Is It Really Good to Have the Sirtuin Genes Activated Full Time?

by Nils Osmar. Nov. 7, 2022. Medical Disclaimer

One question I’d like to see addressed with more research is whether it’s really beneficial to have the sirtuin genes activated full time, or whether we should cycle in between periods of activation and deactivation.

Many of the things people in our community are doing (such as fasting, taking cold showers, taking saunas, eating low protein or low leucine diets, eating plant-based diets, and taking supplements like NMN, resveratrol and fuocidan) activate the sirtuin genes by putting stress on the body.

Cold showers trick our bodies into thinking winter is here. This activates the SIRT1 gene and triggers mitochondrial biogenesis.
Saunas trick us into thinking we’re trapped in an arid desert, an equally dangerous situation.
David Sinclair pointed out in a recent interview that the reason plant-based diets switch the sirtuins on because the body has to work harder at extracting nutrients from plants than from animals, a signal that high nutrient animal-based food is not available.
Fasting, of course, ups the ante because no nutrients at all are coming in.
In all of these cases, the body senses a threat to its well-being, so goes into survival mode.
So all of these things have benefits and activate the sirtuins, because the body gets a clear message that our survival may be at stake.

But is it really wise to do these things full time?

Or might it be better, as some suspect, to cycle between periods of deprivation and periods of plenty — i.e., fasting and eating plant-based for a days, and letting AMPK, autophagy and the sirtuins kick in — then feasting for a few days, getting warm and cozy, eating ample protein, eating animal-based foods?

If there’s an overriding benefit to their being activated full-time, why does it take such extreme conditions to activate them?

Most animal studies have been either/or, rather than cycling between the two. The animals are either fed a high nutrient diet (and live shorter lives) or a lower nutrient diet (low in calories and protein) and live longer.

I’d like to see more studies in which animals are cycled between these two states, to study the effects on longevity.

Studies in which animals are subjected to time restricted eating without reducing their nutrients — and do live longer than ones which eat the same nutrients, without any fasting — suggest that doing the latter works almost as well for enhancing longevity, and does so without the down-sides of eating a low nutrient diet, i.e., more vulnerability to disease because the immune system depends on at least some periodic mTOR activation to stay strong.

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