Fast Mimicking Diet 3: The Fasting PartMarch 19, 2018Fast Mimicking Diet 3 The Fast Mimicking
References: Longo: The Longevity Diet, [Science], Science Direct
, Cell Metabolism
I like to eat. I get hungry. What is it about fasting that makes me do better? Let's review. Valter Longo found that there were two processes in yeast (very primitive organism) and mice (sophisticated mammalian organism) that respond in the same way. RAS and TOR. Those are the two pathways that appear to accelerate aging. Sugar turns on RAS-PKA and extra protein turns on TOR-6SK
Growth Hormone Pathway. If you can down regulate the RAS pathway, you increase the rate of clearing out old, dead, malfunctioning tissues and organelles. That's called autophagy. TOR is an internal monitor
of nutrient density and controller of cell growth. Can't grow if you don't have enough food. Dial TOR down
and cells stop dividing and go into hunker down mode. Alter those two pathways and presto, chango, you have gotten to the root cause of aging in humans. That discovery, that these two pathways are fundamental to all life on this planet, starting with yeast and moving all the way up to humans, is Longo's key contribution to modern understanding of aging.
Fasting turns both those pathways
in the right direction. It takes about 24 hours
to use up the glucose in your liver, stored as glycogen. The human body then switches to burning fat from stores in fat cells. The brain and body utilize ketone bodies in a process termed ketolysis, in which acetoacetic acid and 3-β-hydroxybutyrate are converted into acetoacetyl-CoA and then acetyl-CoA. In yeast, glucose, acetic acid and ethanol, but not glycerol which is also generated during fasting from the breakdown of fats, accelerate aging. Not glycerol. Did you get that? There is one carbon source that doesn't turn on the nutrient recognition pathway
. Glycerol is the 3 carbon fragment that holds fats together in tri-"glycerides".
Fasting for 3 or more days in humans causes a 30% decrease
in circulating insulin and glucose, as well as a reduced level of insulin-like growth factor 1 (IGF-1), the major growth factor in mammals, which together with insulin is associated with accelerated aging and cancer. Fasting for five days results
in a 60% decrease in IGF-1and a 5-fold or higher increase in one of the main IGF-1-inhibiting proteins: IGFBP1. This effect on IGF-1is mostly due to protein restriction, and particularly to the restriction of essential amino acids, but is also supported by calorie restriction since the decrease in insulin levels during fasting promotes reduction in IGF-1. In humans, chronic fasting does not lead to a decrease in IGF-1
unless combined with protein restriction.
Did you get all that? It's the protein restriction that matters. Five days appears to be the time period in which maximum reduction of cancer growth factors and insulin occurs. You can trick the system with some glycerol which doesn't register as a sensed nutrient. And we have some markers of metabolism to show your success. 5 days. Reduced protein, animal in particular. Cut the calories down to low enough to turn on and maintain ketogenesis. Sounds like about 800 a day will work. The goal isn't to lose weight but to turn on anti-aging genes.
WWW. What will work for me. Well, I've finished one cycle for myself and lost 6 pounds while doing it and another two pounds over the subsequent three weeks. Not bad. I'm going to do two more cycles and then repeat my own lab tests. Glycerol makes an interesting little sport drink. It's slightly sweet and with a bit of flavor added from a tea, it's not so bad. I've bought some hibiscus tea.
- What nutrient can you consume that is slightly sweet and doesn't trigger calorie sensing? Answer: Glycerol
- What amino acid turns on aging, and absence turns off aging? Answer: leucine in particular.
- Five day fasting results in a 60% decrease in what? Answer: IGF-1 or our Growth Hormone surrogate marker.
- Along with that, you get up to a 5 fold INCREASE in what IGF-1 inhibitor? Answer: IGFBP1.
- What lab tests might you want to know if you were getting success in your fasting methods? Answer: Glucose, insulin, IGF-1 and IGFBP-1