International Business Department           Liu Bojia           January 18, 2023

  Body-conscious people are no strangers to "calorie restriction", a popular diet that requires individuals to strictly control their daily calorie intake from food, minimising additional energy intake while maintaining the body's basic needs. Properly implemented, calorie restriction optimises metabolism and controls body weight.

  Of course, people's expectations of calorie restriction methods tend to focus on fat metabolism, unaware that calorie restriction can also slow down the rate at which you age if you're willing to stick to it. This is not the first time this conclusion has been made, scientists have found in the past that people who have been on a long-term calorie restriction regime have lower levels of aging-related DNA methylation and a younger biological age based on aging-related markers.

  A team of researchers from the Buck Institute in the United States had found several years ago that controlling the total calorie intake in bacteria could extend the lifespan of 97 per cent of strains, with 50 per cent of those strains significantly benefiting from calorie restriction. To find further mechanisms for the anti-aging effects of calorie restriction, Professor Lisa Ellerby and colleagues at the Buck Institute screened nearly 200 strains of fruit flies of different genetic backgrounds and then cultured them in groups, with one group following a regular food supply and the other enforcing strict calorie restriction.

  At the same time, they analysed genes associated with longevity in the fruit flies, and they were particularly interested in one of these genes, called mtd, because humans have a homologue of the mtd gene, OXR1, which is responsible for dealing with oxidative damage and is active in neurons, and a lack of the OXR1 protein in humans produces neurological deficits. When Drosophila perform caloric restriction, mRNA expression of the mtd gene in their brains increases sevenfold.

  If the expression of the mtd gene in Drosophila is genetically engineered to decrease, even if Drosophila enforces caloric restriction, they do not gain the benefit of life extension, suggesting that this gene is necessary to gain the life-extension benefits associated with caloric restriction.

  In their testing, the authors found that mtd/OXR1 regulates the structure of a protein called the retrograde protein transport complex (retromer), which is involved in the recycling of cellular proteins, lipids, and which determines the process by which various proteins enter neurons.

  Past studies have linked retromer dysfunction to age-related neurodegeneration, including Alzheimer's disease and Parkinson's disease. The new study confirms that this is a result of decreased mtd/OXR1 gene expression as individuals age. Calorie restriction, on the other hand, strengthens mtd/OXR1 expression for longer, enhancing the work of retromer in neurons, slowing down brain ageing and extending healthy lifespans.

  Professor Ellerby points out that when we eat less, we are actually helping our cells to distribute protein better, which is good for health. In addition to calorie restriction, the authors found that directly boosting mtd/OXR1 expression was also enough to help extend healthy lifespan, at least in Drosophila. After overexpression of Drosophila mtd, Drosophila's aging-related vision loss, Tau protein pathology traits were improved, and Drosophila lived longer.

  The team plans to confirm whether similar genetic mechanisms are also present in human samples in the future, but the benefits of calorie restriction do exist anyway: eat less and get healthier.