While it is known that reduced food intake can boost health and longevity, the molecular mechanisms involved remain a mystery. In a study of fruit flies, researchers at the Max Planck Institute have now identified a protein named Sestrin that mediates the beneficial, anti-aging effects of dietary restriction.
The experts found that increasing the amount of Sestrin in fruit flies not only extended their lifespan, but also protected the flies against the unfavorable effects of a protein-rich diet. Furthermore, the researchers demonstrated that Sestrin improved the health of the flies by influencing the turnover of stem cells contained in their gut.
It has recently been discovered that the restriction of certain food components – like proteins and their amino acids – is more influential than calorie reduction in determining how the body will respond to dietary restriction. On the molecular level, one particular signaling pathway known as the TOR pathway is important for longevity.
“We wanted to know which factor is responsible for measuring nutrients in the cell, especially amino acids, and how this factor affects the TOR pathway,” explained study lead author Jiongming Lu.
“We focused on a protein called Sestrin, which was suggested to sense amino acids. However, no one has ever demonstrated the amino acid sensing function of Sestrin in a living being.”
Lu and his team analyzed Sestrin in the model organism Drosophila melanogaster, which is commonly known as fruit fly. The study revealed that the Sestrin protein plays a previously unknown role in the anti-aging effects of reduced food intake. Mutant flies without Sestrin did not reap the same benefits of dietary restriction.
“We could show that the Sestrin protein binds certain amino acids. When we inhibited this binding, the TOR signalling pathway in the flies was less active and the flies lived longer,” said Lu. “Flies with a mutated Sestrin protein unable to bind amino acids showed improved health in the presence of a protein-rich diet.”
Remarkably, when the researchers increased the amount of Sestrin protein in stem cells located in the fly gut, these flies lived about ten percent longer than control flies.
“We are curious whether the function of Sestrin in humans is similar as in flies,” said Lu. “Experiments with mice already showed that Sestrin is required for the beneficial effects of exercise on the health of the animal. A drug that increases the activity of the Sestrin protein might therefore be in future a novel approach to slow down the aging process.”
The study is published in the journal Nature Aging.