There is still one point to which you did not respond. You characterized the 15% extension in EOD & resveratrol mice as "mild," despite the fact that this regimen was started in middle age.
Actually, I did address this in
my post:
The modest increase in lifespan observed in the EOD + resveratrol group is interesting, and I'd like to see it further investigated, but even that result is somewhat weakened by the fact that the controls did not reach the historical benchmark for lifespan in laboratory mice (and this strain in particular), which is ~900 d mean and ~1200 d max (10th-decile survivorship) (see again my ([references]) below for examples); this might suggest that the benefit allowed them to compensate for suboptimal husbandry conditions, but would not actually benefit animals that were better-cared-for in the first place.
To eyeball from (3), Fig. 4 [C] and [E], mean and max LS for EOD-fed, "low"-dose resveratrol were ~132 and 147 weeks, or 924 and 1029 d. That is: these animals lived about as long, on average, as the
controls of the same strain in numerous previous studies, including the adult-onset CR studies op cit -- and had a
lower maximum LS. So a claim of "extended" LS is dubious.
As a close analogy: if I ran a clinical trial of "anti-aging" drug in humans, and at the end of the trial the placebo group's mean and max LSs were 50 and 70, vs. 80 and 90 in
verum, we wouldn't hail it as a breakthrough against aging; we'd instead try to figure out what was wrong with either the controls, or the study population as a whole, and whether this meant that the drug was worthless, or protected against some disease or environmental stress, or really was an anti-aging drug that just needed to be tested in a healthier population.
This problem plagues all the claims of "extended" lifespan from non-genomic interventions other than CR, such as the "Melatonin Miracle" of the 1990s ( (1) -- gosh, from your photo, FuLL meMbeR, you might not even
remember this one! I'm an old fart!
Come on, SENS ... ). That's why the biogerontology literature keeps somberly saying stuff like “caloric restriction (CR) is the only intervention repeatedly demonstrated to retard the onset and incidence of age-related diseases, maintain function, and extend both lifespan and health span in mammals, including brain and behavioral function” (2), even tho' supplement vendors keep making contrary claims for everything from selenium to BHT.
And, of course, so far it's only one study ...
A 15% extension from two additions, that on their own, did not extend life.
To me, this outcome seems remarkable.
If it's for real, and not a statistical fluke or the result of letting the animals tolerate poor husbandry, it will be. As I said, I'd like to see further investigation.
-Michael
1. Pierpaoli W, Dall'Ara A, Pedrinis E, Regelson W.
The pineal control of aging. The effects of melatonin and pineal grafting on the survival of older mice.
Ann N Y Acad Sci. 1991;621:291-313.
PMID: 1859093 [PubMed - indexed for MEDLINE]
2. Ingram DK, Young J, Mattison JA.
Abstract
Calorie restriction in nonhuman primates: assessing effects on brain and behavioral aging.
Neuroscience. 2007 Apr 14;145(4):1359-64. Epub 2007 Jan 16. Review.
PMID: 17223278 [PubMed - indexed for MEDLINE]
3. Pearson KJ, Baur JA, Lewis KN, Peshkin L, Price NL, Labinskyy N, Swindell WR, Kamara D, Minor RK, Perez E, Jamieson HA, Zhang Y, Dunn SR, Sharma K, Pleshko N, Woollett LA, Csiszar A, Ikeno Y, Le Couteur D, Elliott PJ, Becker KG, Navas P, Ingram DK, Wolf NS, Ungvari Z, Sinclair DA, de Cabo R.
Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span.
Cell Metab. 2008 Jul 2. [Epub ahead of print]
PMID: 18599363 [PubMed - as supplied by publisher]
Edited by Michael, 09 July 2008 - 10:23 PM.
Added citation and hard numbers on LS; explicated analogy.