The life-extending and disease-preventing benefits of calorie restriction (CR) 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 is not practical. People who want to slow aging need answers now. They need to know what works and what doesn’t, and they need a standard that can be used to evaluate any longevity intervention worth considering. This is the reason for the Calorie Restriction Society Research Project, 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 at Saint Louis Medical School. Here, Dr. Holloszy has developed a superb research laboratory that is perfect for human CR studies. Thus, the Calorie Restriction Society’s Research Project was off and running.

To provide subjects, we rallied the Calorie Restriction Society membership to participate, and we developed a method of screening participants that required proof of health status and limitation of calories. We were able to form a cohort of CRS members who had practiced CR for six or more years.

The principal investigator of the CRS Research Project is Dr. Luigi Fontana, whose passion is the science of aging. Dr. Fontana has gained special insights on human health from his experience as a practicing physician and as a researcher in metabolism. Dr. Fontana has already made medical history with the first two phases of the project by showing that calorie restriction does indeed have age-slowing effects in humans.

Dr. Fontana’s published results have attracted worldwide attention. In a study published in 2004, individuals who practiced calorie restriction showed virtually no evidence of atherosclerosis risk. Many evaluative measures, such as total cholesterol, low-density lipoprotein (LDL), triglycerides, insulin, and high sensitivity C-reactive protein were significantly lower in the CR group than in adults consuming a typical American diet. Additionally, the CR group displayed higher levels of cardio-protective high-density lipoprotein (HDL). Carotid artery wall thickness, a diagnostic indicator for coronary artery disease, was 40% less in the CR group compared with the control group. The CR group showed no evidence of plaque accumulation.1

Decline in the heart’s diastolic (relaxation) function occurs with age. In 2006, Dr. Fontana and his colleagues showed that the diastolic function of the CR cohort resembled that found in people about 15 years younger.2

Data from long-lived rodent studies shows that CR decreases serum concentrations of T(3), the thyroid hormone that mediates most of the functions of the thyroid gland. Thyroid hormones influence cell respiration, free radical production, and energy homeostasis.

A 2006 report showed that the serum level of the thyroid hormone triiodothyronine, or T(3), may be an indicator of human aging. Consistent with the studies of calorie-restricted animals, the T(3) levels of the calorie-restricted group were lower than those in the control group.3

Just this year, Drs. Fontana and Klein reviewed findings from their work and other studies to set parameters for healthy calorie restriction—essential for anyone who wishes to practice the CR lifestyle.4

Dr. Stephen R. Spindler to Lead the Genetic Testing

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 for 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 CR 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.5

Dr. Spindler and his colleagues showed in 2004 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 that is closely associated with lower cancer mortality and better health.

In findings published in 2006, 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 that CR rapidly produces beneficial effects on the heart.6