Bad news for companies selling brain-boosting, anti-aging products: the recipe for living a long life and keeping a sharp mind might be as simple as eating less.
A recent study showed that feeding mice less food triples their lifespan and slows down the decay of several organs, particularly the brain. The research, published in the journal Nature, was carried out at the Erasmus University Medical Center and the National Institute for Public Health and the Environment (RIVM), The Netherlands.
Many studies have shown that reducing food intake increases lifespan in a wide range of animals, from flies to monkeys, but there has been little information about the effects of diet restriction on health span—the period of time that an organism is healthy, not just alive.
“Most previous studies have been preoccupied only with the impact of diet restriction on lifespan,” said George M. Martin, a pathologist at the University of Washington who was not involved in the research. According to Martin, the special merit of this study is that it looked at whether “a longer life would be one of good health.” In addition, it showed how consuming fewer calories allowed mice to live better for longer.
The scientists who conducted the research think diet restriction reduces DNA damage, which is a leading cause of aging. “The beneficial effects may have to do with the way cells’ powerhouses, the mitochondria, generate energy,” said Martijn Dollé, one of the lead authors of the study. Diet restriction may force mitochondria to be more efficient and produce fewer byproducts that could damage DNA.
The researchers investigated the effects of diet restriction on mutant mice that age rapidly due to a defect in their DNA-repair machinery. These mice are used as models for accelerated aging diseases that affect humans, like progeria. Feeding the DNA-repair-deficient mice 30% less resulted in a dramatic extension of their lifespan, up to 250%. “When translating this to children with progeria, whose average life expectancy is around 12 years, it means that they could live up to 36 years,” Dollé said. However, he pointed out, there is no guarantee that diet restriction will result in identical lifespan benefits in humans.
Also, although 30% food restriction resulted in extended lifespan, it doesn’t mean that feeding mice less than that would allow them to live even longer. “Too much food restriction will result in starvation, ultimately ending in shortened lifespan,” Dollé said.
One of the most striking findings of the study was that diet restriction delayed the aging of key organs, such as kidneys, liver, testes, and the brain, which appeared to benefit the most. When DNA-repair-deficient mice ate less, they maintained 50% more neurons than their siblings that had unlimited access to food. Diet-restricted mice also preserved all of their motor skills: for example, they were able to run, whereas siblings that were allowed to eat as much as they wanted moved slowly and often fell. According to Dollé, this finding may open new avenues for treating and preventing disorders such as Parkinson’s or Alzheimer’s.
Once the researchers knew that diet restriction helped mice live healthier for longer, they wanted to see whether it was in fact reduced DNA damage that benefitted aging.
DNA damage is almost impossible to measure directly, so the researchers took an indirect approach. Because DNA damage is a random process, mutations accumulate more often in long genes than in short ones, making long genes less likely to be expressed. Therefore, the scientists looked at how many long genes were expressed in diet-restricted versus “all-you-can-eat” mice and found that long genes were better expressed in diet-restricted mice. This suggested that they had less DNA damage.
The scientists then looked at cellular markers of DNA damage that could be seen under a microscope and observed that these were less common in diet-restricted mice than in their siblings that had unlimited food.
How diet restriction drives DNA damage reduction is still under investigation. The authors speculate that diet restriction may work as an anti-aging “remedy” by increasing natural anti-oxidant defenses and boosting cells’ metabolism.
George M. Martin and Junko Oshima, two medical doctors investigating age-related diseases, are optimistic that diet restriction could eventually help increase the lifespan of patients suffering from some premature aging syndromes. According to Martin, this study may also provide an incentive to develop drugs that “mimic the effects of diet restriction in humans.”