Should You Restrict Protein, Carbs, and Calories, or Eat More as You Get Older? AMPK, Autophagy, and mTOR

Table of Contents

This is the fifth post in a series about slowing and reversing biological aging. The first four posts are:

Food and Aging

When you think about food, health, and aging, what probably comes to mind are ideas about fasting, caloric restriction, limiting the amount of protein you eat, and eating as few carbohydrates as possible.

These ideas about food have dominated the health space for years now, largely as a result of a focus on AMPK, autophagy, and mTOR, key processes that influence health and longevity.

AMPK, Autophagy, and mTOR

Most longevity scientists and biohacking enthusiasts place a major focus on AMPK, autophagy, and mTOR, portraying AMPK and autophagy as longevity promotors and mTOR as a longevity saboteur. But I believe that the orientation to these phenomena need to be adjusted, especially in older people. All of these processes can be considered "youth factors", but only when in balance.

AMPK stands for adenosine monophosphate kinase. It is an enzyme that adds phosphate molecules back to adenosine monophosphate (AMP) to form adenosine triphosphate (ATP), the body's main energy currency. AMP is formed when phosphate molecules are removed from ATP to release the energy stored in the bonds between phosphate and adenosine. When more phosphates are removed than are added back, ATP is said to be "depleted".

ATP depletion occurs when calorie intake is lower than calorie expenditure, such as during a fast, between meals, in a carlorie-restricted diet, or during exercise. Because AMPK's main role is responding to depletion of ATP, it is sometimes referred to as a "sensor" of energy status.

However, AMPK activation can be increased by means other than ATP depletion. Some nutrients like lipoic acid and phytonutrients like berberine, curcumin, quercetin, and EGCG (epigallocatechin gallate), and the fiber glucomannan (found in konjac root) promote AMPK in a variety of ways.

Here are the main actions of AMPK that are of interest in promoting health and longevity:

Increases autophagy (recycling damaged cells and cellular components)
Increases the burning of fat for energy
Increases glucose uptake and utlization by cells independent of insulin signaling
Reduces glycogen synthesis
Reduces the synthesis of fatty acids and cholesterol
Inhibits mTOR (mammalian/mechanistic target of rapamycyin)

mTOR is an enzyme that promotes growth processes. In recent years, there has been an almost obsessive focus in the longevity sector of the health space on AMPK activation, largely in order to inhibit mTOR and promote autophagy, and mainly through fasting and other forms of caloric restriction, as well as restriction of protein and/or carbohydrates.

mTOR Phobia

The reason that mTOR inhibition has been seen as desirable is that mTOR promotes growth processes, one of which is angiogenesis, the formation of new blood vessels. Since cancer is an out-of-control growth process, and angiogenesis supports cancer growth, mTOR has been vilified as a pro-cancer process.

This has led to what I think of as an "mTOR phobia", which causes people to fear eating and to overemphasize fasting or overly limit their consumption of protein and/or carbohydrates. But activating mTOR is not going to suddenly give you cancer because it does not actually cause cancer. mTOR would most likely only support cancer growth if it is already under way.

In fact, mTOR is essential to processes like protein synthesis for immune function, so we cannot live without sufficient mTOR activation, and you cannot kill cancer cells without a certain amount of mTOR activation to maintain immune function.

Focusing on mTOR inhibition is probably only potentially desirable when you already have cancer. But many health influencers would have you behave as if you have an undetected cancer ready to rage out of control if you eat a steak or occasionally indulge in some ice cream. This tends to feed into food phobias, disordered eating, and "orthorexia".

As discussed in my Eat4Earth interview with Linda Isaacs, MD, many people with cancer have beaten cancer while on a diet high in animal proteins or high in carbohydrates, both of which promote mTOR signaling. So mTOR inhibition may not be as important in cancer prevention or recovery as it is typically made out to be.

It is also important to realize that in older people mTOR gets harder to activate, so mTOR inhibition may be of much less value in older people than in younger people. In fact, focusing on mTOR inhibition after a certain age could potentially cause more harm than good because older people tend to lose key youth factors like immune function and muscle mass due in part to a declining ability to activate mTOR.

Autophagy Hysteria & Optimization

Autophagy (recycling of damaged cells and cellular components) has been heavily promoted along with mTOR inhibition. But what is almost never acknowledged amid the autophagia hysteria is that when ATP is overly depleted, autophagy is less activated than when ATP is less depleted, relatively speaking.

Maintaining ATP levels during fasting or caloric restriction requires the ability to oxidize long-chain fatty acids for energy, a process that requires sufficient B vitamins like biotin and riboflavin. So people with B vitamin deficiencies could potentially fail to achieve the level of autophagy they seek if their ATP levels drop too much due to B vitamin deficiencies.

Autophagy is also less active in the presence of oxidative stress. So controlling oxidative stress is important to optimizing autophagy. Many of my clients come to me with runaway oxidative stress and are therefore less able to activate autophagy until they resolve the cause of their elevated oxidatives stress. Does this mean they should starve themselves even more intensely in order to promote autophagy? Probably not!

I think that the health space needs to relax its focus on restriction of calories, carbohydrates, and protein as the means of increasing autophagy and taking into account factors like oxidative stress, the causes of oxidative stress (e.g. toxicants and infections), relative levels of ATP depletion under various conditions, and nutrient deficiencies that affect the degree of ATP depletion under various conditions.

Are AMPK Activation and mTOR Inhibition "Over-Prescribed"?

AMPK and autophagy activation and mTOR inhibition seem more relevant to young people and people experiencing health conditions brought about by excess consumption of processed food calories. This is because AMPK and autophagy activation and mTOR inhibition counteract the degenerative metabolic processes brought on by excess consumption of processed food calories.

But in healthy people eating a whole foods diet, trying to increase the activation of autophagy may not be as valuable as we have been led to believe. And surprisingly, overactivation of autophagy could increase cancer risk because established tumors use authophagy as a survival mechanism.

Plus autophagy is already happening more than we realize. Autophagy is even activated by glucose under certain conditions! (1) This is not a license to start binging on sweets, but at least some evidence suggests that popular discussions about autophagy and mTOR may not represent everything there is to know about them.

Perhaps we do not need to avoid all sugar like the plague, fast for at least 16 hours every day, chronically restrict protein and/or carbohydrates, or assume that everybody is at risk of being autophagy-deficient without these measures.

Fasting and other forms of nutrient restriction definitely have their place, especially in certain strategic interventions for various disease states, and as occasional measures in healthy people. But it seems to me that AMPK activation and mTOR inhibition may be "over-prescribed" in the health space, at least when it comes to people above an age where mTOR tends to already be inhibited and harder to activate.

AMPK, Autophagy, and mTOR in Older People

Increasing AMPK and autophagy activation and mTOR inhibition via fasting could be problematic in older people because mTOR tends to be underactivated, rather than overactivated, as we get older. This is part of the reason that lean body mass (muscles, organs, bones, and connective tissue) declines in old age, a process referred to as "sarcopenia". Underactivation of mTOR in older people also contributes to the reduced immune system function that older people tend to experience.

So further inhibition of mTOR may be counterproductive to healthspan and lifespan because lean body mass and immune system function are key youth factors. Afterall, you must have functioning organs and strong muscles to remain alive and well, and if an infection takes you out, well, you are dead. And if an infection does not take you out immediately or directly, if it becomes chronic you will still die prematurely at some point.

And when activation of AMPK and autophagy is done via fasting or caloric restriction, other things happen that are not healthy for older people. For example, cortisol is elevated during fasting and caloric restriction. But cortisol is typically already higher in older people, and elevated cortisol is another factor that promotes declining lean body mass and lower immune system function in older people.

Since exercise activates AMPK, autophagy, and mTOR, exercise should probably be the preferred way to activate AMPK and autophagy in older people, rather than fasting. And remember that AMPK is promoted by substances like lipic acid, berberine, curcumin, quercetin, EGCG, and glucomannan.

So you are not necessarily going to have too little AMPK activation or become autophagy deficient just because you're not fasting every week, or restricting your eating window to 6-8 hours every day, or limiting your protein intake to less than 20% of calories, or limiting your carbs to 50g per day, etc..

Should Older People Embrace mTOR a Little More?

So as people get older, instead of focusing so much on AMPK and autophagy activation, mTOR inhibition, fasting, caloric restriction, protein restriction, carbohydrate restriction, etc. ... the focus should probably shift toward mTOR activation instead of inhibition. Improving mTOR activation can be accomplished by increasing protein intake and assimilation, lowering cortisol, and reducing inflammation. Chronic inflammation is another factor that elevates cortisol and promotes loss of lean body mass and proper immune system function.

Overall, those of us above the age of 50 or 60, and certainly above 65, should probably ditch mTOR phobia, overthrow the obsession with AMPK and autophagy activation, and abandon the assumption that more is better when it comes to autophagy. What this means is that many older people should probably eat more protein and more calories, not less.

I'm not suggesting that you avoid AMPK activation. Just keep in mind that AMPK activation can be increased by means other than ATP depletion or restriction of protein or carbohydrates. Again, some nutrients like lipoic acid and phytonutrients like berberine, curcumin, quercetin, and EGCG (epigallocatechin gallate), and the fiber glucomannan (found in konjac root) promote AMPK. And exercise activates AMPK, autophagy, and mTOR.

A Big Challenge for Older People

The way I view the aging process, it seems to me that one of the biggest challenges facing people as they get older is being able to activate mTOR and AMPK in a balanced way. So they should be wary of the constant noise in the health space about fasting and restrition of calories, protein, and carbohydrates because it overemphasizes AMPK activation and mTOR inhibition. The body needs some signals of abundance (which promote mTOR), not just signals of adversity (which promote AMPK).

Furthermore, factors like inflammation, oxidative stress, insulin resistance, and elevated cortisol inhibit both mTOR and AMPK. So these are the big aging accelerators we must control. And these aging accelerators tend to increase as we get older but are often also at play in young people due to the challenges of modern life. Managing your aging process often comes down to finding your specific root causes of inflammation, oxidative stress, insulin resistance, and elevated cortisol (or in some cases low cortisol due to prolonged adrenal stress).

Ultimately, what is best for you depends on what state of balance or imbalance your body is in right right now, as well as your constitutional bio-individuality, which is influenced by genetics, metabolic type, and other factors. General advice to eat less and fast more could be right for some people, but quite often people need to eat more and fast less, especially if they are older and/or have already over-indulged in fasting, restriction of protein and/or carbohydrates, etc.

If you would like some help with understanding your bio-individuality, managing your youth factors, and controlling the factors that impede them, you can learn more about how I work with people by downloading the Bio-Individual Blueprint Roadmap and watching the walkthrough video.