. PPedroso on May 5, 2014 8:29 AM writes...

Loved the irreverent post-scriptum!

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2. anon the II on May 5, 2014 9:16 AM writes...

Finally, a reason to be happy about getting old.

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3. a. nonymaus on May 5, 2014 9:21 AM writes...

I wonder if GDF11 also promotes tumor growth?

On the other hand, I think there was a long-running clinical trial of this that was being done in Transylvania and London, although n was too small to draw conclusions.

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4. a. nonymaus on May 5, 2014 9:23 AM writes...

I wonder if GDF11 also promotes tumor growth?

On the other hand, I think there was a long-running clinical trial of this that was being done in Transylvania and London, although n was too small to draw conclusions.

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5. PPedroso on May 5, 2014 9:37 AM writes...

Alkahest should hire Mick Jagger as consultant.

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6. newnickname on May 5, 2014 10:04 AM writes...

Sub-optimal or not, the Countess's prior work could undermine potential patent claims. On the other hand, since she never made a voluntary public disclosure, could the testimony of others be regarded as unauthorized disclosures of trade secrets?

According to wiki, GDF11 is also known as Bone Morphogenic Protein 11 (BMP-11). I know that Boston's own Genetics Institute studied BMPs for decades but I don't know which ones. Did GI ever do anything in the anti-aging field?

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7. cyn on May 5, 2014 10:17 AM writes...

I wonder how long it will take until interns will be screened based on the compatibility of their blood type with that of the upper management...

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8. sue on May 5, 2014 10:48 AM writes...

Do you hear that? It's the sound of a thousand amateur authors beginning their modern vampire novels.

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9. Barry on May 5, 2014 11:27 AM writes...

"...Alkahest is still going to have to identify specific aging-related disease states for its trials, because aging, just by itself, has no regulatory framework for treatment, since it's not considered a disease per se..." And no insurer will reimburse treatment for what's not defined as a disease.
Sure, there are a few rich codgers who'll try this out of pocket. But no one will put up the money for a clinical study unless there's a patentable therapy for a disease at the end of it.

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10. In Vivo Veritas on May 5, 2014 11:46 AM writes...

Finally, a use for all of that banked cord-blood!
Can't wait for the marketing around that one. The bankers will even know the Moms exact age. I suspect the soft-sell will start at ~45. By 50 it will be the full assault - "become your younger self".
Damn, I'm in the wrong field. :)

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11. Curt F. on May 5, 2014 1:01 PM writes...

The name Alkahest is...interesting. Alchemists held alkahest to a be a universal solvent, even able to dissolve gold. So the idea now is that the blood of young humans is a universal solvent, somewhat similar to the nitric / hydrofluoric / sulfuric acid mixture that got mentioned here the other day? The vampire novels are kind of writing themselves.

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12. anonymoustache on May 6, 2014 12:24 PM writes...

Bathory's bathing in blood for eternal youth, and Dracula's drinking blood for immortality, are close but no cigar. It's Robert A. Heinlein that hits the bull's-eye: his Lazarus Long novels feature immortality by a periodic "rejuvenation" process, which "consists largely in replacing the entire blood tissue in an old person with new, young blood." (quoted from Methulselah's Children, p. 266 of my 1986 Baen paperback edition)

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13. inchoate on May 6, 2014 2:47 PM writes...

Beyond vampire novels, this sounds like the kind of reasearch that gets picked up by the "stem cell clinics" in eastern europe and then creates a whole lot of misery and abuse...

Anyhow, i vaguely remember that Wagers lab had a figure duplication/fabrication problem in a paper recently (for which a confused post-doc was said to be responsible). It's not that this misstep should damn their research forever -- but it doesn't make me confident in GDF11.

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14. Anonymous on May 7, 2014 1:23 PM writes...

Used to be in general press, Voodoo science now it is in "Science" magazine.

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