How Fasting Activates Your Body’s Built-In Repair System

Autophagy and Protein

Aging is the accumulation of damage.

One of the key discoveries of the last quarter century is that the foods we eat heavily influence these damage control mechanisms.

2016 Nobel Prize in Medicine for the discovery of Autophagy

What is it and how does it affect metabolism?

Autophagy stimulates the bodies garbage men and recyclers.

The word autophagy originates from the Greek words auto-meaning “self”, and phagein, meaning “to eat”. Thus, autophagy denotes “self eating”. 

In the mid 1950’s scientists observed a new specialized cellular compartment, called an organelle, containing enzymes that digest proteins, carbohydrates and lipids. This specialized compartment is referred to as a “lysosome” and functions as a workstation for degradation

of cellular constituents. Think Pac-man!

After infection, autophagy can eliminate invading intracellular bacteria and viruses. Autophagy contributes to embryo development and cell differentiation. Cells also use autophagy to eliminate damaged proteins and organelles, a quality control mechanism that is critical for counteracting the negative consequences of aging.

Disrupted autophagy has been linked to Parkinson’s disease, type 2 diabetes and other disorders that appear in the elderly. Mutations in autophagy genes can cause genetic disease. Disturbances in the autophagic machinery have also been linked to cancer. 

Just as a car needs regular replacement of oil, filters, and belts, a cell must replace its organelles regularly to maintain normal function.

Fasting and Intermittent Fasting

Scientists have found that fasting for 12+ to 24+ hours triggers autophagy, and is thought to be one of the reasons that fasting is associated with longevity. There is a large body of research that connects fasting with improved blood sugar control, reduced inflammation, weight loss, and improved brain function.

Calorie restriction (CR) with adequate nutrition is perhaps the most effective anti-aging intervention currently known. If you are interested in learning more, I would suggest the book “The Longevity Diet, by Dr. Valter Longo.  He is the director of the Longevity Institute at University of Southern California and has done extensive research on caloric restriction.

Calorie restriction extends the life span of every organism so far tested, including yeast, worms, flies, rodents, and monkeys. It also slows or even prevents age-related diseases, including dementia, diabetes, cardiovascular and coronary disease, neurodegenerative disorders, and several types of cancer.

In a 2010 study of alternate-day fasting, patients were able to lose significant fat mass with no change in lean mass. In this schedule, subjects eat on a normal schedule on feeding days; on the alternate days, they fast. Also, the researchers noted numerous metabolic benefits—such as reduced cholesterol, triglycerides, and waist circumference—along with the weight loss.

Let’s Dig a Little Deeper

I’m somewhat of a “geek” when it comes to wanting to know the “why & how” of what the body is doing.  If this is NOT you, scroll down past this section 🙂

There are three known nutrient-sensing pathways:Insulin, mTOR (mechanistic target of rapamycin), and AMPK (AMP-activated protein kinase). Extending longevity depends on decreasing growth and metabolism, which is best done by decreasing nutrient-sensing pathways by adjusting our diets.

Insulin

When insulin activates its receptor on the cell surface, it also activates the PI3K pathway, which results in protein synthesis and cell growth and division. This activation of PI3K happens simultaneously and automatically because these nutrient sensors link inextricably to growth pathways. Insulin plays a role in metabolism as well as in increasing growth, which is normally highly conducive to species survival because animals need to grow while food is available and stop growing when it is not. However, we have food available all the time.

 Insulin is like Miracle Grow for your fat cells!

In humans, high insulin levels and insulin resistance, which are common in aging, have been consistently linked to increased risk of many age-related diseases, including cancer and heart disease.

A hormone closely related to insulin that plays a role in aging is insulin-like growth factor, or IGF-1. High levels of IGF-1 promote growth.  That’s great if you are young and an athlete, not so great as we age as it can lead to cancer and heart disease.

mTOR

Mammalian (or mechanistic) target of rapamycin (mTOR) is another important cellular nutrient sensor that is sensitive to dietary proteins and amino acids.  When you eat protein, it gets broken down into its component amino acids for absorption by the intestines, and mTOR increases.  Dietary protein restriction and fasting can decrease mTOR.

Some of the benefits of protein restriction may be related to mTOR’s effect on autophagy.

The most potent stimulus to turning off autophagy (which we want) is mTOR.

AMPK

The third nutrient sensor is known as AMP-activated protein kinase (whew, big words! Simply, AMPK). It acts as a sort of reverse fuel gauge of cellular energy stores. In your car, if you have lots of energy in the form of gasoline, the gauge reads high. In your cells, if you have lots of energy in the form of ATP (adenosine triphosphate), then AMPK is low.  Low cellular energy levels raise AMPK levels. Thus, AMPK acts as a sort of cellular fuel gauge but in reverse.

Unlike insulin or mTOR, AMPK is not responsive to any specific dietary macronutrient but assesses the overall availability of cellular energy.

Substances that activate AMPK (mimicking low cellular energy stores) are known for promoting health.

 Examples include:

•   Diabetes drug metformin

•   Resveratrol from grapes and red wine

•   Epigallocatechin gallate (EGCG) from green tea and dark chocolate

•   Capsaicin from peppers

•    Curcumin from the spice turmeric

•    Garlic

•   Chinese herb Berberine.

Calorie restriction activates AMPK

AMPK enhances the uptake of glucose into muscle cells and increases the generation of mitochondria, leading to an increased capacity for fat burning, who doesn’t want that!  AND we want more mitochondria as we age.  These little guys are found in large amounts in our brain, heart and large muscles.  AND they give us energy!

 When nutrients are not available, mTOR, insulin, and IGF-1 are low, and AMPK is high. The cells have low energy and favor maintenance, repair, and survival. Health lies in the balance.

Protein

Restricting protein without lowering calories can promote health and longevity, too.  Protein restriction, which reduces IGF-1 and mTOR, might be responsible for the majority of the benefits of calorie reduction.

Lowering protein reduces IGF-1 by 25 percent, which may be a large component of “anticancer and anti-aging dietary interventions.”

Later in life these high levels of GH (growth hormone) and IGF-1 become detrimental to longevity. Studies of centenarians have revealed that less growth hormone and IGF-1 are associated with better health and longer life. Interestingly, though, GH levels are significantly elevated during fasting. Huh?

The reason GH increases during fasting is that fasting induces a state of “GH resistance.” Thus, while GH may be higher during fasting, there is actually less growth and more repair. Dietary protein increases levels of both GH and IGF-1, which may be good or bad, depending on your stage in life.

Update Your Software

As we age (especially as we pass the age of 65), too little protein can be detrimental, as we typically lose muscle over time. Of all human tissue, muscle burns the most energy.

Muscle wasting, or atrophy, can start at as early as 40 years of age. On average, people lose 10 percent of their muscle mass per decade of life after the age of 40. By the age of 80, the typical person may have lost a full 50 percent of muscle! All the more reason to incorporate strength training into a weekly exercise program.

The Institute of Medicine of the National Academy of Sciences set the Recommended Daily Allowance (RDA) for protein to be 0.8 gram per kilogram of body weight.

Protein intake is best calculated using grams per kilogram of lean body mass because fat tissue requires little to no protein for maintenance. Online body fat calculators can provide a reasonable estimate of your lean body mass using gender, weight, and waist circumference.

200 pounds x 0.75 = 150 pounds (68 kilograms) of lean mass

If that person ate 68 grams of protein per day, he would consume 1.0 gram per kilogram of lean mass.

How much protein? The answer is highly dependent on the situation. If you are trying to build muscle, as in body building, you need to eat more protein to sustain muscle growth. Pregnancy, breastfeeding, and typical growth in children are situations in which growth is normal, and more protein is required. Over the age of 65?  You need more protein.

Keep it Simple

Ok, let me give you some “to do’s” that will help with this whole complex subject.

•  Periodic fasting can have a pronounced antiaging effects through the renewal of immune system cells. Try doing a 24 hour water fast every quarter. (check with your doctor if on diabetes medication.)

•  Reduce or eliminate “refined” carbohydrates because they stimulate both insulin and mTOR, which turns off autophagy.

•  A diet with moderate protein and plant based carbohydrates would involve eating more natural fats, which are not to be feared!  Dietary fat does not stimulate insulin, mTOR, or IGF-1.

•  Try “time restricted eating” or “intermittent fasting” three to four days per week.  A 16 hour window of “no food” has been shown to increase autophagy.

•  Build some muscle so you can burn off excess sugar in the cells, increase fat burning and grow new mitochondria!

Bottom Line

We want autophagy to happen!  As we age cells can become “zombie” cells, they don’t die, but they can turn into cancerous cells.  All ancient religions used fasting for healing, drawing closer to God, and longevity.

When we are fasting those garbage men and recyclers are going into your cells and cleaning up “zombie” cells and growing new mitochondria.

If fasting seem scary, start with Intermittent fasting or Time restricted eating “windows.”

Do we really need to eat all the food that we eat?  Examine your lifestyle choices then pick one thing you can work on and “just do it!”