Intermittent fasting, also known as time restricted dieting is a good switch to turn on autophagy.
90% of people eat over a period of a 12 hour window. This is a prescription for metabolic disaster. Eating over a 4 hour window during the day a few times a week seems to work well.
Here are some notes I made of the interview. Link to video is at the bottom.
11:30 - There are 120,000 people in the U.S. that make it to age 100 but only 20 that reach age 110 (supercentenarians).
15:00 - Children of supercentenarians are 17 times more likely to reach age 100. Protections are carried in the genes. Centenarians are smaller in stature. Less growth hormone causes a reduction in mTOR. Size matters in longevity.
18:30 - Anabolistic state versus Catabolistic state. We should cycle between the two. Anabolism is improving in growth, such as muscle mass. Catabolism is breaking down, repairing, and removing. Catabolism is the phase the cell goes into when resources are scarce and the cell is looking to quit making proteins, stop cell division and instead try to find resources internally. This is called autophagy. The cell creates little garbage truck entities to find misfolded proteins, dysfunctional organelles (mitochondria) and bring these to a recycling center called the lysosome, which is basically a big bag of acid that breaks down the proteins and organelles into their component parts and releases them back into the cell. So cycling to a state of autophagy, through fasting or other means is important to create healthy proteins and mitochondria and to keep the body healthy.
23:42 - Suppressing mTOR all the time is not good. Our ancestors cycled between anabolistic and catabolistic states, driven by the change of seasons and abundance or scarcity of food. Both states are necessary and part of our evolution.
25:09 - Anabolistic state is for cell growth, including growing stem cells, which replace your muscle cells, heart tissue, cartilage, etc. All this requires that mTOR is turned on. Intentionally suppressing mTOR full time under the mistaken notion that you're suppressing cancer, creates a low population of stem cells and reduces the replacement of damaged tissues and increases loss of muscle mass. Many vegan diets can be harmful for this reason. There has to be a balance between mTOR and autophagy.
33:13 - What's the best way to get the switch between mTOR and autophagy going on and off. Intermittent fasting, also known as time restricted dieting is a good switch to turn on autophagy. Historically, there was no such thing as "breakfast" until the middle ages. The word "Breakfast" literally meant breaking your overnight fast. Cavemen turned autophagy on every night.
36:02 - 90% of people eat over a period of a 12 hour window. This is a prescription for metabolic disaster. Eating over a 4 hour window during the day a few times a week seems to work well. This mean you're fasting for 20 hours, stimulating autophagy. Other days you can eat over a 4-10 hour window. Exercising just before the 4 hour window can ramp up autophagy and give you the benefits of a 2-3 day fast.
38:36 - Many people who are old and in poor health got there because they rarely switched on autophagy. Being overweight with diabetes are symptoms.
45:48 - Cyclical time restricted eating - 2 days per week you eat within a 4-hour window, 1 day per week you eat within an 8-hour window, the other days are somewhere in between. Just before you eat, do a hard workout to ramp up autophagy.
48:00 - Although you don't want to totally suppress mTOR, you want it turned off more often than on. Clement has a diet heavy on vegetables with fish (salmon), no grains.
1:05:03 - Protocol for accurately measuring NAD levels. University of New South Wales pioneered a technique using mass spectrometry of blood and tissue. Tested blood from different age groups showing how metabolites of NAD change with age over time and how NAD plummets by the time you're 60 years old down to almost undetectable levels by the time you reach 80. NAD is essential for repairing broken DNA. Broken single strands of DNA occur about 125 times per day in every cell of your body and about 25 times per day in double stranded DNA. You need NAD in order to turn on gene repair. Lack of DNA repair as we age is a main driver of morbidity from diseases.
1:14:36 - Clement has the spectrometry machine to begin studies on how to increase NAD levels, what works and what doesn't.
1:21:44 - Ready to begin studies on liposomal NMN to see how it affects levels of NAD. Exercise and time restricted eating will increase NAMPT by 30 percent. NAMPT is the rate limiting enzyme for the recovery of NAD from nicotinamide in the salvage pathway.
1:23:48 - The technology exists to reprogram cells called CRISPR. 4 genes are responsible for reversing age, called Yamanaka factors after the Japanese scientist who discovered them. Introducing 3 of 4 Yamanaka factors into the cell over a limited amount of time will partially reverse age, resetting the methylation clock to a younger age.
1:29:41 - Will be working with Steve Horvath to see whether returning NAD levels to more youthful levels affect the methylation clock. Also determining whether senolytic interventions (quercetin and dasatanib) affect methylation clock as well.
1:35:08 - One of the causes of cellular senescence is DNA damage. Getting NAD levels back to normal is one big way to reduce cellular senescence. It's a good idea to get rid of the senescent cells before you begin taking NAD boosters.
1:38:21 - Another area they are working on is improving stem cells using CRISPR to genetically alter them and thereby reduce the risk for diseases like diabetes.
1:42:38 - Many labs today are motivated by finding a way to profit rather than necessarily finding solutions. There's not a lot of incentive for these companies to fund research for longevity on generic drugs like metformin or fisetin. They'd rather fund new synthetic drugs where the profit margin is greater.
https://www.youtube.com/watch?v=n9SQjWx ... qstuQ2HdbA
I shoot for OMAD (One Meal a Day) most days. If I slip a bit, is 20-4. Being keto adapted makes it very easy.
I am very impressed with James Clements accomplishments and knowledge on combatting aging.
He's a big believer in NAD+ therapy, and will make great strides in uncovering the best approach to restoring NAD+ levels.
Registered dietitian, Sweden.