5 replies to this topic

[Crepulance]

"Resveratrol shortened the lives of laboratory mice in a study published in August of 2008." Cell Metabolism 2008 August; 8(2):157-68


I don't have a username/password to cellmetabolism, but this is what Sardi said. What exactly does it say in the article. Is it true? If it is true, isn't that very very very bad for all of the people using high dose?


Crep

[kismet]

I think it's an outright lie, or maybe I can't read simple graphs? Neither low (100), standard (400) nor high dose (2400mg/kg of food) resveratrol significantly affected life span. The EOD+resveratrol group shows a slight increase. It's a study we have already discussed.

EDIT: I see what he means
"we cannot rule out the possibility that resveratrol exerted harmful effects that limited its ability to extend life span. In a small pilot study using 7.5 times our highest dose (18,000 mg/kg resveratrol in the food), five out of six mice died within 3–4 months, consistent with an earlier study of extremely high doses in rats (Crowell et al., 2004)."

Edited by kismet, 13 February 2009 - 12:12 PM.

[maxwatt]

"Resveratrol shortened the lives of laboratory mice in a study published in August of 2008." Cell Metabolism 2008 August; 8(2):157-68


I don't have a username/password to cellmetabolism, but this is what Sardi said. What exactly does it say in the article. Is it true? If it is true, isn't that very very very bad for all of the people using high dose?


Crep

You posted the entire press release before. The responses deconstructed this. An especially thought out analysis of the article, including a (then) free link to the Cell article, was part of the response HERE.

The Cell article was thoroughly discussed in a topic in these forums HERE

Resveratrol dose is a tricky thing. Different people, and different ethnic groups, will attain very different serum levels of the aglycone form in controlled studies, due to difference in enzyme phenotype. An optimum dose would be quite diferent for different people. We have seen posts discussing studies on the roll of Sirt1 on DNA repair, which may imply that an optimum dose will be higher in the aged who have suffered more damage to their gene's DNA, and will decrease with chronic use as the genes are repaired.

I think many of the high-dose users have decreased their dosage over time as the result of self-observation though we haven't taken a formal poll.

Edited by maxwatt, 13 February 2009 - 12:49 PM.

[maxwatt]

I think it's an outright lie, or maybe I can't read simple graphs? Neither low (100), standard (400) nor high dose (2400mg/kg of food) resveratrol significantly affected life span. The EOD+resveratrol group shows a slight increase. It's a study we have already discussed.

EDIT: I see what he means
"we cannot rule out the possibility that resveratrol exerted harmful effects that limited its ability to extend life span. In a small pilot study using 7.5 times our highest dose (18,000 mg/kg resveratrol in the food), five out of six mice died within 3–4 months, consistent with an earlier study of extremely high doses in rats (Crowell et al., 2004)."

Translating to human dose is not possible, but measuring core body temperature may be an indirect measure. High dose SRT1720 increased core body temperature in mice, probably by increasing the number of mitochondria in brown fat. Resveratrol increases the number and size of mitochondria, and I think in high doses also increases core body temperature. CR lowers core body temperature. There is a strong implication there is a U-shaped dose-response curve. Keeping careful records of ones waking body temperature might be one way monitor resveratrol use to stay in the sweet spot on top of the curve.

[Proconsul]

I read the August article from Cell Metabolism (Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008 Aug;8(2):157-68.) on Pubmed: http://www.ncbi.nlm....ov/sites/entrez

I think the results of the study have not been accuratedly reported. If you look at fig.4, panel E, you will find that there is a tendence for shorter lifespan for standard diet mice with both low dose and high dose resveratrol, compared with the standard diet control group. Actually the low dose group has a shorter lifespan than the high dose, but none of these differences has a statistical significance. On the other side, mice on every-other-day feeding combined with low dose resveratrol have a significantly longer life span. Here is the crucial passage:

In the context of the standard diet, resveratrol did not increase overall survival or maximum life span (Figures 4B and 4E). Importantly, the SD control group had a life span similar to that of a much larger cohort of C57BL/6NIA mice (Turturro et al., 1999). EOD feeding produced a trend toward increased longevity compared to the SD control group, but the effect did not reach statistical significance. Our results are consistent with the previous observation that the effect of EOD on longevity is diminished in older C57BL/6 mice (Goodrick et al., 1990), which is also true of DR by 40% restriction (<A onclick="toggleTabs('fullTab')" href="http://www.sciencedi...eaaa28#bbib71">Weindruch and Walford, 1982 R. Weindruch and R.L. Walford, Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence, Science 215 (1982), pp. 1415–1418. View Record in Scopus | Cited By in Scopus (196)Weindruch and Walford, 1982). Notably, EOD feeding in combination with the lower dose of resveratrol did extend both mean and maximal life span by 15% compared to SD controls (Figures 4C and 4E). We have also tested the effect of a higher dose of resveratrol beginning at 12 months of age (SDHR) on life span, and again found that longevity was not significantly affected. (Figure 4F).

Notice that the mice started their regimens at age 12 months, which correspond to about mid-life. Other studies indicate that the effect of dietary restiction on lifespan seems to decrease with the increase of the age at which it is started.

[geddarkstorm]

I read the August article from Cell Metabolism (Resveratrol delays age-related deterioration and mimics transcriptional aspects of dietary restriction without extending life span. Cell Metab. 2008 Aug;8(2):157-68.) on Pubmed: http://www.ncbi.nlm....ov/sites/entrez

I think the results of the study have not been accuratedly reported. If you look at fig.4, panel E, you will find that there is a tendence for shorter lifespan for standard diet mice with both low dose and high dose resveratrol, compared with the standard diet control group. Actually the low dose group has a shorter lifespan than the high dose, but none of these differences has a statistical significance. On the other side, mice on every-other-day feeding combined with low dose resveratrol have a significantly longer life span. Here is the crucial passage:

In the context of the standard diet, resveratrol did not increase overall survival or maximum life span (Figures 4B and 4E). Importantly, the SD control group had a life span similar to that of a much larger cohort of C57BL/6NIA mice (Turturro et al., 1999). EOD feeding produced a trend toward increased longevity compared to the SD control group, but the effect did not reach statistical significance. Our results are consistent with the previous observation that the effect of EOD on longevity is diminished in older C57BL/6 mice (Goodrick et al., 1990), which is also true of DR by 40% restriction (<A onclick="toggleTabs('fullTab')" href="http://www.sciencedi...eaaa28#bbib71">Weindruch and Walford, 1982 R. Weindruch and R.L. Walford, Dietary restriction in mice beginning at 1 year of age: effect on life-span and spontaneous cancer incidence, Science 215 (1982), pp. 1415–1418. View Record in Scopus | Cited By in Scopus (196)Weindruch and Walford, 1982). Notably, EOD feeding in combination with the lower dose of resveratrol did extend both mean and maximal life span by 15% compared to SD controls (Figures 4C and 4E). We have also tested the effect of a higher dose of resveratrol beginning at 12 months of age (SDHR) on life span, and again found that longevity was not significantly affected. (Figure 4F).

Notice that the mice started their regimens at age 12 months, which correspond to about mid-life. Other studies indicate that the effect of dietary restiction on lifespan seems to decrease with the increase of the age at which it is started.

Be careful with that figure 4. Notice how the error bars go above the mean of the non-resveratrol standard diet? The only thing one can say is resveratrol had no effect, as the changes in lifespan there are within normal variations which you will see when you sample multiple groups. Resveratrol did not decrease nor increase lifespan of those SD mice. For instance, don't ignore panel F, which shows quite nicely the survival curves. The SD resveratrol mice (even at 240mg/kg resv) had no difference in their survival curves as those on non-resv SD.

That is an interesting observation that they started at 12-14 months where CR also shows a marked decrease in effectiveness. None the less, don't forget all the other parameters that all the mice showed significant increases in such as heart and artery health, bone density and strength, and significant increases in motor coordination/control (for mice on the 30mg/kg diet). Those are all parameters which being augmented in the real world (instead of a sterile safe lab) like this could easily lead to longer relative lifespan.

It's those health increasing properties that are most interesting to me, not anything dealing with lifespan - as who wants to live longer in a decrepit body? But I'm sure there's tons of people who would love to live a normal human lifespan at full health (or closer to).

Edited by geddarkstorm, 16 February 2009 - 05:39 PM.