As I understand fasting triggers mito fusion and the first part of the protocol also triggers fusion. What I do not get is fasting triggers autophagy and apoptosis which we achieve with the second part of the protocol. So when I hear fasting is used in the c60 study I always thought it is the second part of the protocol achieving this instead of the first part. Still quite confusing for me as I intuitively feel going into a fasting state using nicotinamide rather than stearic acid. Just trying to wrap my head around this
What fasting promotes depends on the conditions --
Here, we address these questions by examining mitochondrial morphology under nutrient deprivation. Our results demonstrate that mitochondrial elongation is induced shortly after starvation. This mitochondrial tubulation is reversible and depends on the specific nutrients depleted. Mitochondrial elongation does not occur when autophagy is induced by serum depletion or glucose elimination. Rather, mitochondrial elongation is a specific response to deprivation of glutamine and/or amino acids, with faster, more extensive mitochondrial tubulation upon additional depletion of glucose and serum. We demonstrate that starvation-induced mitochondrial elongation is mediated by down-regulation of Drp1, leading to unopposed mitochondrial fusion. The mitochondrial elongation response is further shown to protect mitochondria from autophagic turnover under starvation conditions.
https://www.ncbi.nlm...les/PMC3121813/
The following was found in humans--
Mitochondrial fusion protein (Mfn2) significantly increased in endurance-trained subjects in both fasted and high-fat diet state. Mfn2 protein content tended to be higher in the fasting state but significantly increased following the high fat meal in the endurance-trained subjects.
https://onlinelibrar...1002/jcsm.12611
So a combination of fasting, following by a high fat meal would produce the greatest fusion. If the rats in the Baati trail were fasted and then fed olive oil, that would have produced the highest level of fusion proteins. Assuming their mitochondria respond in the same way, of course.
Rats are easy to get into a fasting state as their metabolic rate is 6 times that of humans. I can't expect most people to fast for this, thus I use things like stearic acid and DHM to get fusion.
Mitochondrial fission is necessary for both mitophagy and apoptosis. This is achieved with nicotinamide in the second part of the protocol, which increases NAD+.
Nicotinamide Treatment Facilitates Mitochondrial Fission through Drp1 Activation Mediated by SIRT1-Induced Changes in Cellular Levels of cAMP and Ca 2...These results suggest that NAD+-mediated SIRT1 activation facilitates mitochondrial fission through activation of Drp1 by suppressing its phosphorylation and accelerating its dephosphorylation. https://pubmed.ncbi....h.gov/33802063/
Edited by Turnbuckle, 12 September 2022 - 09:53 PM.