Advances in Gerontology, Pt 1
By the time you read this, I will be stumbling towards my seventy-third birthday and considering whether to attend my fifty-fifth high-school reunion. Gerontology is the study of aging, so obviously, it’s an area that I’m watching like a hawk. The objective of gerontology is the squaring of the quality-of-life curve, creating greater healthspan along with the likelihood of greater lifespan. We want to be healthy until the day we die, rather than spending our final years or decades with diminished capacity for activities, significant discomfort and pain, and the likely diminution of mental capabilities. I think I’m not the only person who would rather die at 80 then live until 85, if my final five to ten years have to be spent in bed or a rocking chair, experiencing high levels of discomfort and pain and perhaps in a state of confusion and not recognizing family and friends.
While the medical and pharmaceutical-industrial complex is busily manufacturing drugs that attempt to turn back time, mother nature offers us better ways that have no danger of side effects. As the title suggests, there will be further offerings in this category.
Autophagy is the metabolic state of low energy wherein our bodies recognize a dearth of nutrition and take a pause to clean house. Autophagy is referred to as programmed cell death; the idea being that when cells become senescent, old and tired, slow moving and ponderous, it is time for them to go. For hundreds of thousands of years, autophagy functioned as God and nature intended, but in the last few generations, we have thwarted the natural order and the results have not been good.
Autophagy happens when our fuel tanks are low. When we lack direct nutrition, our bodies look to stored fat for fuel. They also turn on the autophagy switch to jettison excess baggage. When you’re on the I-10 headed west out of New Orleans and look at your car’s fuel computer and it says you can go 65 miles, as you pass the sign that says “next gas 80 miles,” and you’re on an elevated causeway with no U-turn possible, you might want to make all your passengers step out and take their luggage with them, or you’ll be walking the last fifteen miles. While that sounds rather cold in a human context, that is exactly the math your body performs when you miss a meal or two. “OK, all you cells that aren’t pulling your weight, hit the bricks!”
For millennia, autophagy functioned perfectly, because no one ate breakfast and while most ate lunch and dinner, sometimes one or both of those were skipped as well. If you had to fix three miles of sagging fence in the back pasture, you might not take a lunch break. And going back further in time, you just might not have food available every day. Before refrigeration was invented, you couldn’t just wander out of bed and go pour yourself a bowl of corn flakes or scramble up some eggs. At the very least, you had to get dressed and go milk the cow and gather up fresh eggs from the henhouse, if there were any. Today, operating under the hideous untruth invented by Harvey Kellogg that breakfast is the most important meal of the day, most of the western world is stuffing their face only minutes after rising, keeping autophagy at bay. To make matters worse, we then have a donut and coffee mid-morning, a snack in the afternoon, some cookies or a cocktail when we arrive home from work, followed shortly by dinner, and then a snack before bed and maybe even another at midnight if we wake up hungry, which is the natural state for those who ate six or more high-carb, high-sugar meals and snacks during the day. Under this rubric, autophagy virtually never happens, and your body lets a few million cells that have become toxic, dead weight ride along.
The natural way to increase autophagy, with a likely increase in healthspan, is time-restricted eating, often referred to as intermittent fasting. By letting your fuel tank run dry each day, going 16 hours or more between dinner and your first meal of the next day, the autophagy switch gets turned to the on position. It does this by switching off an enzymatic cofactor, a hormone called mTOR, a fairly recent discovery and something which shares with insulin-like growth factor (IGF) and human growth hormone (HGH) the task of switching on your anabolic metabolism. High levels of mTOR, IGF, and HGH are the holy grail of body builders, but there is a catch. Prolonged anabolism generates something called mTOR syndrome, a condition marked by reduced vitality and health, although having no significant symptoms that show up in the short term.
Every single function within the human body is designed to be cyclic. Your heart contracts and relaxes, as do the muscles of your diaphragm. Various hormones and neurotransmitters cycle with your circadian rhythm. Even the most mission-critical reactions and functions pulse. Having consistently elevated levels of anabolic hormones is a pathway to cancer as well as obesity. We may want to be anabolic during and immediately after a workout, but we don’t want that condition to be constant. Fasting, and the longer the better, switches mTOR off, and autophagy on. There is also significant evidence showing that cycling into autophagy for workouts has significant benefits for strength training.
The discovery, as well as the naming, of mTOR is interesting, at least to a geek like me. Just as the pharmaceutical industry is constantly testing chemical compounds in hopes of finding a new and profitable drug, medical researchers also comb the earth, looking for natural substances that might become the next penicillin. In 1972, a research team visited Easter Island or Rapa Nui, as it is known to the natives, and found an organism that resembled streptomyces, and which had anti-bacterial and anti-fungal properties. It is called Sirolimus in some of the literature, but the researchers initially named it Rapamycin, honoring the name of the island.
The research labs then stumbled onto the realization that rapamycin was an immunosuppressant, leading to its use in organ transplant patients. In digging to find the mechanism of action (MoA) of rapamycin, mTOR was discovered. The abbreviation stands for mechanistic target of rapamycin; rapamycin switches off mTOR. In the intervening years, mTOR’s function of turning off the autophagy switch was noted and gerontological researchers began looking at rapamycin as a potential tool for increasing autophagy. While the research is in its nascent stages, and surely there is more to be discovered, rapamycin is a natural substance, like so many herbal remedies and nutraceuticals, and so there is virtually no danger of significant or lasting adverse effects.
While rapamycin is used medically as a daily immunosuppressant, and therefore likely contraindicated in anyone with autoimmune issues, it has been shown to enhance autophagy in healthy folks when taken periodically. Existing studies have shown remarkable benefits from a weekly dose, but further study may point to a different optimal period. And while suppressing anabolism, along with promoting autophagy, is a significant boon to older folks, it should probably, based on current knowledge, not be given to anyone during growth years, and obviously not to expectant mothers. This anti-aging strategy might be best for those at least thirty years old.
As a drug needed by those with transplanted organs, Big Pharma has seen fit to charge outrageous prices for rapamycin, making it cost prohibitive for the many retired folks on fixed income, as well as a large percentage of the population who can’t afford a Ferrari. Additionally, few doctors will write you a prescription for this. However, a non-prescription form of rapamycin RapaPro, is now available from Anti-Aging Systems. Unlike pharmaceutical concoctions like Ozempic and Metformin, rapamycin is a natural product, with no known long-term adverse effects.
If you should decide to try RapaPro, the current recommendations based on the limited research we have is 5 mg taken once a week. My personal choice is to take it once a week for a period of months, and then not take it for several more. My thinking on this is to mimic natural cycles. During winter, food is not as readily available, so it makes sense to me to perhaps take RapaPro from October to March or April, although that’s just a wild guess. Since this is a new gambit, I expect more data to be published over the coming months and years.