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How the world got lost on
the road to an anti-aging pill
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August 19, 2011: by Bill Sardi
Sirtris’ re-emergence with its Sirtuin1-gene activating SRT1720 drug gains the attention of the pharma world and health seekers. Most striking was that high-fat-fed mice did not gain weight, something that was only demonstrated in rodents with a supra-high dose of resveratrol (21,000 mg human equivalent dose). However, to produce this effect and overcome fatty liver SRT1720 had to be given in a 100 mg/kilogram dose, equivalent in human terms to 7000 mg for a 160-lb human. I’m not sure healthy humans are going to want to take seven 1000 mg pills a day, and at what cost? Lower dose (2100 mg human equivalent dose) SRT1720 produced a much more tempered effect and a modest improvement in life span. So maybe humans who are killing themselves by eating high-fat diets would benefit from this drug, but maybe not healthy people. Recognize the lab mice in this experiment were fed a 60% fat-calorie diet whereas humans generally consume 20-25% fat calorie diets. As a scientific achievement, SRT1720 is notable, but it doesn’t yet translate into a practical or affordable medicine for humans. The claim was these so-called new chemical entities under development by Sirtris were 1000-fold more powerful than resveratrol, but the dose required to produce a 44% increase in life span (about what a limited calorie diet achieves) is still quite high. And while there were no signficant side effects, this was true for mega-dose resveratrol in animal models of treatment for multiple myeloma (bone marrow cancer), but when 5000 mg of resveratrol was given to humans with this type of cancer it rapidly induced kidney failure. Bottom line, SRT1720 is a scientific achievement that is a long way from becoming an anti-aging drug. – Bill Sardi, ResveratrolNews.com
Journal name:Scientific Reports Volume:1,Article number:70 DOI:doi:10.1038/srep00070 Published18 August 2011
Full report: http://www.nature.com/srep/2011/110818/srep00070/full/srep00070.html
Sirt1 is an NAD+-dependent deacetylase that extends lifespan in lower organisms and improves metabolism and delays the onset of age-related diseases in mammals. Here we show that SRT1720, a synthetic compound that was identified for its ability to activate Sirt1 in vitro, extends both mean and maximum lifespan of adult mice fed a high-fat diet. This lifespan extension is accompanied by health benefits including reduced liver steatosis, increased insulin sensitivity, enhanced locomotor activity and normalization of gene expression profiles and markers of inflammation and apoptosis, all in the absence of any observable toxicity. Using a conditional SIRT1 knockout mouse and specific gene knockdowns we show SRT1720 affects mitochondrial respiration in a Sirt1- and PGC-1α-dependent manner. These findings indicate that SRT1720 has long-term benefits and demonstrate for the first time the feasibility of designing novel molecules that are safe and effective in promoting longevity and preventing multiple age-related diseases in mammals.