Autophagy and mTOR – Inducing Supplements for longevity
AUTOPHAGY AND AGING
One of the main catabolic processes of the body is called, ‘AUTOPHAGY’, which translates into self-devouring or self-eating. Autophagy is a metabolic process during which cells disassemble and remove their dysfunctional components. You’re basically recycling cellular debris and taking out the trash.
Autophagy has many longevity-boosting benefits:
1) Reduced inflammation
2) Stronger immune system
3) Suppressed cancer and tumor cells
4) Elimination of pathogens and toxins
Decreased cellular recycling and accumulation of molecular waste inside the cells are common to all aged cells. Diminishing autophagic pathways are said to play a major role in this type of aging.
Autophagy is good for longevity because you’ll be replacing old cellular material that’s causing you inflammation and oxidative stress with new and rejuvenated cells by converting the worn out cells into energy.
According to the mitochondrial theory of aging, reactive oxygen species damage mitochondria and decrease ATP production which leads to shorter life expectancy. Therefore, autophagy is a critical component to preserving mitochondrial functioning and keeping your body youthful by eliminating the accumulation of free radicals.
AUTOPHAGY AND mTOR
Autophagy is regulated through the pathways of mTOR and AMPK. They’re part of the Kinase Triad by promoting anabolism and catabolism respectfully.
mTOR inhibits the autophagy process because it supports cellular growth, whereas AMPK helps with autophagy because of nutrient deprivation. When in an energy deficit, AMPK starts to block cellular growth by suppressing the mTORC1 pathway, which makes the body Catabolize its weakest parts to keep the healthy components in check.
Although autophagy is a catabolic process that involves protein breakdown, it’s needed for muscle homeostasis (balance)! It’s going to improve your body’s ability to cope with catabolic stressors such as exercise and fasting by helping to recycle energy and promote protein sparingness. However, dysfunctional autophagy contributes to aging through sarcopenia which is muscle loss!
At the same time, excessive autophagy can also lead to catabolism of lean tissue and muscle disorders, which again can accelerate premature aging and make you more prone to other metabolic diseases!
Your entire body and all cells are made of protein, which requires the presence of anabolic precursors and building blocks. That’s why you need mTOR and amino acids for existence and DNA repair.
THE DARK SIDE OF mTOR COMPLEX
(mTOR) Mammalian target of rapamycin promotes cellular growth, which is going to build new muscle tissue a state of anabolism! However, there’s a dark side to mTOR that’s not optimal for longevity!
(mTOR) is the master anabolic regulator that organizes many other nutrient sensors, such as insulin, leptin, and insulin-like-growth-factor (IGF-1).
IGF-1 is another hormone that supports growth development, healing, muscle building, and bone strengthening, depending on what the body needs. When the pituitary gland in your brain releases human growth hormone, then the liver will produce IGF-1 and stimulates anabolism!
Too high mTOR and IGF-1 levels are associated with different types of cancers.
Inhibiting IGF-1 has extended the lifespan of mice but there are no associations with humans.
Disrupted mTORC1 directly inhibits mitochondrial respiration, whereas decreased mTOR up regulates glycolysis and autophagy.
IGF-1 TO THE RESCUE
However, as with autophagy and mTOR – too much or too little of anything is bad as having either too low or too high levels of IGF-1 increases risk of mortality. IGF-1 as well as mTOR help to deal with environmental stressors by supporting repair processes and anabolic growth!
High circulating IGF-1 levels are associated with longer telomere length, which predicts longer life!
1) IGF-1 prevents age-related cognitive decline by promoting neurogenesis in rats.
2) IGF-1 deficiencies cause sarcopenia and muscle wasting.
3) IGF-1 increases glutathione peroxidase, which is one of the main antioxidant pathways in the body.
4) IGF-1 fights autoimmune disorders and lowers inflammation by promoting anti-inflammatory T Regulatory Cells.
Although the link between mTOR mediated IGF-1 and accelerated aging is not very strong, you’d still not want to be anabolic and growing 24/7. It’s an evolutionary mismatch as no living organism in nature would get access to high amounts of growth promoting fuel all the time.
HOW TO INCREASE AUTOPHAGY
The most effective and easiest way to promote autophagy is to do intermittent fasting! This and caloric restriction are one of the few ways we know how to increase lifespan in all species!
1) You should fast for at least 16 hours every day to even enter a fasted state! To really activate autophagy you’d have to fast for longer than that but you don’t want to have too much autophagy every day! That’s why daily time-restricted feeding with 16/8, 18/6, 20/4 or one meal a day is very good for keeping cellular turnover active throughout the days!
2) Control your insulin and blood sugar levels! Carbohydrates and amino acids from protein are going to suppress autophagy directly by stimulating insulin, IGF-1, and mTOR. That’s why a high carb nor a high protein diet alone is ideal for longevity! They do help with building muscle and strength but you don’t want to be anabolic all the time! It’s a good idea to spike anabolism only during certain parts of the day and only briefly!
3) Caloric restriction and methionine restriction can promote life extension by decreasing mTOR activity! I’d say whatever the diet is the main reasons for increased lifespan have to do with being in a state of energy deprivation under which AMPK gets elevated and thus promoting autophagy to some extent! To reap the full benefits of autophagy you’d have to be strictly fasting but you can experience milder autophagy with carb restriction and protein restriction!
4) Exercise can also stimulate autophagy! However, you’d have to do it in a state of glycogen depletion wherein you’ve activated AMPK. This can be achieved through carbohydrate restriction or exercising in a fasted state! The best time to consume calories is in a post-workout setting because you’ll be tapping into autophagy during exercise and then the food you eat later will be used primarily for lean muscle growth not fat storage nor accelerated aging!
5) Have extended fasts for 3-7 days a few times per year! This is necessary for tapping into a deeper state of autophagy that helps to rejuvenate old cells and promotes longevity! These extended fasts should be coupled with periods of higher anabolism and building muscle so that you could recover from the catabolic stressors!
That’s why the idea of intermittent fasting does not equal starvation or malnourishment. Even on the daily one meal a day schedule, you’ll be eating a lot of calories. You’ll simply be doing it within a restricted time frame and because of that you reap the benefits of both muscle growth and life extension! Timing is the most critical component to manipulating the Kinase Triad.
ADD THESE FOR AUTOPHAGY ONLY WHEN YOU DON’T WANT TO ACTIVATE mTOR
There are certain autophagy boosting foods that promote longevity! They also mimic the effects of exercise and fasting!
1) Rapamycin, is an antifungal agent that inhibits mTOR. It’s also known to suppress tumor growth and increase the lifespan in mice.
2) Sulforaphane, found in green leafy vegetables and highly concentrated in broccoli sprouts and cruciferous.
3) Curcumin, induces autophagy by activating AMPK. Piperine, which is a compound found in black pepper induces autophagy and it also boosts the bioavailability of Curcumin, which makes it a double whammy!
4) Medicinal mushrooms like chaga, reishi, shitake, and lion’s mane support autophagy and fight cancers.
5) 6-Shogaol, is a compound in ginger induces autophagy by inhibiting the AKT/mTOR pathway in human non-small cell lung cancer.
6) Resveratrol, inhibits breast cancer growth and has longevity-boosting effects because it turns on the Sirt1 DNA gene associated with longevity, also turned on when fasting!
7) The compound EGCG found in green tea induces autophagy.
8) Caloric restriction mimicking ingredients like Malabar tamarind (Hydroxycitrate), Berberine, Rapamycin trigger autophagy.
9) Polyphenols regulate autophagy. Polyphenols and Flavonoids are found in dark berries, dark leafy green vegetables, and all kinds of herbs and spices!