CR Way Research

The life-extending and disease-prevention benefits of calorie restriction are often used as the gold standard for animal research on aging. In such studies, calorie-restricted animals are compared to controls to see if an intervention like a drug or supplement has a life-extending effect or other disease-preventing benefit similar to CR.

This made us wonder if such a standard could be established in humans. The problem, of course, is that unlike favorite research animals like mice, flies or worms, humans have a long life span, so waiting a lifetime to see if calorie restriction really works isn't practical. People who want to slow aging need answers now! They need to know what works and what doesn't and they need a gold standard that can be used to evaluate any anti-aging intervention worth considering. This is the reason for CR Way Research, which began in 2002.

Initially we started with a pilot study run by the eminent Dr. Richard Lord at the Metametrix Clinical Laboratory. Subsequently we formed a partnership with Drs. Luigi Fontana and John Holloszy at the Washington University in Saint Louis School of Medicine. Here, Dr. Holloszy has developed a superb laboratory for human research—perfect for human CR studies. Thus what would eventually become CR Way research was off and running.


Luigi Fontana , M.D., Ph.D ., - principal investigator

Dr. Fontana has gained special insights on human health from his experience as a practicing physician and as a researcher in metabolism. His passion is the science of aging. Dr. Fontana has already made medical history by publishing the results of the first phase of the project, which show that calorie restriction does indeed have age-slowing effects in humans.



The results have attracted worldwide attention:


  1. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans.

    Proceedings of the National Academy of Sciences of the U. S. A. 2004 Apr 7; 101(17):6659-63.

    Fontana L, Meyer TE, Klein S, Holloszy JO. PMID: 15096581

    The group from the Calorie Restriction Society showed virtually no evidence of risk for atherosclerosis. Many evaluative measures such as total cholesterol, LDL, triglycerides, insulin and high sensitivity C-reactive protein were significantly lower in the CR group, while the cardio-protective HDL was higher. Our carotid artery wall thickness, a diagnostic indicator for coronary artery disease, was 40% less than that of the controls, and we showed no evidence of plaque accumulation.
  2. Long-term caloric restriction ameliorates the decline in diastolic function in humans.

    Journal of the American College of Cardiology. 2006 Jan 17;47(2):398-402.

    Meyer TE, Kovacs SJ, Ehsani AA, Klein S, Holloszy JO, Fontana L. PMID: 16412867

    Decline in the heart's diastolic function occurs with age. The results of this study showed that the diastolic function of our CR cohort resembled that found in people about 15 years younger.
  3. Effect of long-term calorie restriction with adequate protein and micronutrients on thyroid hormones.

    J Clinical Endocrinology and Metabolism. 2006 Aug;91(8):3232-5. Epub 2006 May 23.

    Fontana L, Klein S, Holloszy JO, Premachandra BN. PMID: 16720655

    “Thyroid hormones influence cell respiration, free radical production and energy homeostasis. Data from long-lived rodent studies shows that CR decreases serum concentrations of T3, the hormone that mediates most of the functions of the thyroid gland.

    This study showed that the serum level of the thyroid hormone, triiodothyronine (T3) may be as a human aging indicator. Consistent with the studies of calorie-restricted animals, the T3 hormone of our calorie-restricted group was found to be lower than the control groups.
  4. Aging, adiposity, and calorie restriction.

    JAMA—Journal of the American Medical Association . 2007 Mar 7;297(9):986-94. Review.

    Fontana L, Klein S. PMID: 17341713

    Here, Drs. Fontana and Klein used observations of our group as well as other studies to set parameters for healthy calorie restriction – important for anyone who wishes to practice the lifestyle.


Drs Joseph Dhahbi and. Stephen R. Spindler lead genetic testing

Drs.Joseph Dhahbi and Stephen Spindler, whose genetic analysis of calorie-restricted animals has garnered worldwide acclaim, are leading the exploration of the cell-signaling patterns of human calorie restrictors for phase three of CR Way research into calorie restriction. Building on years of studying calorie restriction in work on animals, Drs Dhahbi and Spindler will provide an incisive look into how CR calorie restriction affects genetic expression in calorie-restricted humans.

For those interested in finding out more about Dr. Spindler's and Dr. Dhahbi's work, take a look at these two marvelous research papers that report on the genetic expression patterns of calorie-restricted animals: 

  1. Temporal linkage between the phenotypic and genomic responses to caloric restriction.

    Proceedings of the National Academy of Sciences of the U. S. A . 2004 Apr 3;101(15):5524-9.

    Dhahbi JM, Kim HJ, Mote PL, Beaver RJ, Spindler SR. PMID: 15044709

    Dr. Spindler and his colleagues showed that CR acts rapidly, even in old mice, to extend remaining lifespan by 42% and to dramatically reduce tumors as a cause of death. They found that gene expression also changes rapidly to a new pattern which is closely associated with lower cancer mortality and better health.
  2. Gene expression and physiologic responses of the heart to the initiation and withdrawal of caloric restriction.

    The Journals of Gerontology. Series A: Biological Sciences and Medical Sciences. 2006 Mar;61(3):218-31

    Dhahbi JM, Tsuchiya T, Kim HJ, Mote PL, Spindler SR. PMID: 16567370

    Here, Dr. Spindler and his research team used Affymetrix microarrays as well as biochemical and histological studies to show that CR rapidly changes cardiac gene expression and physiology to reduce cardiovascular damage, fibrosis, and blood pressure, and to enhance cardiac contractility and energy production . These results indicate CR has rapid, positive effects on the heart.

These great researchers use the latest analytical methods to determine what's happening at the genetic and cell-signaling levels in human calorie restrictors. To provide subjects, we rallied the CR Way membership to participate and developed a method of screening participants that required proof of health status and limitation of calories. We were able to form a cohort of CR members, who have lived the CR Way for six or more years.

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