LONGECITY

http://groups.google...02ca24?lnk=raot

Also, check out the fightaging.org write-up on SkQ1 on Jan. 16, 2009

http://fightaging.org/

Entry titled: Other Parties Interested in Targeting Mitochondria

Um, wow? My Russian pride is swelling and I'm French Canadian. That's awesome. I hope this gets replicated and verified quickly.

huh... looks like you don't have to move the mitochondrial DNA into the nucleus after all... you just have to treat the mitochondria nicely. I really didn't think MitoSENS would be the first of the seven to yield this kind of breakthrough; assuming, of course, that this all pans out and translates to humans, yada yada.

do you think it would fit in MPrize@ home?

huh... looks like you don't have to move the mitochondrial DNA into the nucleus after all... you just have to treat the mitochondria nicely. I really didn't think MitoSENS would be the first of the seven to yield this kind of breakthrough; assuming, of course, that this all pans out and translates to humans, yada yada.

I think the yadda yadda part is the important part, though. First median life span is nice and all but pretty worthless in terms of real life extension and I have a hard time finding data on maximum life span.
Secondly Russian scientists are not known for their good methodology (think melatonin, epitalon and metformin studies - all of them basically suck, because they use sick, short-lived animals)
Then there's the small, but subtle difference between our mitochondria and rodent mitochondria. We live 30 times their life spans and are by far the longest lived primate and thus our mitochondria are probably incredibly more efficient than most other mammal mitochondria.

Oh surprise, surprise! Anisimov fails yet again to prove anything:

http://protein.bio.m...l/73121655.html

This guy makes me mad, someone care to drop him an e-mail? "Stop using genetic f'ck ups, how bout trying black 6 for a change?! C-5-7-B-L/6 really it's not that hard guys." I don't think I'll read the study after seeing SHR and HER-2/neu mice used again, I really don't want to waste my time...
Edited by kismet, 18 January 2009 - 12:56 AM.

I'm with kismet here. Once burned, twice shy, and with Russian anti-aging claims, ten times burned is two to the tenth times shy... Let's see it in Black 6, out of a completely independent lab. BTW, hasn't Mito-Q been around for a while? It's a cool idea. I would love to see this pan out, obviously, and these molecules look easy enough to make, so maybe Anthony could be providing them in my imaginary future. Thanks for the paper, kismet, and the reality check.

I'm with kismet too. "Double lifespan" = 19 months versus 9 months! = normal lifespan vs ridiculous lifespan.
Reminds me the pineal gland extracts. It seems that there are many bad russian anti-aging claims.
Edited by AgeVivo, 18 January 2009 - 10:13 PM.

Heh, I'm afraid when it comes to human-like aging, BL6 is quite a genetic four letter word in itself. Choosing a convincing model for human aging is not a problem that's easy to solve -- I feel the Russians are just choosing a different crappy compromise than westerners, not a much crappier one. That said, the particular "kink" in the control survival curve does look rather taylored to support a median lifespan claim. The absence of a difference in max lifespan is disappointing, and the choice of the headline does have something in common with cold war diplomacy. But so do pop science headlines describing many western lifespan experiments. Really, I don't think these guys are much worse than our own.

Heh, I'm afraid when it comes to human-like aging, BL6 is quite a genetic four letter word in itself.

I don't think rodents are the perfect modell organism in the first place (at least they're rather cheap), but I guess that isn't what you were saying. What better strains are there? Wild mice? The NIA's genetically heterogeneous lab mice?

I don't think rodents are the perfect modell organism in the first place (at least they're rather cheap), but I guess that isn't what you were saying.

Yes, that is exactly what I'm saying. There are no generally "good" models. So I think it's not right to blame the Russians specifically for choosing a poor model. So does everybody.

still, among the following 4 curves it seems that the abnormal one is the control:

and why on earth did they consider SHR (Spontaneous Hypertensive) and HER-2/neu (breast cancer) mice??? especially after seeing their good knowledge of longevity models (Podospora anserina, Ceriodaphnia affinis, fruit flies)! if they had showed a good result with BL6 i would have tried it at home; but with such results i'd guess that they tried it, had bad results and did not want to show it. what do you think?

I absolutely agree. What I'm saying is BL6 is highly abnormal too. Why specifically would you think that BL6 is in any way a better model for whatever it is that you care about than these strains?

For supplement users, it might be a very promising alternative to Ubiquinol / CoQ10 after a safety study done (mostly regarding interactions, blood clotting, behavior during hypoxia).

It just hasn't been researched whether this can reverse any damage, e.g. sufficiently bring up mitochondrial counts in
sedentary / metabolic syndrome animals, if given in the middle of life... indeed the current curves may speak against that.

All interventions like these should be tested even on 1-2 year old IGF-IR mutant mice or ICER I gamma mice without prior intervention,
which resembles the normal american population (diabetes model :/). Perhaps John or someone else with credibility
could even drop these researchers a short line and encourage them to do such research that sheds light on damage reversal
efficacy instead of only prevention. Not impossible they'd be willing to provide that research if they knew.
Edited by mixter, 21 January 2009 - 12:10 PM.

I absolutely agree. What I'm saying is BL6 is highly abnormal too. Why specifically would you think that BL6 is in any way a better model for whatever it is that you care about than these strains?

I think the argument is that BL6 generally live longer (max and average life span) than SHR mice for instance, having a longer natural life span, one could assume that their bodies have better repair mechanisms for aging damage and cope better with or develop less pathologies. If they develop pathologies and your supplement happens to treat them voilá fake life extension.
Yes, C57BL/6 is still an inbred and short-lived strain, when compared to wild mice, but as far as I know it's one of the best researched and longest-lived inbred strains.

Using wild mice or even better non-human primates would be optimal, but researchers have to make trade-offs, experiment duration and cost will rise with those species, but their aging is most probably more representative of human aging. The problem with Russian research, mostly Anisimov et al, is they never bother with any longer lived and healthier species or strains than SHR mice.

If they really believed in their Metformin research for instance, why not study Metformin in wild mice or any bigger mammal? Most often they "prove" efficacy of compounds in SHR mice and just move on to the next. Their research is one big farce. Well, maybe they don't have the money, but I don't think so...
Edited by kismet, 21 January 2009 - 02:18 PM.

I absolutely agree. What I'm saying is BL6 is highly abnormal too. Why specifically would you think that BL6 is in any way a better model for whatever it is that you care about than these strains?

They don't die early of specific pathologies; their survival curves (when properly husbanded) are nice and square; and they have about as long a lifespan as Mus musculus gets. What all of this suggests is that when you see their lifespans improved, you're not just putting off early mortality or preventing some specific disease (which is what we've been doing in humans for the last century or more), but are doing something that intervenes in the global aging of the mouse.

Additionally, C57BL/6 has a kind of "first mover advantage:" precisely because already it's been used so extensively for biogerontology studies, we know a lot about its aging process, at both the structural and functional level, as well as its lifespan, and about its responses to multiple interventions (including, of course, CR) purported to retard aging.

-Michael

If there's this much debate about methodology because they didn't choose a specific strain of mice, how are we supposed to extrapolate any of this to "a specific strain" of humans, much less all humans?

If there's this much debate about methodology because they didn't choose a specific strain of mice, how are we supposed to extrapolate any of this to "a specific strain" of humans, much less all humans?

If we start creating inbred human strains with specific genetic defects, this will be a problem. For normal human populations, we need to use a sufficiently large sample to represent normal diversity, but that's about it. Pharmacogenomics will address the problems that come up with genetic variation in, for example, drug metabolism.

This doesn't remove the known difficulties of comparing therapies, diets, etc between different species.

I imagine that the current model would work well for certain areas of Kentucky and Apppalachia
Do they do any studies on large, genetically diverse populations of mice, or is this too impractical? I apologize, clearly we have a room full of experts here with a few laymen interjecting.
Edited by PetaKiaRose, 27 January 2009 - 08:00 PM.

I imagine that the current model would work well for certain areas of Kentucky and Apppalachia
Do they do any studies on large, genetically diverse populations of mice, or is this too impractical? I apologize, clearly we have a room full of experts here with a few laymen interjecting.

I can only guess that the answer is: yes, they do, just what are the real benefits?  As obviously the mice are not as perfectly heterogenous as, say, huge human cohorts*
"UM-HET3 mice[,] the progeny of CB6F1 females and C3D2F1 males and are genetically heterogeneous, the equivalent of a large sibship" (from the mfoundation)

*could anyone tell me if I used the comma correctly? 

Heh, I'm afraid when it comes to human-like aging, BL6 is quite a genetic four letter word in itself.

...What better strains are there? Wild mice? The NIA's genetically heterogeneous lab mice?

I interjected the question in the hope someone would notice and start a debate on their (possible) advantages.

Is SkQ1 available to take in supplement form? Or is it found in anything available in nature?


Crep

There was a great article written over on Ouroboros on SkQ1 on Jan. 28

SkQ1: A mitochondrially targeted antioxidant that extends lifespan
Edited by Aphrodite, 30 January 2009 - 05:15 AM.

Good article. Didn't answer my first question though, is this skq1 commonly found in a current supplement, fruit, vegetable, etc.?

Crep

There was a great article written over on Ouroboros on SkQ1 on Jan. 28

SkQ1: A mitochondrially targeted antioxidant that extends lifespan

Do they do any studies on large, genetically diverse populations of mice, or is this too impractical?

- Intervention Testing Program = robust tests of life-extension in mice: officious page - official page
- MPrize@ home = distributed environments; to start in a few months i guess; we may all here participate

Is SkQ1 available to take in supplement form? Or is it found in anything available in nature?

What i read is that SkQ1 was built by V.P.Skulachev's team. In http://protein.bio.m...l/73121641.html ,"To the right eye, Vetomitin, a pharmaceutical form of SkQ1, was daily instilled whereas the left eye was used as a control to the SkQ1 treatment"
Don't know however for the supplement form...
Edited by AgeVivo, 31 January 2009 - 05:37 PM.

Good article. Didn't answer my first question though, is this skq1 commonly found in a current supplement, fruit, vegetable, etc.?

Crep

There was a great article written over on Ouroboros on SkQ1 on Jan. 28

SkQ1: A mitochondrially targeted antioxidant that extends lifespan

No. SKq1 (plastoquinonyl-decyl-triphenylphosphonium) is synthetic. It's action is similar and related to that of Mito-Q. Like Mito-Q more than nano-molar amounts are counterproductive. A chemist I knew synthesized Mito-Q and fed it to some pet worms he kept. They died. He had the dose wrong, or else messed up the synthesis. There are requests out in the Chinese trade-lead web sites asking for help in synthesizing plastoquinonyl-decyl-triphenylphosphonium, so we may see people selling it in a few months. I will not be among the first to try it.

their good knowledge of longevity models (Podospora anserina, Ceriodaphnia affinis, fruit flies)!

I looked at Ceriodaphnia affinis. They say

The crustacean C. affinis is a convenient subject for lifespan research since its imago life cycle is usually as short as 15-20 days and cultivation under laboratory conditions is not a problem

I googled a little. In fact Ceriodaphnia affinis is a synonym for sor Ceriodaphnia dubia, which i a much more common name. It's a sort of small/tiny schrimps that eat algua and that anyone can culture in glass bottles but the issue i see for lifespan tests (except that it is not a human ;-) is that C. dubia is extremely sensitive to toxics. In fact it is generally used to test if water is safe (if it isn't C. dubia dies).

So i wonder if sQ1 extended C dubia's life simply because sQ1's high antioxidant activity cleans the water...

Anyone in contact with Anisimov or someone else from the laboratory? To know if they tested C57BL6 or not. I mean, their reported tests are very questionable but often not everything is published and it might be informative to know more about what they did, plus a specifically mitochondrial antioxidant makes sense against aging.