62 replies to this topic

[InquilineKea]

I'm not even sure if that is a bad thing. Impaired glucose tolerance means less insulin/IGF1 signalling, which translates to anti-aging effects. Sure, it means that you'll be especially vulnerable to damage from blood glucose, but that means you should just eat a diet high in monounsaturated fats (which are probably the healthiest substrate of any).

[tunt01]

I'm not even sure if that is a bad thing. Impaired glucose tolerance means less insulin/IGF1 signalling, which translates to anti-aging effects. Sure, it means that you'll be especially vulnerable to damage from blood glucose, but that means you should just eat a diet high in monounsaturated fats (which are probably the healthiest substrate of any).

 

Thanks.  I think it's an issue in terms of MCI/dementia.  I think it's not just elevated glucose (although that is a problem).  I think the reason why we see homocysteine elevated in some phenotypes of frailty is because of the behavior of the transsulfuration pathway trying to recover sulfur AAs when the body is starved of resources.  

 

 

When you say MUFAs, is that because of the postprandial glucose lowering effects or because of something related to SIRT6, etc. ?

[InquilineKea]

Hmm - interesting points about MCI/dementia. That's something that really needs to be looked into more (esp. b/c of http://news.usc.edu/...ate-alzheimers/). It's possible that the other benefits of reducing calories are so large that those already significantly decrease the risks of dementia, but it's also the case that IGF1 signalling could be important for neuroplasticity/neurogenesis, and that too much CR can result in lower learning speeds (I've asked several experts about this and none of them have much of an idea either).

 

Regarding MUFAs - it's simply that MUFAs have the least "evil" effects of all the other substrates. I've summarized the argument here (over at https://www.quora.co...tty-acids-MUFAs):

 

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What are the downsides (if any) of eating too many monounsaturated fatty acids (MUFAs)?

(basically - olive oil, nuts, and avocados are dominated by MUFAs)

I see almost nothing.. They don't increase glucose/insulin (unlike glucose), they don't seem to stimulate IGF-1/mTOR (unlike proteins) [1], they don't get easily damaged by lipid peroxidation (unlike PUFAs), and they're less prone to producing lipotoxicity than saturated fats. They're also a big part of the Mediterranean Diet, which seems to be one of the healthiest diets ever.

Also, MUFAs won't go through glycolysis, and glycolysis is a major source of reactive intracellular aldehydes. And oleic acid is a SIRT6 activator, too.

I *suppose* that you could gain weight with enough of them, but it certainly takes a lot more MUFA calories than carb-calories to achieve any weight gain.. Maybe all the beta-oxidation would cause increased flux through the TCA cycle/electron transport chain (which would create more free radicals), but I'm not sure if that's even intrinsically a bad thing, since the mitochondria can tolerate a small increase in free radical production (it will just upregulate its repair/antioxidant enzymes). See Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets as a good example.

I recently saw another paper on how fatty acids affect autophagy. Turns out that (when not too excessive), palmitic acid inhibits autophagy, while oleic acid (a MUFA) increases autophagy. Increased autophagy is generally associated with calorie restriction.

[1] it's still possible that they could stimulate mTOR, but I wouldn't know of a mechanism yet, asides from perhaps increasing a cell's ATP/AMP ratio (and decreasing AMPK signalling through that). Even then, the activation would be much less than the direct activation of insulin (from glucose) or the direct activation of IGF1 (from proteins)

 

 

 

Edited by InquilineKea, 10 April 2015 - 11:24 PM.