Fountain of youth found – in mice
Mice, at least, have found a fountain of youth: a gene that extends their life expectancy. If the same discovery is made in a human gene – which is likely – men could eventually enjoy a longer life as well.
A Bar-Ilan University team led by Dr. Haim Cohen of the Goodman Faculty of Life Sciences, together with colleagues at the Hadassah University Medical Center, the Hebrew University of Jerusalem and Carnegie Mellon University in Pennsylvania, have discovered a gene that increases survival in mammals. Their study was published on Wednesday in the prestigious journal Nature.
Many recently discovered genes that affect the lifespan of laboratory animals are part of a group called sirtuins, which can be found in every species that developed over the course of evolution. They are found in both single-celled organisms, such as yeast, and complex organisms, such as humans.
The most highly researched gene in this group, SIR2 (Sirtuin 2), has been found to prolong life in yeast, worms and flies. If this gene is removed from yeast cells, the cells age faster and live a shorter life. But if a copy of the gene is transplanted into the yeast, their life expectancy increases. Similar phenomena also occur in worms and flies.
About seven decades ago, it was discovered that if the calorie intake of animals is restricted by about 30 percent, their life expectancy increases, and they live a healthier life. This treatment, it was found, delays the development of diseases connected with aging and is now the only treatment that has proven effective in prolonging life.
More in-depth studies have shown that caloric restriction activates the SIR2 gene. Its presence is critical and, without it, there is no life extension.
Since extreme diets are not practical in humans, researchers looked for substances that could activate the gene similar to the way a diet could. They discovered some activators, including resveratrol, a substance found in red wine and produced by plants in stressful situations. Scientists agree about the positive effect of resveratrol, although the degree of its influence on the SIR2 gene is controversial.
Preservation of the SIR2 family of genes throughout evolution indicates the importance of these genes in critical life processes. In each organism in which SIR2 has been found, the gene regulates lifespan, but this was not yet proven in mammals.
Last year there were many reports in scientific literature on the extent of the genes’ involvement in the lifespan.
More than 30 research groups debated the issue in the pages of the leading scientific journals Nature and Science, but no conclusion was reached.
Cohen also examined SIRT6 (gene number six from the sirtuin group) in mice using two groups. In the first group he removed SIRT6, and in the second group he created an overexpression of the gene.
“Originally in mice without the gene, researchers saw premature aging,” Cohen said.
“They suffered spinal curvature, calcium deficiency and osteoporosis, immune system problems and diabetes – well-known conditions in man.”
“We called the second group, which we created in the lab, the MOSES mice [an acronym for mice over-expressing exogenous SIRT6], and compared their lifespan to that of wildtype mice, which possess a normal amount of SIRT6,” he continued.
Cohen and his team fed the two groups a high-fat diet containing 60% more fat calories than average.
The wild mice developed the diseases associated with aging, while the MOSES mice remained healthy. MOSES bodies contained 30% less fat, about 40% fewer triglycerides (which increase cholesterol) and 30% less diabetes compared to the MOSES mice.
Additionally, wild strain female mice usually live longer than males, but in Cohen’s tests they found that with normal diets, the MOSES male mice lived 15% longer than the wild males. However, among the MOSES females, no change was recorded.
“We found that the rise in life expectancy among males is based on the calorie restriction known to us as a basic mechanism of life extension,” Cohen said. “There is overlap between these pathways, and the SIRT6 gene is involved in it.”
“Females from the very beginning have a longer life expectancy than males,” he continued. “[This is] because the basic mechanism is already active, so the engineered males just catch up to females,” Cohen concluded.
In the current study, he said, the team made a huge evolutionary leap in the transition from yeast cells to mice, becoming the first to show that the sirtuin genes regulate lifespan in mammals. The research was conducted in laboratory animals under very sterile conditions, he says, and it is not clear if this could be duplicated for humans.
However, as the human SIRT6 gene is very similar to that in mice, there is a distinct possibility that drugs designed to activate the gene could have a positive impact on treatment of agerelated diseases.
