The new holy grail topics of longevity medicine are autophagy (damaged cells undergoing programmed cell death to make way for newer, healthier ones) and mitophagy (the same process for mitochondria, specifically). These two processes are largely affected by a few pathways related to macronutrient intake (where macronutrients are protein, carbohydrates, and fat).
The concept is that there is a see-saw between growth and longevity—they are opposing priorities. Growing and building muscle burns through calories, but doesn’t leave much bandwidth left over for “cleaning house” – clearing out older cells that aren’t working as well as they should, to make way for the new. Yet, this process is critical for efficient functioning for the long haul.
The three primary pathways involved in macronutrient sensing are insulin (which responds to carbohydrates, but to a lesser extent, to protein as well), mTOR (which responds to protein intake), and AMPK (which responds to calories generally). When calories, carbohydrates, and protein are high, this stimulates the growth pathway. When they’re lower, conditions favor autophagy and mitophagy, necessary for longevity.
The trick, like always, is to find the balance.
Insulin, Growth Hormone, and IGF-1
Our bodies primarily run on glucose, which can be produced most readily from carbohydrates. When we eat carbs, it becomes glucose, and higher circulating glucose triggers release of insulin from the pancreas so that the glucose can get inside cells to be used or stored for later use.
Protein can turn into glucose too, but not quite as readily. Because of this, protein can also trigger insulin release, to a lesser degree.
Our bodies are mostly made of protein, though. Because of this, protein triggers the releases of Growth Hormone, considered an anti-aging hormone by many. Growth Hormone in turn triggers release of Insulin-Like Growth Factor (IGF-1), which stimulates tissue formation with the newly ingested building blocks. It’s really IGF-1 that triggers growth.
So when you eat a meal of both carbs and protein, your body releases insulin, Growth Hormone, and (in turn) IGF-1 in order to build more of your own tissues with the food you just ingested. (Some cancers respond to IGF-1 stimulation as well, though).
Interestingly, if you fast, while insulin and IGF-1 both go down (these are the signals that actually do the building), Growth Hormone goes up… mostly because its signal is being ignored at the time. IGF-1 is low, and Growth Hormone is trying to stimulate IGF-1 release, but nobody is listening. This is why sometimes Growth Hormone and insulin work in tandem, while at other times (like in fasting) they move in opposite directions.
None of these hormones are inherently good or bad. For children, in pregnancy, or after a long wasting illness, growth is prioritized. But for those looking to optimize longevity, it’s a good idea not to overstimulate the growth pathway. When we fast, insulin and IGF-1 go down, and the body prioritizes repair and regeneration instead.
Protein, Growth, and Autophagy: mTOR
Mechanistic target of rapamycin (mTOR) is another macronutrient-sensing pathway, which responds only to protein. It was so named because a medication in testing called rapamycin suppressed it, and instead seemed to directly stimulate autophagy and mitophagy. Conversely, when mTOR is high, it stimulates growth, but is also associated with aging and development of chronic illness.
Fortunately, rapamycin isn’t the only way to lower mTOR levels. The most obvious way to do so is either fasting generally, or protein restriction specifically (one of several reasons why the carnivore diet isn’t a great long-term idea.)
It’s also possible to decrease mTOR without dietary restriction—with EGCG, an extract of green tea. Hibiscus also shows promising mTOR suppression effects, usually consumed as the primary ingredient in many fruit teas. (I tend to combine green tea with hibiscus-based fruit teas, since the flavor of green tea isn’t my favorite. Works even better, from an mTOR standpoint, during a short fast!)
Speaking of superfoods, pomegranate seems to have similar mTOR suppression effects as well.
Conserving Energy In Scarcity: AMPK
Adenosine triphosphate (ATP) is your body’s energy currency, produced by the mitochondria. The energy is stored in its three phosphate groups: when one gets broken off, energy is released, producing ADP (Adenosine diphosphate). When two get broken off, more energy is released, producing AMP (Adenosine monophosphate).
When there’s a lot of calories coming into the body in the form of macronutrients (all three of them), the mitochondria produces plenty of brand new ATP from the influx. But when there aren’t a lot of calories coming in, AMP tends to predominate over ATP.
AMP in turn activates the aptly named AMP-activated protein kinase (AMPK), which breaks down stored energy sources and turns them into new ATP sources, while also switching the body into conservation mode. This too stimulates autophagy.
Because this is its role, AMPK is low when macronutrients are freely available, and high when they are not. This is the main way to affect AMPK levels—but like mTOR, there are a few others.
The most common medication for diabetes, metformin, may affect insulin sensitivity by stimulating AMPK.
Quite a few other natural substances can likewise stimulate AMPK. These include:
- Green tea, specifically EGCG once again.
- Berberine, which also happens to have glucose effects that are quite similar to metformin
- Resveratrol – which may be part of the apparent longevity effects of moderate wine intake
Probably the best thing you can do for your longevity is occasional fasting, as calorie restriction triggers autophagy and mitophagy via all of these pathways.
Other great choices for health also include green tea intake, hibiscus, pomegranate, resveratrol, and curcumin.