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Setting the record straight on three favorite approaches to longevity
At least three approaches to human longevity that have been discussed multiple times in this blog appear to be in trouble or the subject of controversy between groups of scientists: 1. generation and use of effective and reliable induced pluripotent stem cells, 2. human telomere extension via telomerase activators, and 3. use of resveratrol and its homologs to activate SIRT1 and therefore provide health and longevity. At best, each of these approaches faces unforeseen hurdles; at worst some of them may simply not be working out. While I have liked these approaches and written about each from a positive viewpoint, there is a problematic or controversial side to each which I will cover in three different blog entries following this one.
10. April 2010 at 20:17
Hi Vince,
Hope you are doing well…
I asked the question about Reservatrol to a co-author of an anti-aging book and got this response:
What are your thoughts on Reservatrol seeing as Glaxo has invested monstrous amount of money into clinical trials for a concentrated version? I read it can extend the life of rats by 30%?
His answer:
The so-called “life extension” was in a study where all the animals were fed high-saturated-and-trans-fat, high-sugar diets to make them obese and diabetic. Such animals, fed resveratrol at huge doses, lived 30% longer than those in the same horrendous shape NOT given the supplements. When tested in normal, healthy mice, resveratrol reduced the burden of a small number of specific health parameters, but had no benefits in extending youthful lifespan:
http://www.eurekalert.org/pub_releases/2008-07/nioa-rft062708.php
http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413108001824
This failure to extend life in the face of some gains in specific health parameters is probably a mixture of two things: a failure to protect against *real* cancer (which kills an awful lot of mice), and probably a ‘dark side’ to resveratrol and/or its possible “target” in the body, the SIRT1 protein, such as some of the effects suggested in some of my Forums post, or this one on brain health:
http://www.medicalnewstoday.com/printerfriendlynews.php?newsid=113625
http://www.cellmetabolism.org/content/article/abstract?uid=PIIS1550413108001484
Even before this study came out, there were already reasons to be skeptical of the claims for resveratrol, even in flies and worms, for reasons outlined on the Foundation’s discussion forums:
http://www.methuselahfoundation.org/forums/forumdisplay.php?f=48
16. April 2010 at 00:56
Philip Terry”
Thanks for your informed post and contribution of links. I am familiar with the Sinclair et al article Resveratrol Delays Age-Related Deterioration and Mimics Transcriptional Aspects of Dietary Restriction without Extending Life Span, and the results are indeed as you say.
I suspect the fact that normally fed mice do not live longer is probably associated with lack of SIRT1 promotion by resveratrol rather than by any side effect or cancer promotion. Have you seen my more-recent post What does resveratrol do? In it I cite two papers from scientists at Amgen and at Pfizer, both of which are icy blasts at the idea that resveratrol promotes SIRT1.
And yes, the citation SirT1 Inhibition Reduces IGF-I/IRS-2/Ras/ERK1/2 Signaling and Protects Neurons does relate to SIRT1 having both positive and negative effects in-vivo. And indeed the Methuselah Foundation forum discussions seem to be highly relevant, particularly the discussion at http://www.methuselahfoundation.org/forums/showthread.php?s=a66b850c0eed67f77697df8b437a0255&t=435
The cloud of uncertainty seems to be such that resveratrol may neither activate SIRT1 nor extend lives, not even of fruit flys. I will be watching for further developments about this.
Vince