The Longevity Solution

by Jason Fung

  Growth hormone is the main stimulant to IGF-1. Both are highest in growing children and adolescents and decline into adulthood and old age, reflecting the different priorities of each stage of life. Childhood and early adulthood are periods in which growth is the priority, so GH and IGF-1 are high. Later in life, though, these high levels of GH 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? Why would the body increase GH when no nutrients are available? The reason GH increases during fasting is that fasting induces a state of “GH resistance.” This is caused by activation of fibroblast growth factor 21 (FGF-21), which reduces IGF-1 and increases liver expression of IGF-1 binding protein 1 to blunt GH signaling.41 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. When we are young, protein helps us mature, ensures that all systems are healthy and strong, and readies us for conceiving, bearing, and caring for children. In an adult, too much protein might promote cancer, heart disease, and other ills of aging. Considered in this new light, many of the diseases that affect adults are diseases of “too much growth.”

  For example, atherosclerosis is the underlying process of “hardening of the arteries” that causes heart attacks and strokes. Initially thought to be a disease of cholesterol blocking the arteries, it is now known to be a disease of excessive smooth muscle proliferation and inflammation that blocks the arteries. “Too much growth” in the blood vessels leads to blockages. Cancer is a disease of “too much growth” that is uncontrolled. Obesity, with its related metabolic diseases, is a disease of “too much growth.”

  Reining in this epidemic of “too much growth” depends on decreasing growth pathways. The key to reaping the antiaging, antidisease benefits of calorie restriction is getting the right amount and balance of dietary protein appropriate to your stage of life and lifestyle.

  It All Comes Down to Protein

  Longevity is not just about calories.42 (Is it ever?!) Protein restriction plays a large role in extending life span43 by slowing growth (and aging). Manipulation of dietary protein is potentially easier than restricting calories or fasting, but it has similar benefits.44 Even as early as the 1930s, animal studies showed that protein restriction can double life span.45 Mice live longest with a diet of just 5 percent protein; at that level, they also have lower rates of cancer46 and lower cholesterol.47 One specific essential amino acid, methionine, may be especially important.48 Plant-based diets are not only lower in protein but often low in methionine specifically.

  Low-protein diets might reduce cancer and mortality in humans.49 Customizing our diets—specifically our protein intake—could stave off disease and promote longer life. The key to longevity might already be in your hands. It’s not a magical berry from a far-off land. It’s not even a stringent low-calorie diet. It starts with simply optimizing your protein intake.

  Is Aging Just a Program We Can Update?

  The master program that drives growth, mTOR, doesn’t magically turn off when we’re older. It also drives aging. This growth versus longevity paradox means that the mTOR so necessary for early life may also lead to early death. But perhaps there are ways to reprogram our cells to slow aging.50 Perhaps all we need is an update in our software.

  Restricting dietary protein might promote longevity, but if taken too far, it will also inhibit normal growth and cause malnutrition. Protein deficiency can occur in isolation, or it can occur as part of a general lack of food. Overall starvation, with not only protein deficiency but also fat deficiency, is called marasmus. People become skeletally thin, with no body fat and wasting of muscle. In other situations, people get sufficient calories but very little protein.

  This issue of getting enough calories without enough protein typically occurs in children in the war-torn nations of sub-Saharan Africa that rely on food aid. These people receive mostly refined carbohydrates (which are cheap) but almost no protein (which is expensive). Food donation by First World countries typically is refined carbohydrates (sugar, flour, rice, corn), which provide calories at a fraction of the cost of protein and, importantly, do not require refrigeration during the long trip. The 1970s and 1980s saw many cases of isolated protein deficiency called kwashiorkor. African children had swollen feet, thin arms and legs (due to loss of muscle), hair loss, poor immune function, and a swollen fatty liver (due to excess carbohydrates).

  Kwashiorkor affects mostly children because of the importance of dietary protein for proper growth in infancy and childhood. Adults may break down their own protein and recycle the amino acids, but children must eat sufficient protein to grow. In developed nations, kwashiorkor is virtually absent, so we rarely see severe protein deficiency in these areas.

  As humans move into middle age, growth is no longer necessary, and it’s possibly detrimental to longevity. Low protein intake is associated with a reduction in IGF-1, as well as a reduction in cancer and overall mortality in people 65 or younger, but not in those older than 65.1

  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 30 years of age. On average, people lose 10 percent of their muscle mass per decade of life. By age 80, the typical person may have lost a full 50 percent of muscle mass. (See Figure 4.1.) Loss of muscle, known as sarcopenia, has dire consequences, including the inability to perform simple tasks of daily living, such as getting out of a chair or even standing. Lack of exercise likely plays a large role in sarcopenia, as studies of traditional societies with an active lifestyle have shown that those individuals maintain muscle mass and strength. However, in Western societies, we tend to become more sedentary with age, and we might need more protein due to a phenomenon known as anabolic resistance.

  Fig. 4.1: Muscle mass and aging

  Anabolic resistance is the phenomenon in which sufficient dietary protein, and particularly the amino acid leucine, results in less muscle growth (anabolism) in older people than in the young. Most tissues of the body, including muscle and bone, are in a constant state of breakdown and repair. For example, cells called osteoclasts break down bone tissue, whereas other cells called osteoblasts lay down new bone. Sometimes this renewal cycle moves slowly, and sometimes it can be accelerated, as with fasting.

  Fasting decreases insulin and mTOR and activates the breakdown of protein. The body has some amino acids in the bloodstream at all times, and when eating is resumed, the high growth hormone levels help rebuild muscle to replace that which was lost. If you are doing exercise, then the muscle is rebuilt to carry more weight. We should emphasize that this cycle involves small amounts of muscle. You are not in danger of losing much, if any, muscle mass through periodic short-term (i.e., 24-hour) fasting. This renewal cycle is similar to autophagy, which happens at a subcellular level and involves organelles and mitochondria. In older people, anabolic resistance means more protein is necessary for this cycle of muscle breakdown and growth. Eating more protein can help older people overcome this phenomenon.

  Restricting calories is not the same as restricting protein. Members of the Calorie Restriction Society (CRS), which was founded in 1993, deliberately restrict calories for longevity and wellness. They don’t follow a low-protein diet, however. Scientific studies found their protein intake rather high at 1.7 grams per kilogram of body weight per day compared to 1.2 grams on a typical Western diet and only 0.8 gram on a vegan diet. The CRS group’s IGF-1 levels were not much different compared to a standard Western diet.2 Only the vegan group showed decreased IGF-1. When some of the CRS group decreased their protein intake to 0.95 gram, their IGF-1 levels dropped by 22 percent and measured only slig
htly higher than the vegan group. Protein intake is critically important for IGF-1 levels in humans, despite calorie restriction. The vegan group in the study consumed more calories but less protein than the CRS group. And the protein they consumed was only plant protein. So lowering IGF-1 seems to have more to do with protein restriction than calorie restriction.

  While the decrease in IGF-1 that’s observed with lower protein intake appears encouraging, the relation between IGF-1 and longevity is still unproven. Yet the Laron dwarfs we mentioned in Chapter 2 are an example of the importance of low IGF-1 levels for cancer and other diseases of aging.

  Aging and Amino Acids

  Proteins are composed of individual amino acids, and certain amino acids are worth discussing in more detail.

  CYSTEINE

  The nonessential amino acid cysteine is crucial for the formation of glutathione (the body’s internal antioxidant), which tends to decline with age. When the body is depleted of glutathione, it’s less able to handle oxidative stress, and eating more cysteine may help solve this problem. The close association among aging, oxidative stress, and cysteine has even led some scientists to deem aging a “cysteine deficiency syndrome”; ensuring an adequate supply of cysteine might go a long way toward ameliorating the maladies of aging. Cysteine is in most high-protein foods; for example, meat, dairy, onions, broccoli, Brussels sprouts, and oats are high in cysteine.

  LEUCINE

  The amino acid leucine plays a key role as a signaling molecule in muscle growth and critical processes such as autophagy. Together, leucine, isoleucine, and valine are known as branched-chain amino acids (BCAAs). All three BCAAs are essential amino acids and are important for building muscle.

  Specific situations in which more BCAAs are useful include those situations in which a great deal of growth is desired. Bodybuilders often take whey supplements, which contain large amounts of leucine. Burn victims often lose massive amounts of protein, and supplementing with leucine might be a useful strategy to increase growth of new tissue.3 Whey also can be useful for the elderly and ill due to its growth-promoting effects on mTOR.

  METHIONINE

  The amino acid methionine is one of the nine essential amino acids. Restricting methionine, even without overall caloric restriction, has the astounding ability to increase life span in certain species, including the fruit fly and mouse.4 Methionine-restricted animals have less body fat and better insulin sensitivity and metabolism. Methionine is in meat, eggs, fish, some nuts, seeds, and cereal grains. Fruits and vegetables, including legumes, although otherwise protein dense, contain little methionine. This offers the tantalizing possibility that dietary changes could extend human life span. However, since methionine is an essential amino acid, you cannot eliminate it from the diet entirely. (Remember, essential amino acids are the type of amino acids that your body cannot make.)

  GLYCINE

  Glycine is the most important nonessential amino acid. It represents 11.5 percent of the total amino acids in the body and is an important precursor for vital proteins such creatine (in muscle), glutathione (an antioxidant), and heme (in blood). Glycine supplementation appears to be particularly unique, as it may afford protection against dietary fructose in animal models.5 And considering that the typical American consumes around 50 pounds of fructose per year, the protective potential of glycine supplementation is advantageous.

  Glycine is also important for the skin and joints. Gelatin, such as that found in Jell-O brand desserts, is a particularly rich source of glycine. It is produced by boiling the bones and skins of cows and pigs. Bone broth is also a good dietary source of glycine. Horses’ hooves, despite the popular myth, do not contain sufficient collagen, the connective tissue around the joints, to be used in the production of gelatin. In Asia, tendons, high in glycine, are prized delicacies.

  Methionine lowers glycine levels by reducing absorption and increasing excretion. Some of the benefits of methionine restriction might be due to higher glycine levels. Glycine might mimic methionine restriction by changing amino acid metabolism. Increasing the glycine content of diets might offer an easy way to obtain the effects of methionine restriction and, thus, life extension.

  All these amino acids play a role in normal human metabolism. We must get enough protein to stay healthy, but the million-dollar question is how much protein is too little, and how much protein is too much?

  How Much Protein Is Too Little?

  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. For the average man, that amounts to about 56 grams of protein a day; for the average woman, it’s about 46 grams. This is not the same as 46 to 56 grams of meat, because protein makes up only about 16 to 25 percent of the weight of meat, depending upon the type and the leanness. If you eat 56 grams of steak, you’re not getting a full 56 grams of protein. You require about six times more by weight (approximately) to offset the portion of the steak that’s not protein. How did the Institute of Medicine come up with this RDA of 0.8?

  You can estimate the amount of protein you need from the amount your body loses on a daily basis, assuming you are maintaining weight rather than losing or gaining it. Protein losses can be measured by checking nitrogen losses in the urine and stool. Carbohydrates and fat are composed mainly of carbon and hydrogen, whereas protein is the major source of nitrogen in the body. In 1985, the World Health Organization found that daily losses of protein averaged 0.61 gram per kilogram per day. Presumably, then, a person’s diet should replace (roughly) this 0.61 gram per kilogram per day that’s lost. This average is for normal healthy people, not for people who are losing muscle or otherwise are sick.

  To build in a margin of safety against protein deficiency, the World Health Organization added 25 percent (two standard deviations) more than the 0.61 gram per kilogram per day value, which is approximately 0.8 gram per kilogram per day. Based on the original calculations, 97.5 percent of the healthy general population was eating less than 0.8 gram per kilogram per day of amino acids. This value is not a low standard. This is a very high standard of sufficient protein intake, and the value was calculated on the assumption that excess dietary protein is not dangerous.

  Even at this high level, the average man still required only 56 grams of protein and the average woman only 46 grams. For reference, the USDA in 1985 determined that in the United States, 14 to 18 percent of calories came from protein, and the average consumption was 90 to 110 grams per day for men and 70 grams per day for women. Americans, being one of the wealthiest populations on Earth, were eating much more protein than the average inhabitants of this planet. The average American male was eating twice the recommended daily amount, which itself is already a high estimate of our actual needs. This happens day after day. Week after week. Year after year.

  Furthermore, in adults, our bodies continuously degrade and resynthesize intrinsic body proteins. Old proteins are broken down, and the amino acids are reabsorbed to be built into new proteins. The amount of turnover is several times larger than the amount of amino acids we eat daily. However, some amino acids do get lost in the process, predominantly in the stool and urine. During periods of low protein intake, the amount of nitrogen lost in the stool and urine can drop to a very low level, which explains how adults in sub-Saharan Africa largely avoided kwashiorkor despite extremely low protein intake. Their bodies were recycling their own amino acids to build new proteins. So, the lower limit of protein needed to maintain health is largely still unknown, but it might be far lower than 0.61 gram per kilogram per day.

  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.6 For example, if someone weighs 200 pounds and has 25 percent body fat, that would imply 75 percent lean mass. Total lean mass is then simply calculated li
ke so:

  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.

  These recommendations differ due to individual differences and the type of protein consumed. Animal protein is a more digestible and complete source of protein, so we likely require less. We likely require more plant proteins (such as from soy or legumes) because of its lower absorption (bioavailability).

  So, should you worry about protein deficiency? Not really. In the United States, the average person eats approximately twice the RDA, which itself is designed to be higher than a healthy person needs. If we start seeing a North American outbreak of kwashiorkor, we’ll start worrying. So, this brings us to the opposite question.

  How Much Protein Is Too Much?

  Excess protein, beyond what you need to maintain structural tissues such as muscle, is metabolized for energy or stored as glycogen or fat. Like excess carbohydrate or sugar, excess protein might lead to metabolic problems like obesity and type 2 diabetes. A low-carbohydrate diet might resolve many of these problems, such as insulin resistance and obesity, by allowing fat to be used preferentially as an energy source; low-protein diets might be beneficial in the same way.7

  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.