Methionine Restriction Extends Life in Flies – Fight Aging!

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Methionine Restriction Extends Life in Flies


A sizable fraction of the benefits to health and life span resulting from the practice of calorie restriction derive from regulatory systems that are triggered by nutrient sensing mechanisms focused on specific amino acids, primarily methionine. Thus a lowered dietary methionine intake produces health benefits even when overall calorie intake remains the same. This is well demonstrated in animal models, but not well tested in humans, despite the existence of low methionine medical diets. This may be because the medical diet are expensive, and it is neither straightforward nor easy to plan and eat a low methionine diet. Guides exist, but as a practical matter it is challenging to implement.



Methionine restriction (MetR) extends lifespan in various organisms, but its mechanistic understanding remains incomplete. Whether MetR during a specific period of adulthood increases lifespan is not known. In Drosophila, MetR is reported to extend lifespan only when amino acid levels are low. Here, by using an exome-matched holidic medium, we show that decreasing Met levels to 10% extends Drosophila lifespan with or without decreasing total amino acid levels. MetR during the first four weeks of adult life only robustly extends lifespan.



MetR in young flies induces the expression of many longevity-related genes, including Methionine sulfoxide reductase A (MsrA), which reduces oxidatively-damaged Met. MsrA induction is foxo-dependent and persists for two weeks after cessation of the MetR diet. Loss of MsrA attenuates lifespan extension by early-adulthood MetR. Our study highlights the age-dependency of the organismal response to specific nutrients and suggests that nutrient restriction during a particular period of life is sufficient for healthspan extension.


Link: https://doi.org/10.1038/s41467-023-43550-2

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