You Are What You Don’t Eat

Longevity scientists and seekers have been exploring any number of routes towards increasing healthful years and, ultimately, living beyond the normal biological lifespan for humans. One of the methodologies that has caught on with some who are on the longevist path is caloric restriction — generally understood as taking in considerably fewer calories than normal.

The method, of course, has its advocates and detractors (tomorrow, we will be running an article by a critic). But it has gained enough credibility that a company, Sirtris Pharmaceuticals, has been developing medicine that is, at least, partly based on caloric restriction.

Averill and McGlothin’s book, Living The CR Way: Using the Secrets of Caloric Restriction for a Longer, Healthier Life, released April 2008, contains dietary recommendations, as well as advice about other activities that the authors claim followers of the CR Way can use to ensure getting the full benefits of CR.

McGlothin says he "had the good fortune" to come into contact with one of the country’s leading internist, who is a calorie restrictor. It was through this physician that McGlothin and Averill both became smitten with CR practice and science and surrounded themselves with a team of doctors in an attempt to sort out fact from fiction in the practice.

They also initiated the first CR study of humans, accomplished with MetaMetrix Clinical Laboratory in 2001. Subsequently, they formed a partnership with Drs. Luigi Fontana and John Holloszy at the Washington University in Saint Louis School of Medicine. During this period McGlothin worked with multiple labs to create a pilot study on Resveratrol that was reported at the 2004 CR Society Conference. His work in testing CR results led to his being named Research VP of the CR Society, where he works with scientists to plan studies. He will present at Harvard Medical School’s Aging &Healthy Lifespan Conference (See References) in September 2009. Averill chaired the Board of Directors of the CR Society International and is credited with spreading that groups influence by supporting regional, national, and international CR Society groups around the country and the world

h+: For absolute beginners, tell us a bit about the history of the idea of caloric restriction as a method for longevity?

MEREDITH AVERILL/PAUL MCGLOTHIN: Roy Walford, Ph.D. gerontologist and Father of CR for Humans, studied calorie restriction in mice at UCLA and was awarded many honors for his work. He saw that mice and monkeys, both mammals, shared greatly improved health and longer life when maintained on a CR diet.

Dr. Walford was a pioneer in the field of CR for human longevity. He was also the only physician in the Biosphere experiment, which turned into the first human CR experiment. Biosphere 2, which ran from September 1991 through September 1993, provided the first insights into the effects of CR on people. He learned that humans, when limiting their calories, also display the same effects on their blood-level markers that are characteristic of CR in the other two species of mammal.

But Walford’s work is recent… and the history of CR as a method for longevity really started 74 years ago. In 1935, Dr. Clive McKay and his colleagues reported their findings that the lifespan of mice was lengthened when their food was limited. Almost three-quarters of a century has passed and science has not yet provided a full explanation of how CR extends life. It could be years before the complete answer is found.


This is not what humans in the current era who hope for cures for age-related disease and decline want to hear. To accelerate the search for longevity therapeutics, many researchers bypass the fundamental question of how CR slows aging to focus on identifying regulators that control calorie restriction’s beneficial effects. To identify important breakthroughs – one of them involves Insulin and Insulin-like Growth Factor (IGF-I), hormones that have major effects on growth and metabolism.

In 1992, Cynthia Kenyon identified a biochemical pathway, similar in function to the insulin/IGF-I pathway in humans, as an aging regulator in C. elegans, a roundworm that is very helpful for longevity studies because of its short lifespan. Changes in the related gene resulted in doubling the lifespan of the roundworms. Subsequent studies have confirmed the importance of the insulin/IGF-I pathway for regulating aging in a wide spectrum of species including humans.

And then there’s SIR2. In 1999, two graduate students in Leonard Guarente’s lab at MIT discovered the enzyme SIR2 (Silencing Information Regulator) to be a regulator of aging in yeast. Later studies confirmed that SIR2 homologues (sirtuins) were evolutionarily conserved in many mammalian species including humans, where seven sirtuins have been identified: SIRT1–SIRT7.

In 2003, resveratrol, the phytosterol found in red wine, was seen to stimulate SIR2 potently in yeast, increasing lifespan without calorie restriction – a striking advance for practical application of CR science: could it be that a true calorie restriction mimetic – a substance that mimics the effect of CR without the need to limit calories – had been discovered? Adding credence to this notion, a 2006 study found that resveratrol extends the lives of mice placed on a high-calorie diet.

h+: Caloric restriction is still controversial. A number of biologists have come forward to say it doesn’t work. Wouldn’t you agree that it is — at least — speculative?

MA/PM: The animal data on health and longevity are incontrovertible, and the Homo sapiens studies show that humans get the same health results as the animals, so extended life is likely. The preliminary results of the rhesus monkey study, which were recently reported, show that the monkeys fed CR diets are healthier and are dying more slowly than the control animals. Although human lifespan studies are a long way from completion, we already have excellent epidemiological evidence that calorie restriction extends life.

Some of the best research has been done by Dr. Brad Willcox, who has spent much of his research career studying the famously long-lived Okinawans whose culture ingrained into their lives the hara hachi bu practice: Eat only until you are 80% full.

Closer to home, the longest-lived member of the CR Society, Ralph Cornell, followed that same philosophy. He said his most important exercise was the Thumb Exercise: He pushed himself away from the table with his thumbs when he started to get full. And he lived 104 healthy years.

But for a minute, let’s ignore all the evidence that CR extends life. We would still follow The CR Way ardently. “Why would we do this?” one might ask. Because it makes life better right now. Brimming with energy is wonderful and to be able to do just about anything you want — no matter what age you are — is worth leaving a few calories uneaten, especially when the ones eaten are soo delicious.

Any skeptic need only try the diet for a couple months – testing such benchmarks as blood pressure, heart rate, and glucose before starting and at the end of the test period, for comparison. The differences will be striking. Besides, they’ll know by how great they feel.

h+: So what does your specific program, the CR way, bring to the party?

MA/PM: The CR Way makes the benefits of the new advances in CR science accessible to everyone. Showing people how to start a healthful, low-calorie diet is part of what The CR Way offers. We also help them keep it going. The CR Way leads people to create a lifestyle that integrates a nutrient-dense, low-calorie diet with meditation, yoga, exercise, and other strategies that improve healthspan. The CR Way encourages enthusiasts to plan programs that fit their needs and lives.

For transhumanists, The CR Way is especially important because we can use it to affect how we live, how well we live, and probably how long we live in our current human form. The new science shows that limiting caloric intake shifts the body’s emphasis from cell proliferation and growth to cell maintenance and more effective cellular function. Humans can apply this knowledge to get transformative effects.

Consider these new “aging” health standards that may seem like science fiction… heart function improves – age-related loss of cells slows; blood pressure of 98/62 or lower. Arterial plaque accumulation remains static or reverses. Muscle strength maintains or increases with no lasting soreness or pain from exertion – age-related cell loss slows. Cellular energy production increases. Immune function increases – quick reaction to immune challenges; inflammation markers at the low end of reference range. Risk of heart disease, cancer, diabetes, and Alzheimer’s disease lowers. Youthful hormone secretion ability preserved. Stronger skeletal system – bone density increases gradually with stronger matrix likely. These are dramatic physical transformations. We’ve seen psychological and cognitive benefits too.

h+: How do you substantiate these claims?

MA/PM: We want everything we do to be backed by solid scientific research and testing. That is why we helped set up the first longitudinal study of calorie-restricted humans. Now, for the past seven years, we and a cohort of other calorie-restricted humans have been thoroughly tested by teams of scientists headed by Drs. Luigi Fontana and John Holloszy at the School of Medicine at Washington University in St. Louis. (See Resources)

As you can see from the report, The CR cohort has been studied in great detail and has been the subject of many research reports and review articles in peer-reviewed journals. Heart function, for example, which usually deteriorates in part because of age-related cell loss, has been shown in the CR cohort to be like that of much younger people. In addition to working with scientists, we also work with a team of doctors who test every aspect of our health regularly. In fact, before our appearance on the Oprah show, the producers actually called our doctors to verify eyesight improvement, increases in bone density, and decreases in blood pressure, resting heart rate, triglycerides, etc. Our results are right in line with hundreds of animal studies that get extended life and improved health with calorie restriction.

This is good. We’re happy about it. But it’s still not enough. People need to be able to verify for themselves whether any health intervention is working. So The CR Way includes a series of benchmarks — recommended lab tests that anyone who wants to try the lifestyle can use to gauge their progress.

As for cognitive and psychological benefits — excellent research by Dr. Mark Mattson, head of the Neurobiology Unit at the NIH, shows definitively that limiting calories and/or fasting induces healthy physiological changes in the brain. The CR Way recommends both of these for cognitive improvement. These benefits include: Decreased formation of damaging free radicals; better utilization of glucose by brain cells; increased secretion of biochemical or bioelectrical signals… referred to as trophic factors, that promote growth and are essential to forming new neural pathways and activation of neuroprotective genes such as SIRT1. All of these benefits lead to increased concentration, better memory, and preservation of neurons – all critical to improved cognitive skills.

In our latest creation, The CR Way to Happy Dieting, we focus on improving psychological health by increasing brain biochemistry associated with happiness. Readers get suggestions for food combinations and lifestyle practices that predispose them to positive, optimistic thought — making it easier to stick with a diet because they enjoy it.

For example, serotonin, the brain neurotransmitter that is associated with calm, happy feelings is known to play a key role in the ability to regulate food intake. We’re lucky that serotonin can be greatly increased by dietary choices, so we regularly include serotonin meals in our daily diet and provide a batch of serotonin-producing recipes in The CR Way to Happy Dieting. Additional steps to increasing happiness biochemistry include meditating to activate the left pre-frontal cortex, which has been shown by University of Wisconsin researchers to be associated with good feelings. To help The CR Way to Happy Dieting users evaluate their progress towards positive, happy thinking patterns, we include a “happiness gauge,” a simple tool to help keep people on track to real progress.

h+: Someone posted that you guys don’t eat after 1 pm, which I found a bit disturbing. Is it true? Do you recommend other people do the same?

MA/PM: We encourage people to practice the CR Way their way. This would include exploring Limited Daily Fasting by people who are especially interested in improving cognitive function.

Research shows that time away from food has very beneficial neurological effects (perhaps greater than calorie restriction alone) (See Resources) That includes stimulation of new neuron growth – wonderful for those looking to increase brain power. We prefer not to “jerk our metabolisms around” though, with extreme fluctuations of energy input — first normal then none, followed by normal and so on. So we developed “Limited Daily Fasting:” We eat a big breakfast and a somewhat smaller lunch. Then for dinner we take a walk and enjoy the social interchange that eating a meal together traditionally provides.

This meal timing may give us 15 or so hours away from food, and most people have a limited daily fast to some degree because the overnight period usually is the longest time their bodies have away from food. At least as important as the length of time of the “fast,” though, is the blood glucose levels being fairly low. This is why we emphasize glucose control. So the reality is that we don’t eat after lunch but that is rarely as early as 1 pm.

h+: With companies developing drugs that mimic the effects of caloric restriction, will the dietetic aspect of C.R. soon become obsolete?

MA/PM: Does the world really want a pill that would make sloth and gluttony easy? [ed: Yes!] There are millions of people who practice their own form of The CR Way because they actually don’t like the way they feel after overeating and they want to lead active, energetic lives.

If a calorie restriction mimetic became available tomorrow, we would not stop living The CR Way because we truly love the delicious low-calorie foods and recipes and the opportunity it provides to realize our full potential

Remember, too, that there is a big difference between calorie restriction alone and The CR Way, which offers strategies that enhance CR’s benefits. Imagine the difficulty of creating a CR Way mimetic that, in addition to standard CR’s impressive benefits, also increases happiness and optimism. Or that increases cognitive capabilities, as Centering Meditation does by activating the left pre-frontal cortex.

This does not mean we are against development of a CR mimetic – quite the contrary. We would love to get the benefits of eating fewer calories than we do now. And if some day a fully safe CR mimetic comes along that further enhances our healthy lifestyle, so much the better.

h+: Relatedly, people come in various different genetic types and have different desires and — in some cases needs — for food. So, are you working on variations for types?

MA/PM: Perfect question! The original name for our book, The CR Way, was “Calorie Restriction As You Like It." Now that’s the title of the third chapter of the book. This new approach reflects that we are all different and is intended to help people put the new science into practice in a way that works for them. Some choose to follow The CR Way for healthful weight loss, while others want to protect against major diseases like cancer or diabetes. Transhumanists anticipate a glorious future. They may travel The CR Way to have the very best chance of living to be part of the singularity that is to come.

One of the most important lessons to be learned from The CR Way is that millions of people, whether or not they identify themselves as calorie-restricted, are already limiting calories enough to get phenomenal health benefits. However food, lifestyle, and other choices prevent them from activating CR biochemistry. Usually making only slight changes will unleash a flood of benefits. And even if people decide they can’t follow the CR Way, understanding the science behind the benefits would let them avoid expensive mistakes that could cost them their lives.