The study was published in the March 2007 issue of the Journal of American Medical Association." Research historyIn 1934, Clive McCay and Mary Crowell of Cornell University observed that laboratory rats fed a severely reduced calorie diet while maintaining vital nutrient levels resulted in life spans of up to twice as long as otherwise expected. These findings were explored in detail by a series of experiments with mice conducted by Roy Walford and his student Richard Weindruch. In 1986, Weindruch reported that restricting the calorie intake of laboratory mice proportionally increased their life span compared to a group of mice with a normal diet. The calorie-restricted mice also maintained youthful appearances and activity levels longer and showed delays in age-related diseases. The results of the many experiments by Walford and Weindruch were summarized in their book The Retardation of Aging and Disease by Dietary Restriction (1988) (ISBN 0-398-05496-7).The findings have since been accepted and generalized to a range of other animals.

Researchers are investigating the possibility of parallel physiological links in humans (see Roth et al below). In the meantime, many people have independently adopted the practice of calorie restriction in some form, hoping to achieve the expected benefits themselves. Among the most notable are the members of the Calorie Restriction Society.Trials were set up at Washington University in 2002 and involved about thirty participants. Dr. Luigi Fontana, clinical investigator, says CR practitioners seem to be aging more slowly than the rest of us. "Take systolic blood pressure," he says. "Usually, that rises with age reliably, partly because the arteries are hardening. In my group, mean age is 55, and mean systolic blood pressure is 110: that’s at the level of a 20-year-old.""Of course, I can’t tell you if my subjects will live to 130. So many uncontrollable factors affect length of life. I don’t have enough evidence to prove these people are ageing more slowly, but it looks like it.

"A study conducted by the Salk Institute for Biological Studies and published in the journal Nature in May 2007 determined that the gene PHA-4 is responsible for the longevity behind calorie restriction in animals, with similar results expected in humans. The discovery has given hope to the synthesising of future drugs to increase the human lifespan by simulating the effects of calorie restriction. However, MIT biologist Leonard Guarente cautioned that "(treatment) won't be a substitute for a healthy lifestyle. You'll still need to go to the gym". Effects of CR on different organisms PrimatesResearchers at New York's Mount Sinai School of Medicine reported in 2006 that compared to monkeys fed a normal diet, squirrel monkeys on a life-long calorie-restrictive diet were less likely to develop Alzheimer's-like changes in their brains. Since squirrel monkeys are relatively long-lived, definitive conclusions regarding whether or not they are aging slower are not yet available.

A study on rhesus macaques was started in 1989 at the University of Wisconsin-Madison. Preliminary results show lower fasting insulin and glucose levels as well as higher insulin sensitivity and LDL profiles associated with lower risk of atherogenesis in dietary restricted animals. MiceStudies in female mice have shown that estrogen receptor-alpha declines in the pre-optic hypothalamus as they age. The female mice that were given a calorically restricted diet during the majority of their lives maintained higher levels of ERa in the pre-optic hypothalamus than their non-calorically restricted counterparts. Studies in female mice have shown that both Supraoptic nucleus (SON) and Paraventricular nucleus (PVN) lose about one-third of IGF-1R immunoreactive cells with normal aging.

Low Calorie restriction

Calorie restriction, or caloric restriction (CR), aims to improve health and slow the aging process by limiting dietary energy intake. Calorie restriction is a common measure, found in several dietary regimens, including the Okinawa diet and the CRON-diet. Effects on humansIn human subjects, CR has been shown to lower cholesterol, fasting glucose, and blood pressure.citation needed Somewho? consider these to be biomarkers of aging, since there is a correlation between these markers and risk of diseases associated with aging. Except for houseflies (below), animal species tested with CR so far, including primates, rats, mice, spiders, Drosophila, C. elegans and rotifers, have shown lifespan extensioncitation needed. CR is the only known dietary measure capable of extending maximum lifespancitation needed, as opposed to average lifespan. In CR, energy intake is minimized, but sufficient quantities of vitamins, minerals and other important nutrients must be eaten.

A small-scale study in the US at the Washington University School of Medicine in St. Louis studied the effects following a calorie-restricted diet of 10-25% less calorie intake than the average Western diet. Body mass index (BMI) was significantly lower in the calorie-restricted group when compared with the matched group; 19.6 compared with 25.9. The BMI values for the comparison group are similar to the mean BMI values for middle-aged people in the US.All those on calorie-restricted diets experienced reductions in BMI after starting their diet. Their BMIs decreased from an average of 24 (range of 29.6 to 19.4) to an average of 19.5 (range of 22.8 to 16.5) over the course of their dieting (3-15 years). Nearly all the decrease in BMI occurred in the first year of dieting. It was found that the average total cholesterol and LDL (bad) cholesterol levels for calorie-restricted individuals were the equivalent of those found in the lowest 10% of normal people in their age group. It was found that the average HDL (good) cholesterol levels for calorie-restricted individuals were very high—in the 85th to 90th percentile range for normal middle-aged US men.

These positive changes in calorie-restricted individuals were found to occur mainly in the first year of dieting. It was found that the calorie-restricted group had remarkably low triglyceride levels. In fact, they were as low as the lowest 5% of Americans in their 20s. This is more remarkable when it is noted that the calorie-restricted individuals were actually aged between 35 and 82 years. Both systolic and diastolic blood pressure levels in calorie-restricted group were remarkably low, about 100/60, values normally found in 10-year-old children. Fasting plasma insulin concentration was 65% lower and fasting plasma glucose concentration was also significantly lower in the calorie-restricted group when compared with the comparison group." The comparison group's statistics aligned approximately with the US national average on the dimensions considered. Fasting plasma insulin levels and fasting plasma glucose levels are used as tests to predict diabetes. "The researchers also found that excessive calorie restriction causes malnutrition and can lead to anemia, muscle wasting, weakness, dizziness, lethargy, fatigue, nausea, diarrhea, constipation, gallstones, irritability and depression.