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Calorie Restriction Research Moves forward!


The CR Society International is the leader of calorie restriction research in humans. The CR Society Research projects are the first and remain the only longitudinal study of long-term human CR practice. To discuss a human calorie restriction research project, please contact: research@crsociety.org


The first CR Society Research study launched in 2002, with Doctors Luigi Fontana and John Holloszy, at the famed Washington University Medical School in Saint Louis tested the hypothesis that CR produces the same positive effects in humans as it does in laboratory animals. It compared serious CR practitioners with age-and sex-matched controls. The results have been widely reported in the medical literature.


Calorie Restriction Research project: Current investigators:


Luigi Fontana, M.D., Ph.D. (http://geriatrics.im...ty/fontana.html).

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 with the first phase of the project by showing that calorie restriction does indeed have age-slowing effects in humans.

The results have been reported worldwide in the medical literature:

  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 used 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. Long-term effects of calorie or protein restriction on serum IGF-1 and IGFBP-3 concentration in humans.
  5. Aging Cell. 2008 Oct;7(5):681-7.
    Fontana L, Weiss EP, Villareal DT, Klein S, Holloszy JO. PMID: 18843793
    … [O]ur data provide evidence that protein intake is a key determinant of circulating IGF-1 levels in humans, and suggest that reduced protein intake may become an important component of anticancer and anti-aging dietary interventions. "It's much easier to restrict protein than to restrict calories," he says. "If our research is on the right track, maybe humans don't need to be so calorie restricted. Limiting protein intake to .7 or .8 grams per kilogram per day might be more effective. That's just a hypothesis. We have to confirm it in future studies."

We are now in phase 3, which continues the clinical testing – providing more data for the longitudinal analysis. Phase 3 also looks at the genetic effects of long-term CR in humans. We eagerly await the test results from Doctor Fontana to find out how serious, long-term CR affects cell signaling.



New Projects


Meanwhile two other exciting human CR projects have been launched and rapidly move forward.


1. Cell Signaling exploration with genetic experts, Doctors, Stephen Spindler and Joseph Dhahbi.


Drs Dhahbi and Spindler, whose genetic analysis of calorie-restricted animals garners worldwide acclaim, lead the exploration of the microRNAs of human calorie restrictors in a new phase of the Calorie Restriction Project. Building on years of studying calorie restriction in animals, Drs. Spindler and Dhahbi will provide an incisive look into how calorie restriction affects genetic expression in calorie-restricted humans.


For those interested in knowing more about their work, take a look at these two 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
    Drs Dhahbi,Spindler and their 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, Drs. Dhahbi, Spindler and their colleagues 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. We eagerly anticipate the study results, which we believe will reveal much about what's happening at the genetic and cell-signaling levels in human calorie restrictors. We hope that the information we reveal will provide serious longevists everywhere with scientifically verified ways to evaluate anti-aging interventions.

2, The Society is honored to partner with the CR Way on

CRONA (Caloric Restriction With Optimal Nutrition & Aging)– a milestone study that Looks at The Genetic Effects Of Caloric restriction from a different perspective , focusing on telomerase, telomere length and many other markers in a cohort of long-term serious calorie restrictors.


Headed by Dr. A. Janet Tomiyama at the University of Rutgers, the project includes:

Elizabeth Blackburn (, Nobel prize winner, Biochemistry & Biophysics, UCSF)

Anne Brunet (Dept of Genetics, Stanford)

Elissa Epel (Psychiatry, UCSF)

Pankaj Kapahi (Buck Institute for Age Research)

Cynthia Kenyon, (Biophysics and Biochemistry, UCSF)

Jue Lin (Biochemistry & Biophysics, UCSF)

Eric Verdin (Gladstone Institute of Virology and Immunology at UCSF)








Meredith Averill and Paul McGlothin thank Drs. John Holloszy and Luigi Fontana

for their outstanding explorations of calorie restriction in humans. Meredith and Paul

led the fundraising effort to support the study. This photo is from their most recent

visit to Washington University as CR cohort participants.

Think of where we were in 2002, before the Society's research involvement began. There was little proof that CR really worked in humans. Now the results of the CR Research project provide tantalizing evidence that CR has profound health-enhancing and age-slowing benefits in humans. Indeed, the research results have been reported around the world – influencing the direction of additional research and providing vital guidance for anyone interested in better health.


Although there are many opinions about the best ways to practice CR, we all agree that there isn't a second to lose in pursuing research that will help us understand how to slow aging and prevent the diseases that so frequently come with getting older.


New Research projects


In addition to the current research project, the Society seeks additional collaborations that will stop the ravages of aging and extend healthy lifespan. We welcome contact from interested researchers and supporters who believe that not a minute should be lost in pursuing answers that will help us all live longer and better.

Of particular interest:

  • Osteoporosis - better evaluation of bone structure and safe preventive interventions
  • Cancer - does calorie restriction provide the same protection seen in animal studies?

Please Contact: research@crsociety.org





On behalf of the Society, the investigators and millions who have already benefited, I express a heartfelt thanks to the donors who make the research possible we couldn’t do it without you!


If you haven’t already contributed to the research, consider making an investment that is priceless: Help the Society research project reveal more about slowing aging – what works and what doesn't, so that we can all put it to use. Please make a tax-deductible contribution to the Society. You may use our donation page or send your donation to the Managing Director Bob Cavanaugh at the Calorie Restriction Society, 187 Ocean Drive, Newport, NC 28570. Be sure to write "CR Research" in the memo line to avoid confusion.


Stock investors can make their stocks purchases generate considerable tax benefits by donating them to the Society.

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