Would you like to live an extraordinarily long and healthy life – perhaps start a different career at 70 and pursue your new ambition with the same zeal you had when you were young? Or would you like to function at your peak without the significant decline that most experience as they age?

The members of the Calorie Restriction Society give a resounding Yes! to these and related questions. Inspired by hundreds of animal studies, showing that limiting calories increases lifespan and healthspan – many practice calorie restriction in hopes of living long and healthfully.

To continue to increase the knowledge of how calorie restriction can positively affect human health, the Calorie Restriction Society is providing participants, financial support, and input for what has become the first longitudinal study of calorie restriction on humans: The CRS Research Project began in 2002.

The Calorie Restriction Research Project

Luigi Fontana , M.D., Ph.D., is principal investigator of the project.

(http://geriatrics.im.wustl.edu/faculty/fontana.html).

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 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.

2.

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.

Dr. Stephen R. Spindler to lead the genetic testing

(http://www.biochemistry.ucr.edu/faculty/spindler.html)

Dr. Stephen Spindler, whose genetic analysis of calorie-restricted animals has garnered worldwide acclaim, will lead the exploration of the genetic and cell-signaling patterns of human calorie restrictors in phase three of the Calorie Restriction Project. Building on years of studying calorie restriction in animals, Dr. Spindler and his lab will provide an incisive look into how calorie restriction affects genetic expression in calorie-restricted humans.  

For those interested in finding out more about Dr. Spindler's 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

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.

Now, these great researchers will use the latest analytical methods to determine what's happening at the genetic and cell-signaling levels in human calorie restrictors. We hope that this phase three of the CR Society Research project will provide serious longevists everywhere with scientifically verified ways to evaluate anti-aging interventions.

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:

Ø     Osteoporosis: better evaluation of bone structure and safe preventive interventions

Ø     Evaluation Resveratrol as a promising CR mimetic

Ø     Cancer – does calorie restriction provide the same protection seen in animal studies?

Wishing all a very healthy long life,

Paul McGlothin, VP, Research

The Calorie Restriction Society

Research@CalorieRestriction.org

March 23, 2008