Expression of Longevity Genes in Response to Extended Fasting

The purpose of this study is to evaluate the effect of fasting on physical changes associated with cardiovascular disease.

Coronary heart disease (CHD) is the largest contributor to morbidity and mortality in the Western world and is associated with high-calorie diet, high body mass, and a variety of other factors. CHD can lead to myocardial infarction (MI) and other embolic events. A growing body of evidence suggests that relatively low caloric intake in the diets of a variety of animals increases longevity and preliminary evidence among humans indicates that such caloric restriction reduces risk factors for CHD, including cholesterol levels, blood pressure, glucose, and obesity. Caloric restriction has also been shown to alter the expression of certain genes, especially the forkhead box (FOX) O and sirtuin (SIRT) genes whose over-expression has been shown to increase longevity in animal models. Extended avoidance of caloric intake, also called fasting or short-term starvation, has been shown to increase expression of the FOXA genes that have similar sequence and function as the FOXO genes and that have been shown to increase longevity among animals regardless of FOXO function. We recently demonstrated that the risk of CHD was significantly lower among patients who reported a history of routine periodic extended fasting. The two primary hypotheses for this observation are that fasting may improve individual ability to control dietary intake or that fasting may initiate a cascade of protective mechanisms that preserve cellular and metabolic health.

Eligibility Criteria:
Inclusion Criteria:

1. The volunteer (male or non-pregnant female, any ethnicity) must be \>18 years of age.
2. The volunteer must either have a body mass index of 25.0-35.0 kg/m2 or the combination of a body mass index of 18.5-24.9 kg/m2 and two or more previously or currently measured symptoms of the metabolic syndrome (fasting glucose≥110 mg/dL, triglycerides≥150 mg/dL, high-density lipoprotein cholesterol\<40 mg/dL in males or \<50 mg/dL in females, systolic blood pressure≥130 mmHg or diastolic blood pressure≥85 mmHg, or waist circumference≥40 inches in males or ≥36 inches in females \[glucose and cholesterol levels may be self-reported\]).
3. The volunteer has not routinely participated in caloric restriction (deliberate limitation of caloric intake of \<80% than the FDA-recommended daily caloric intake) within the last 2 years, has not participated in extended fasting (\>12 hours at a time) for at least a year, and does not deliberately skip meals as a routine dietary practice.

Exclusion Criteria:

1. Body mass index \<18.5 or \>35 kg/m2.
2. Current active cancer treatment, treatment with immunosuppressive medications, or solid organ transplantation within 1 year.
3. Presence of immunosuppressive disease, myocardial infarction, peripheral vascular disease, or stroke within the past year.
4. Use of insulin.
5. Although it is unlikely fasting will harm the pregnant or lactating woman, the dietary restrictions placed on the participant for the duration of the study may conflict with dietary recommendations for pregnant or lactating women. Women of child bearing potential, therefore, will meet an exclusion if they become pregnant.