Methionine Restriction Greatly Reduces Measures of Cognitive Decline in Mice

Researchers here applied three months of a methionine restricted diet to old mice, and found that it greatly reduced age-related cognitive decline, as measured in maze tests. The methionine restricted animals perform more like young animals than like their unrestricted peers. Methionine is an essential amino acid essential to all protein synthesis. Methionine sensing is one of the more important triggers by which the beneficial response to calorie restriction is activated. Near every aspect of metabolism shifts into a more healthy, life-span-prolonging mode of operation. A methionine restricted diet thus mimics a sizable fraction of calorie restriction without eating less. The methionine restricted mice actually ate more food than their unrestricted counterparts, while having a lower body weight.

Methionine restriction (MR) extends lifespan and delays the onset of aging-associated pathologies. However, the effect of MR on age-related cognitive decline remains unclear. Here, we find that a 3-month MR ameliorates working memory, short-term memory, and spatial memory in 15-month-old and 18-month-old mice by preserving synaptic ultrastructure, increasing mitochondrial biogenesis, and reducing the brain malondialdehyde (MDA) level in aged mice hippocampi.

Transcriptome data suggest that the receptor of fibroblast growth factor 21 (FGF21)-related gene expressions were altered in the hippocampi of MR-treated aged mice. MR increased FGF21 expression in serum, liver, and brain. Integrative modelling reveals strong correlations among behavioral performance, MR altered nervous structure-related genes, and circulating FGF21 levels.

Recombinant FGF21 treatment in cell culture balanced the cellular redox status, prevented mitochondrial structure damages, and upregulated antioxidant enzymes HO-1 and NQO1 expression by transcriptional activation of Nrf2. Moreover, knockdown of Fgf21 by injection of adeno-associated virus abolished the neuroprotective effects of MR in aged mice.

In conclusion, the MR exhibited the protective effects against age-related behavioral disorders, which could be partly explained by activating circulating FGF21 and promoting mitochondrial biogenesis, and consequently suppressing the neuroinflammation and oxidative damages. These results demonstrate that FGF21 can be used as a potential nutritional factor in dietary restriction-based strategies for improving cognition associated with neurodegeneration disorders.

Link: https://doi.org/10.1016/j.redox.2021.101940

Comments

So, a quick Google read says that 15 mg/kg is what people need as part of a normal diet. What level should be achieved in order to match the Rodent study?

Far as I can tell, the list of foods that are high or low in methionine is kind of a random, unintuitive distribution. So this could be a low willpower diet. Or not. Knowing that nothing good in this world comes without pain, especially where the body is concerned, there would probably be some subtle and maddening sensation of hunger you couldn't shake, even if you stuffed yourself.

Posted by: Paul at April 6th, 2021 9:18 AM

The question is how much of this could translate to humans. CR seems to give just a few extra years all things considered. A diet restricting M might be much less effective than CR , so we are looking at a few extra months. On the other hand, it might be very helpful for dementia or AD. Needs more studies though

Posted by: Cuberat at April 6th, 2021 1:57 PM

Answering my own question, the article I read said the diet was for about 200mg. I don't think it mentioned body weight. But I am seeing very different numbers for methionine quantities in foods. The FDA numbers were for about 150 to 200 for an egg, and other places were saying a full gram was in an egg.

Either way, I suppose, eggs are out, and all meat. Potatoes were OK and so were a lot of fruits. But it looks like a low-calorie vegan diet, more or less.

The results from this study here are nice, though. It is not life span you're trying to get out of this so much as a short to medium term improvement to health. Might be worth a go from time to time.

Posted by: Paul at April 6th, 2021 11:32 PM

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