Friday August 19 2011
The study did not investigate the effects of the drug on mice fed on a normal diet
The Daily Mail has today hailed “an all-in-one treatment that works against obesity, diabetes, heart disease and cancer”.
The news is based on lab tests of a synthetic compound called SRT1720, which was found to improve survival, motor function, insulin sensitivity and organ health in mice that were fed a high-fat diet. SRT1720 is thought to activate an enzyme that has been shown to increase lifespan in lower organisms such as worms and yeast.
Although the results of this trial show that this chemical may be of some interest, it should be noted that even if these results in mice are applicable to humans, mice fed the drug alongside a high-fat diet still had worse markers of health and reduced lifespan compared to mice on a standard diet. Also, the Daily Mail’s headline implied that SRT1720 could be used as an ingredient in a ‘red wine pill’ due to its similarity to the resveratrol compound found in red grapes. However, results on resveratrol research itself have been inconsistent.
This early-stage research in mice has very limited current implications. A cure-all pill for all cardiovascular diseases and cancers - if such a thing could ever exist - is an extremely long way off in the future.
Where did the story come from?
The study was carried out by researchers from a number of organisations, including the US National Institute on Aging, US National Institutes of Health, and Sirtris, a company owned by the GlaxoSmithKline pharmaceutical company. The research was funded by Sirtris, the National Institute on Aging and National Institutes of Health. Sirtris manufactures the SRT1720 drug tested in this research.
The study was published in the peer-reviewed scientific journal, Scientific Reports.
This story was unrealistically reported in the Daily Mail. The Daily Mail reports that the drug would allow people “to eat as much as they like without putting on a pound,” which is a puzzling claim since the mice treated with SRT1720 in this study actually put on weight while on the high-fat diet. The Mail also reported that the drug could be a treatment for diabetes, heart disease and cancer, conditions that were not investigated in the study.
It is unclear why the Mail hailed the “red wine pill” as a potential cure for “everything from obesity to cancer”. The likely reason is that the research paper says that SRT1720 has similar effect to resveratrol, a chemical found in the skin of red grapes. However, there is no consensus on whether resveratrol itself has clear benefits for health.
What kind of research was this?
This was a laboratory-based study examining a synthetic compound called SRT1720, which was identified for its ability to activate Sirt1 in mice fed a high fat diet. Sirt1 is an enzyme which has been shown to extend the lifespan in lower organisms such as worms and flies. It also improves metabolism and delays the onset of age-related diseases in mammals.
What did the research involve?
One-year-old male mice were fed either:
- a standard diet
- a high-fat diet
- a high-fat diet with a low daily dose of SRT1720 (30mg/kg bodyweight)
- a high-fat diet with a high daily dose of SRT1720 (100mg/kg bodyweight)
The researchers wanted to examine how these diets affected lifespan; fat mass; weight of the organs and their structure and function; serum levels of high-density lipoprotein, glucose and insulin; metabolism; and movement of the mice. They also monitored a variety of other measures, including motor function, insulin sensitivity, organ health and metabolic activity, as well as the genes expressed by the mice on the different diets.
The researchers then performed experiments to support their hypothesis that the SRT1720 chemical acts by activating an enzyme called Sirt1.
What were the basic results?
There were no indications that SRT1720 was toxic to the mice.
Mice on the high-fat diet had a reduced lifespan compared to mice on the standard diet. Despite the fact that all mice on the high-fat diet put on similar amounts of weight, SRT1720 treatment increased both the average and maximum lifespan of mice on the high-fat diet. Whole-body fat mass of mice on the high-fat diet was double that of mice on the standard diet. However, despite putting on equal amounts of weight, the fat masses of the mice on the high-fat diet were significantly reduced by treatment with a high dose of SRT1720.
The different diets had different effects on organ weight. The high-fat diet significantly increased the weight of the liver, heart and kidneys of the mice. Treatment with both doses of SRT1720 reduced this increase in organ weight, although the weight of the liver was still significantly greater than in mice fed the standard diet. Heart function was similar between the mice on the different diets.
However, SRT1720 reduced the accumulations of lipid (fat) droplets in the liver cells and protected against the increases in pancreas islet size experienced by mice on the high-fat diet (islet cells produce insulin, so increased size indicates increased production of insulin, which would occur if the body’s cells had developed insulin resistance).
Serum levels of high-density lipoprotein (‘good’ fat), which is positively associated with cardiovascular health, was increased in mice treated with the high dose of SRT1720 compared to all other diet groups. Circulating glucose levels were similar in all diet groups, although the insulin levels in mice fed the high-fat diet were double those of mice fed the standard diet. The high dose of SRT1720 reduced the insulin levels back to normal. Tests of insulin resistance produced similar results.
To examine metabolism, the researchers monitored the volume of oxygen consumed by the mice. This displayed the expected pattern of increased oxygen consumption during the dark period, when mice are active and feeding. Mice on the high-fat diet had increased oxygen consumption compared to mice on the standard diet. This was reversed by intake of either dose of SRT1720. Mice on the high-fat diet were less active, and this was improved by a high dose of SRT1720.
Treatment with SRT1720 caused the genes expressed in the liver to be different in mice on a high-fat diet. SRT1720 treatment suppressed genes that have previously been shown to correlate with ageing in studies on kidney and brain. SRT1720 also decreased expression of several gene sets associated with inflammatory changes.
Consistent with this hypothesis were the results of experiments that were conducted in order to examine whether SRT1720 acts by activating Sirt1.
How did the researchers interpret the results?
“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.”
In this study, a synthetic compound called SRT1720 was tested in mice fed a high-fat diet due to its ability to activate Sirt1. Sirt1 has previously been shown to extend the lifespan in lower organisms such as worms and yeast, and to improve metabolism and delay the onset of age-related diseases in mammals.
The results of this long-term mouse study support the beneficial effects of SRT1720 in mice fed a high-fat diet. Although the results of this study show this chemical may have potential, there are several considerations to be taken into account:
- This study was performed in mice. Much further study will be required before it is known whether a version of this drug will be available for human testing. Despite the promising effects of this drug, Sirtris is not putting it into clinical trials. Instead, a number of similar compounds are being developed.
- The effects of this drug were seen on mice fed a high-fat diet (16% of calories from carbohydrate, 23% from protein and 61% from fat). In this study, the researchers did not investigate the effects of the drug on mice that were fed a normal diet.
- This drug, even if a version were developed for human use, would not be an excuse for an unhealthy diet. In mice fed on the high-fat diet, even when given a high dose of SRT1720, markers of health were still worse than in mice fed on a standard diet.
- As stated above, this study had nothing to do with red wine as the Mail’s headlines imply, and it did not investigate effectiveness against the prevention of cancer.
This early stage research in mice has very limited current implications. A cure-all pill for all cardiovascular diseases and cancers - if such a thing could ever exist - is an extremely long way off in the future.