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Eat Less To Live Longer ; Calorie Restriction Mimetics - A Novel Approach

Updated on February 15, 2016

Calorie Restriction With Adequate Nutrition


Calorie Restriction Slows The Aging Process

Aging is a decline in the power of self-maintenance, and an increase in susceptibility to disease. Modern theories of aging fall into two categories, which start from opposite poles.

The first views aging as an ordered process delicately programmed by the genes, the second suggests that aging is caused by the progressive retention and amplification of errors in the replication of genetic information in our cells.

Principles Behind Calorie Restriction

  1. Hormesis - It is derived from a Greek word that means,"to excite". It proposes that a low-cal diet imposes a low-intensity biological stress on our body, which elicits a defensive response that helps protect it from aging. This switch to a defensive state may be controlled by the longevity genes.
  2. Free Radical Theory - In May 2007, a multicenter clinical trial called the CALERIE (Comprehensive Assessment of the Long-term Effects of Reducing Energy Intake)study was begun, to examine the effects of two years of sustained 25% calorie restriction on - Slowing the aging process, and protecting against age-related disease processes. When we eat in excess, the food gets digested, absorbed, and assimilated from intestines, and a high amount of energy is produced, which disrupts the work efficiency of mitochondria (the powerhouses of cells)and generates more superoxide and hydroxyl ions. These are called free radicals or Reactive Oxygen Species (ROS). These electronically charged molecules cause severe cell damage. With calorie restriction, less amount of energy is generated, and there is less free radical generation.
  3. Non-enzymatic glycation - This is a complex process that involves condensation of sugars and protein amino groups, resulting in brown discoloration, and a loss of function and degradation of proteins. A calorie-restricted person has less body fat, a lower body weight, and requires less amount of energy to support this weight. Also, the blood glucose levels remain normal. Less blood glucose means less glycation of adjacent proteins, and less fat being oxidized in the bloodstream to cause sticky cholesterol plaques that result in atherosclerosis. People with type-2 diabetes develop insulin insensitivity or resistance due to long-term exposure to high blood glucose. Eating less amount of calories tends to reduce this disease condition.
  4. Reduced DNA damage - Calorie restriction reduces the production of Reactive Oxygen Species that are responsible for DNA damage.
  5. Calorie Restriction and Sirtuins - sir-2 or silent information regulator-2 is a sirtuin found in barber's yeast, that is hypothesized to reduce DNA instability.

Complications of Calorie Restriction

A total calorie intake, that is around 70% of the daily requirement (with adequate nutrition) does not cause any deleterious effects.

But when the calorie intake falls to 30-45% of the required, then dangerous complications can develop as shown in the Minnesota Starvation Experiment.

Severe restriction of calories has some positive metabolic adaptations like a reduced body fat, lowered blood pressure, improved lipid profile, low serum T3 concentration, reduced heart rate, and low whole body resting energy expenditure.

But it can cause certain severe adverse effects, like anemia, swelling in legs and feet, muscle wasting, weakness, dizziness, irritability, lethargy, and depression.

The Traditional Okinawa Diet

Okinawa Diet

This is a weight loss diet based on the eating habits of Okinawans, the indigenous people of the Ryukyu Islands, who are known to have a high life expectancy.

This traditional diet contains 30% green and yellow colored vegetables; smaller quantities of rice; and their staple is the purplish colored sweet potato. This diet also includes tiny amounts of fish (less than half a serving per day), and more of soy and legumes (6% of total calories). The daily diet is almost entirely plant-based.

Okinawans consume fewer calories than average (1785 cal as compared to 2068 calories which is the average daily consumption of a normal adult), less polyunsaturated fat, less rice, significantly less amount of wheat, barley, and other grains, less sugars, less meat, poultry, eggs, and dairy, less other proteins, less fruit, and no pickled vegetables.

The calorie consumption of an average Okinawan is 1 calorie per gram of food, who has a BMI (Body Mass Index) of about 20 in early adulthood.

This traditional diet has a protective effect against diabetes, high blood pressure, metabolic syndrome, and certain cancers, which are the results of our urban fast food culture.

Hara Hachi bu

This is a norm of the traditional diet that instructs people not to stuff themselves with food, but to eat until they are 80% full.

Okinawans in Japan, through practicing Hara Hachi bu, have a self-imposed habit of calorie restriction.

Low Calorie Basics - What Things To Add To Your Food Cart?

The low-calorie food items that can form an essential part of your grocery shopping, include the following:

  • Fat-free, or low-fat milk, yoghurt, cheese, or cottage cheese.
  • Light or diet margarine.
  • Egg white or egg substitutes.
  • Whole wheat sandwich breads, bagels, pita bread, English muffin.
  • Soft corn tortillas, low-fat flour tortillas.
  • Low fat, low sodium crackers.
  • Plain cereal - dry or cooked.
  • Rice, pasta.
  • White meat, chicken, or Turkey (remove skin).
  • Fish and shellfish (not battered).
  • Dry beans and Peas.
  • Fresh, frozen, or canned fruits in light syrup or juice.
  • Fresh, frozen, or no-salt-added, canned vegetables.
  • Low-fat or fat-free salad dressings.
  • Mustard and catsup.
  • Jam, jelly or honey.
  • Herbs and spices.
  • Salsa.

Calorie Restriction Mimetics

These are a hypothesized class of medicines, that would, in principle mimic the substantial anti-aging benefits of calorie restriction.

They are believed to alter the key metabolic pathways that are involved in the effects of calorie restriction, leading to a longer and disease-free life, without the need to reduce food intake.

The candidate compounds in this category, include the following:

Resveratrol Has Effects Similar To Calorie Restriction


1. Resveratrol

This is a type of natural phenol, a phytonutrient found naturally in the skin and seeds of red grapes, peanuts, some berries, red wine, and in the roots of the Japanese knotweed, from which it is commercially extracted.

It has beneficial effects against diseases such as type-2 diabetes, cardiovascular diseases, and cancer. It helps reduce inflammation, prevent oxidation of LDL, and platelet stickiness.

Resveratrol is also a nerve strengthener that protects the neurons from damage and prevents the build-up of plaques that can lead to Alzheimer's disease.

It also helps prevent insulin resistance, a condition in which our body becomes less sensitive to the effects of this sugar-lowering hormone.

As per a recent study, most of these effects of Resveratrol are mediated by inhibiting cAMP-phosphodiesterase enzyme (cyclic Adenosine Mono Phosphate) PDE4.

It also acts as a calorie restriction mimetic and helps combat some effects of unhealthy diet to promote longevity. It does so, by regulating the activity of enzymes called sirtuins, which in turn control several biological pathways, and are involved in the aging process.

Resveratrol is one of the many natural and synthetic Sirtuin-Activating Compounds (STACs). SIRT-1 acts in the cells by removing an acetyl chemical group from its protein substrates. STACs or the enzyme activating compounds ultimately increase the activity of mitochondria, the organelles that produce energy for cell functions, and protect our bodies against the harmful effects of obesity and aging.

Resveratrol exhibits drug interactions with blood thinners, such as warfarin, and non-steroidal anti-inflammatory medicines, such as ibuprofen and aspirin, increasing the risk of erosions in the inner lining of the stomach and internal hemorrhages.

2. Anti Diabetic Medicine Metformin

Metformin or 1,1-dimethyl biguanide hydrochloride is a clinically approved medicine for type-2 diabetes. It reduces both, the fasting (empty stomach) and postprandial (after meals) blood glucose levels in people with type-2 diabetes, but has no effect on fasting blood glucose levels in normal individuals.

It acts as a Calorie Restriction Mimetic by reducing glucose production in the liver from fats and proteins (hepatic gluconeogenesis), slows down glucose absorption from the digestive tract, enhances the sensitivity of insulin receptors on the surface of muscle and fat cells, and increases glucose uptake by skeletal muscles.

It thus reduces the risk of non-enzymatic glycation and other age-related damage. Metformin intake should be avoided in people with type-1 diabetes, those with compromised kidney and liver functions, alcoholism, and cardiorespiratory insufficiency.

This medicine is not totally free of side effects, which include loss of appetite, nausea, vomiting, abdominal discomfort, and lactic acidosis (a form of ketoacidosis that can occur after metformin intake in individuals with associated diseases of kidneys, liver, cardiac problems, alcoholism, and in advanced age).

3. 2-deoxy-D-Glucose

It is a glucose analog that inhibits the breakdown of glucose (glycolysis) and can mimic at least some effects of calorie restriction, in particular, increased insulin sensitivity, reduced blood glucose levels, a decrease in body temperature, and other biological changes.

4. Rapamycin

Also known as Sirolimus, it is a macrolide produced by the bacterium Streptomyces Hygroscopicus that lowers body immunity and is used to prevent graft rejection in organ transplant recipients.

It inhibits the response to IL-2 (Interleukin-2, a chemical mediator of inflammation) and blocks the activation of white blood cells (T- and B-lymphocytes, the soldiers of our immune defense system).

It inhibits the mechanism Target Of Rapamycin (mTOR)pathway, that is the proposed mechanism for its calorie restriction mimetic effects.

Portion Control For A Long And Healthy Life

Modern calorie restriction with adequate nutrition is the only non-genetic, non-pharmacological intervention to protect our body from deterioration of biological functions, delaying or reducing the risk of many age-related diseases, and extending the lifespan.

The biological mechanisms which are most affected by this process include energy metabolism, oxidative stress, insulin sensitivity, inflammation, and neuroendocrine markers.

Calorie restriction, along with a nutritious diet that is rich in essential proteins and vitamins has a powerful effect against obesity, type-2 diabetes, inflammation, high blood pressure, cardiovascular diseases, and certain cancers.

The key markers of a calorie restricted phenotype, the plasma insulin, dehydroepiandrosterone sulphate, and body temperature, may predict longevity and good health.

Reference Sources:

"History and Characteristics of Okinawan longevity food"' Asia Pacific J. Clin. Nutr.

"Substrate-specific activation of sirtuins by resveratrol" Journal of Biological Chemistry.

"Healthy Eating Starts with Health food Shopping" National Heart, Lung, and Blood Institute.


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    • shraddhachawla profile imageAUTHOR


      3 years ago

      Like there are always two sides of a coin, there are both views in support of, and against Caloric Restriction. According to a study by national institute on aging "calorie restriction does extend some aspects of health". This especially holds true for heart diseases and cancer. Conventional blood markers of aging such as excess glucose, cholesterol, triglycerides, and LDL or bad cholesterol can be maintained within normal range following by calorie restriction. The opponents of this regime believe that it could cause nutrient deficiencies, loss of lean muscle and increase risk of developing eating disorders. It depends more on the food choices you make. Cutting down on foods that provide empty calories like sugar, refined flour, processed food, junk food and adding nutrient dense super foods to the diet can help avoid the risk of deficiencies. Food items with high biological value such as eggs and milk that are highly efficient in the synthesis of body proteins can help prevent loss of lean mass. Thank you for your valuable feedback promisem. Have a great day.

    • promisem profile image

      Scott S Bateman 

      3 years ago

      I read recently that calorie restriction as an anti-aging therapy has lost some credibility as a result of the latest studies. Do you agree?

      The other point I would make is that 70% of daily requirements sounds extreme, but it depends on the person's metabolism. Various online tools claim I need close to 2,000 calories a day based on my height, but I seem to maintain a normal weight at about 1,500 calories, which is 75% of 2,000.

    • profile image


      3 years ago

      'Eating too much is the root of much of the problems we have today.

      Being a muslim I believe in each and every word of Quran & Hadith or Sunnah (Prophet muhammed's teachings)... There are many Ayats (verse) in Quran that gives clear instruction regarding our Eating habits ...The Prophet (peace and blessings of Allaah be upon him)has explained that :

      'We don’t need to eat more than a few bites to stay alive and fit.

      The Prophet (peace and blessings of Allaah be upon him) also explained how the believer should be with regard to food and drink, as he said:

      “The human being does not fill any vessel worse than his stomach. It is sufficient for the son of Adam to eat a few mouthfuls, to keep him going. If he must do that (fill his stomach), then let him fill one third with food, one third with drink and one third with air.”

      (Narrated by al-Tirmidhi and classed as saheeh by al-Albaani in Saheeh al-Tirmidhi. )

      And the Prophet (peace and blessings of Allaah be upon him) forbade every harmful thing, whether that is food, drink or anything else. He said: “There should be neither harming nor reciprocating harm.” (Narrated by Ibn Maajah (2340) and classed as saheeh by al-Albaani in Irwa’ al-Ghaleel (896).

      The food may be halaal in principle, but because of extravagance in eating it that leads to harm, it may be haraam. This does not apply only to meat; everything that will cause harm to a person if eaten is haraam, even dates.


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