A potential key regulator of ageing

A recent paper in Science Advances (from the prestigious stable of Science journals) reported interesting findings related to longevity.

It is well known that calorie restriction extends lifespan across a broad range of species. Using yeast, they found that the usual life extending effects of reducing calories disappeared when the essential amino acid methionine was added.

Methionine is a special amino acid in a number of ways. Firstly, along with tryptophan, it is the amino acid present at the lowest concentration in cells. Glucose restriction further lowers its concentration, such that it may become the rate limiting amino acid for protein synthesis. Additionally, it is coded for by the codon which initiates translation (ie protein synthesis). Also, it has been suggested that calorie restriction may actually function via methionine restriction given that restriction of this amino acid produces similar responses to calorie restriction (including in mammals), but this effect is not obtained when restricting other amino acids.

Given points like these and others, the authors suggest that "Methionine serves as a key control point for regulating life span in general" and "Given the importance of methionine in regulating translation and the metabolic state of the cell, the cross-talk between glucose and methionine might be a general mechanism for coordinating the nutrient status and the translation/growth of a cell with implications beyond the regulation of life span". Possible mechanisms for this include influencing the proteasome (required for autophagy) and mTOR activity.

So could human life be extended by restricting the dietary intake of methionine? This is just one paper and only involved working with yeast. Nonetheless, it is rather intriguing in that it fits in quite well with a general trend in nutritional research.

There are four ways to reduce methionine intake: reduce protein intake overall, reduce intake of animal proteins specifically (as this amino acid is found at the highest levels in aminal proteins), supplement with glycine, or reduce food intake in general.

Reduced protein. A 2019 review article - The impact of dietary protein intake on longevity and metabolic health - states that "Lifespan and metabolic health are influenced by dietary nutrients. Recent studies show that a reduced protein intake or low-protein/high-carbohydrate diet plays a critical role in longevity/metabolic health".

Reduced animal protein. A 2020 systematic review - Associations of dietary protein intake with all-cause, cardiovascular disease, and cancer mortality: A systematic review and meta-analysis of cohort studies - states that "Different protein sources rather than total protein relate to a person's death risk. Plant protein intake was associated with a reduced risk of all-cause and CVD mortality. Animal protein intake may be associated with an increased risk of CVD mortality". Additionally, the longest living populations in the world as identified by the Blue Zones project, eat a largely plant based diet.

Glycine supplementation. The paper Glycine supplementation extends lifespan of male and female mice reports that "elevated glycine led to a small (4%–6%) but statistically significant lifespan increase". So while glycine does have an effect, it appears to be very small.

Reduced food intake. Finally, another way to reduce methionine intake, is to reduce food consumption generally. Perhaps this is one component of why fasting and the Okinawan approach of only eating until you are 80% full are beneficial.

For more information, view the paper: Life span extension by glucose restriction is abrogated by methionine supplementation: Cross-talk between glucose and methionine and implication of methionine as a key regulator of life span