- Supercentenarians are the rare individuals who have made it to the age of 110 and beyond. At any given time, there are only 50 to 80 supercentenarians in the world. In the US an estimated 120,000 people make it to 100, only 20 of them make it to 110
- What sets them apart is that, up until the ages of 105 to 108, they have maintained the health of someone in their 70’s and 80’s. They have no age-related diseases, and usually die from sudden onset immune failure
- In many respects, supercentenarians age normally, while the rest of us age at an accelerated rate.
- The basis of the book, “The Switch: Ignite Your Metabolism With Intermittent Fasting, Protein Cycling, and Keto,” is essentially how to normalize your aging rate, thus allowing you to optimize your life span.
The basis of the book is essentially how to normalize your aging, thus allowing you to optimize our life span.
It is worth noting that while lifestyle plays a tremendous role, there is a strong genetic influence.
Siblings of supercentenarians have a 17X greater chance of reaching 100 anni than the rest of us, for example, and many female supercentenarians have a mutation in the IGF-1 pathway.
This makes them short in stature, so 5 ft is about the size of the normal supercentenarian woman.
In men, it tends to be a growth hormone mutation that similarly makes supercentenarian men somewhat shorter than the average man.
These mutations limit mTOR and turns on autophagy, which is what gives these people such a head-start on longevity. But there are ways for the rest of us to limit mTOR and increase autophagy too.
The Genomic Revolution with Professor George Church, PhD.
One common mistake is continuously inhibiting mTOR. It is important to cycle back and forth between inhibition and activation of mTOR. The anabolic state triggers cell growth, and that includes stem cells, the cells that can become any cell needed, anywhere in your body.
“We have a whole chapter describing the different ways that you can implement this in your own life. There is no 1 plan. There are basically guidelines. … You can still have your pizza, your cheese, cake, ice cream, et cetera, but you cannot do this day in and day out. You can’t leave mTOR on [activated] and the brakes on autophagy full-time,” says James Clement, author of “The Switch: Ignite Your Metabolism With Intermittent Fasting, Protein Cycling, and Keto,”
Meal Frequency and Timing
Based on the evidence, time-restricted feeding appears to be 1 of the essential Keys to optimal health and longevity, as there is no other way to cyclically activate and deactivate mTOR and autophagy. You have to have a period of famine, a restriction of nutrients, to enter into a catabolic state.
The Big Q: How long does this famine need to be?
To be sure, eating throughout the whole day is an Rx for metabolic disaster.
The Big A: Research by Dr, Satchinanda Panda suggests 90% of people eat across a span of 12 hrs a day, and many across even longer timespans, which clearly is not doing them any favors.
“I personally have gone now to a four-hour window,” Clement says. “I never was a big breakfast eater. I have a couple cups of coffee in the morning. But historically, breakfast didn’t exist until the Middle Ages. We didn’t evolve as cavemen eating at 6 a.m. or 7 a.m. a breakfast of eggs, toast, jam and milk.
It’s literally in the English version of the name, ‘break-fast.’ It’s the period in which you’re breaking your overnight fast. This is essential to keeping mTOR down and autophagy on as long as possible.
I would argue that people evolved to have autophagy turned on every single night of their life, not just on occasions when they once a year would go on a fast or try a ketogenic diet for a month and then go back to the normal lifestyle,” Dr. Panda says.
The sweet spot is 4-8 hrs and shrinking the eating window down to four hours a few times a week is enough.
Incorporate Exercise for Optimal Results
The timing of exercise can also play a role. If fasting for 20 hrs and eating within a 4-hr window, aggressively working out about 2 hours before breaking the fast will suppress mTOR and activate autophagy even further, increasing metabolic markers such as 5 AMP-activated protein kinase (AMPK) and decreasing insulin-like growth factor (IGF), at least in muscles.
As noted by author Clement, this strategy will actually allow 1 to achieve the benefits of a 2-3-day long fast.
“By and large, the average person, who is obese and on seven medications by the time they’re 70 years old and has hypertension and all these problems, those people got there because they weren’t paying attention to this switch,” Clement says.
“These discussions about autophagy tell people essentially what to do to turn it on, but hasn’t really focused much on the balance — the fact that we need both sides of this. I’ve also concentrated on the triggers that turn on mTOR, because if we want it on, then we want to make sure we aren’t taking supplements or doing something else that tends to inhibit it …
A branched-chain amino acid named leucine, which is four times higher in dairy than it is in human breast milk, essentially locks on mTOR … Leucine is almost like a key that, alone, without any help from anything else, in sufficient quantities, will trigger mTOR activation and turn off autophagy …
Generally speaking, if you are consuming dairy or animal meat, you will likely have sufficient levels of leucine. Now, the cell also needs, for mTOR to be working fully, insulin … which means you need certain levels of blood sugar that will essentially trigger insulin to be relatively high …
Without leucine or sufficient amino acids, mTOR is going to essentially wait. That’s what autophagy is actually meant to do — it’s to create more amino acids by breaking down organelles and misfolded proteins to supply the cell [raw material to reuse].
It’s got the sugar. It’s got the energy. The insulin receptor is turned on but it lacks the amino acids. So, through a short bout of autophagy, the cell would most likely have enough to go through with cell division or protein production.”
The Rules of Thumb
To summarize, having large amounts of dairy and/or animal proteins for 12 hrs a day or more is a Rx for metabolic disaster, as it prevents the suppression of mTOR and activation of autophagy.
One of the easiest solutions is to restrict the eating window to 4-8 hrs each day, fasting the remaining 16 to 20 hrs and, ideally, exercising a couple of hours before eating the 1st meal.
“If you look at the diets of people who don’t have the diseases of civilization, which include the centenarians in Okinawa, Greece [and] Loma Linda, California, you see that what’s really happening is that they’re running through their glycogen stores in their liver and their muscles overnight.
We only carry about 800 calories worth of energy in our glycogen stores. It doesn’t really take that much [to deplete them] … In a deficit state, insulin drops, glucagon goes up, and you enter this catabolic state. That can happen every day. I think it’s probably how humans evolved and probably we want to have happen most of the year …
This balance is what people have to find. I personally think that it’s going to be somewhere along the ratio of 8 to 4. [You could] make that eight days in a row of turning down mTOR and two days of turning it up, consecutively, or four months on of autophagy and then two months off in a repeated cycle. There are lots of different ways to do this.
In the long run, I don’t think we know what’s absolutely optimal. We just know that cycling back and forth is the way to do it. Probably, if we keep those periods relatively shorter, especially as we get older, the chance that you’re inhibiting mTOR too long goes down … On the whole, we want [mTOR] off more than we want it on, because that’s what all the long-lived people have. They all have mTOR more suppressed than normal people.”
Experiment with an cyclical time-restricted eating strategy, as follows:
- 2 days a week eat all my meals within a 4 hr window
- 1 day a week make the meal window 8 hrs
- The remaining 5 days the meal window is somewhere between 4 and 8 hrs
And daily, just before the 1st meal do a really hard blood flow restriction (BFR) training workout. The body loves variability and uses that to optimizing the whole system, avoiding anything that is too monotonous.
“I’m a big fan of walking,”author Clement says. “I go out on 4 to 8-mile walks about once a day. It’s really hard to get a power workout in a walk … But with the [BFR], it has an amazing ability to actually stress my muscles in a way that makes them grow and get stronger and larger without having to do heavy weight presses and those kinds of exercises.”
The Importance of NAD+
Overall, NAD+ may be 1 of the most important longevity molecules known. As explained by author Clement, NAD+ is a coenzyme needed by longevity-related enzymes called sirtuins. It is also required for DNA repair.
Finding data on NAD+ sorely lacking, he began his own research, starting with a clinical trial testing intravenous (IV) NAD+ in elderly people, in collaboration with Dr. John Sturges. He also underwent the treatment, which involved an infusion of 1,000 milligrams of NAD+ per day for 6 straight days, finding it remarkably effective for tremors he had had since he was 20 yrs old.
“My hands would shake … It was just some neurological problem. It wasn’t the onset of Parkinson’s at 20 years old or anything else that anyone could point to. But surprisingly, within an hour or two of starting the IV infusion, my tremors went away completely, which I had had for the previous 40 years.
I noticed later that evening that I fell asleep and didn’t wake up during the middle of the night … I woke up way earlier than I normally would, completely refreshed and ready to get back to work. This was the same kind of experiences all of our elderly patients were telling us as well. We had several people who had tremors that went away.
I think [1,000 mg of NAD+] is too much for people who don’t have issues that would cause incredibly severe NAD+ depletion … Your body uses copious amounts of NAD+ to detoxify alcohol, for example. In and of itself, drinking every single night of your life will drastically deplete your NAD+ levels.
There are other things that people do that can deplete their NAD+ levels. We’ve seen that in teenagers who get an infection, influenza or something and then all of a sudden start getting migraines.
NAD+ will totally prevent the onset of migraines for periods of two or three months at a time. People who have had multiple migraines a month who get on these iontophoresis NAD+ patches can go years without having migraines.
There are many, many symptoms of NAD+ depletion that we’re just now learning. We’re finding that restoring the NAD+ to healthy levels gets rid of these symptoms almost immediately.”
NAD+ levels dive by the time we are 60 anni, and is nearly undetectable by the time we are 80. NAD+ is a crucial part of the longevity puzzle, as it is essential for repairing broken DNA, and broken DNA is not something that occurs once in a while.
Single-stranded DNA breaks occur about 125X an hr in every cell of the body, and double-stranded breaks occur about 25X per day in every cell. DNA breaks are further accelerated if exposed to high levels of electromagnetic fields, which virtually everyone in the developed world are.
“There are lots of lifestyle practices and exposures that will increase [DNA breaks] dramatically, and you need NAD+ in order to turn on gene repair,” author Clement says.
“If [NAD+] is naturally going down — by the time you’re 60 it’s maybe 50% of what it was when you were in your 20s and 30s, and then by the time you’re 70, it’s 10% and then at 80, there’s almost none — you can see how this huge build-up of damaged DNA in every cell of your body is potentially one of the driving forces of these morbidities that you see with aging, heart disease, cancer [and] Alzheimer’s …”
While IV NAD+ is available, it’s cost prohibitive at $1,000 per IV. Fortunately, there are less expensive ways to raise your NAD+.
2 precursors to NAD+ are nicotinamide riboside (NR) and nicotinamide mononucleotide (NMN), both of which are available in supplement form. NAD+ patches are also available, and all of these are far more economical than IV.
A 1,000-milligram dose of NR has been shown to 2X the NAD+ level. The problem is that for the elderly, doubling a grossly deficient level is not enough. In people with near-undetectable levels, the NAD+ levels need to be increased by 10 to 100X.
So, while taking an NR or NMN precursor for 6 months will 2X the level, it may still be depleted. Author Clement’s study revealed many older people need 4 or 5 grams a day for a period of time to restore more youthful levels, which could end up being costly at today’s price of NAD supplements.
Back to exercise and time-restricted eating, both of these strategies will increase nicotinamide phosphoribosyl transferase (NAMPT) by about 30%, and NAMPT is the rate-limiting enzyme for the recovery of NAD+ from its metabolic breakdown product, nicotinamide. In other words, implementing time-restricted eating and fasted exercise will naturally increase our NAD+ levels even without taking any NAD+ supplements
This is worth spending more time on because it has profound anti aging effects or it helps 1 particular morbidity pathology.
It was to this end that researcher Clement wrote “The Switch: Ignite Your Metabolism With Intermittent Fasting, Protein Cycling, and Keto,” which I recommend adding to your library. Reading through it, and implementing the strategies covered in this book can go a long way toward warding off age-related diseases and optimizing longevity.
Eat healthy, Be healthy, Live lively
Have a Happy New Year Week