Longevity Research Program
Director: John O. Holloszy, M.D.
Co-Director: Luigi Fontana, M.D. Ph.D.
Project Summary
To determine whether intermittent fasting (IF) 2 days/week induces the same beneficial anti-aging and health benefits as CR in middle-aged men and women with BMI’s in the 24 to 35 kg/m2 range.
Specifically, the research seeks to determine the effects fasting for 2 days per week on:
- Chronic low level inflammation as reflected in measurements of hsC-reactive Protein (hs-CRP), IL6, TNFα and prostaglandin E2 in plasma, and down-regulation of expression of genes encoding NF-kB, inflammatory cytokines, and factors that mediate fibrosis measured in distal colon mucosa biopsies.
- Concentrations of insulin, IGF-1, IGFBP3, testosterone, estradiol, sex hormone binding globulin, leptin, adiponecten, T3 and TSH in plasma, and the insulin/IGF-1 pathway in colon mucosa biopsies.
- Glucose tolerance and lipid profile.
- Cardiac elasticity by measurement of cardiac diastolic function by Doppler echocardiography.
- Aortic elasticity using pulse wave velocity measurement.
- Body weight, waist circumference and body composition measured by DEXA.
- Intima-media thickness of the common carotid arteries measured using echodoppler.
- Protein carbonyls in plasma as a marker of oxidative damage.
- DNA methylation in skeletal muscle and colon mucosa biopsies as a marker of biological age.
Progress Report:
We will enroll 40 participants in the 30 to 65 years of age range with the goal of having equal numbers of women and men with BMIs in the high normal to moderately obese range (25 to 35 kg/m2). They will be eating usual U.S. diets and sedentary to moderately active (i.e., not exercise trained).
Exclusion criteria include any chronic disease that could interfere with interpretation of results, pregnancy, smoking, alcoholism, psychiatric problems, and life situations that would interfere with study participation.
The study will be randomized and controlled, with the controls crossing over to the Fasting group after 6 months so that they can benefit from participation in the study. The duration of the IF will be 12 mo for the group assigned to IF initially, and 6 months for the controls, who will stay on their usual diets for the first 6 months.
After screening by physical examination and blood tests, the participants will meet with the study dietician to design their weekly meals plans and menus for the non-fasting days. The IF will consist of fasting two non-consecutive days per week. Participants are asked to skip breakfast, lunch, dinner, snacks and calorie-containing drinks on the fast days but will have the option to eat a salad consisting of non-starchy vegetables dressed with 2 tablespoons of salad dressing consisting of vegetable oil, with vinegar and seasonings. Weight will be monitored weekly and advice and support provided by the study dietician and investigators. The effects of the IF will be evaluated.
