Calorie Restriction in Biosphere 2: Alterations in Physiologic, Hematologic, Hormonal, and Biochemical Parameters in Humans Restricted for a 2-Year Period

R. L. Walford, D. Mock, R. Verdery, T. MacCallum
2002 The journals of gerontology. Series A, Biological sciences and medical sciences  
Four female and four male crew members, including two of the present authors (R. Walford and T. MacCallum)-seven of the crew being ages 27 to 42 years, and one aged 67 years-were sealed inside Biosphere 2 for two years. During seven eighths of that period they consumed a low-calorie (1750-2100 kcal/d) nutrient-dense diet of vegetables, fruits, nuts, grains, and legumes, with small amounts of dairy, eggs, and meat ( ‫ف‬ 12% calories from protein, ‫ف‬ 11% from fat, and ‫ف‬ 77% from complex
more » ... drates). They experienced a marked and sustained weight loss of 17 Ϯ 5%, mostly in the first 8 months. Blood was drawn before entry into Biosphere 2, at many time-points inside it, and four times during the 30 months following exit from it and return to an ad libitum diet. Longitudinal studies of 50 variables on each crew member compared outside and inside values by means of a Bayesian statistical analysis. The data show that physiologic (e.g., body mass index, with a decrease of 19% for men and 13% for women; blood pressure, with a systolic decrease of 25% and a diastolic decrease of 22%), hematologic (e.g., white blood cell count, decreased 31%), hormonal (e.g., insulin, decreased 42%; T3, decreased 19%), biochemical (e.g., blood sugar, decreased 21%; cholesterol, decreased 30%), and a number of additional changes, including values for rT3, cortisol, glycated hemaglobin, plus others, resembled those of rodents or monkeys maintained on a calorie-restricted regime. Significant variations in several substances not hitherto studied in calorie-restricted animals are also reported (e.g., androstenedione, thyroid binding globulin, renin, and transferrin). We conclude that healthy nonobese humans on a low-calorie, nutrient-dense diet show physiologic, hematologic, hormonal, and biochemical changes resembling those of rodents and monkeys on such diets. With regard to the health of humans on such a diet, we observed that despite the selective restriction in calories and marked weight loss, all crew members remained in excellent health and sustained a high level of physical and mental activity throughout the entire 2 years. IOSPHERE 2 is a 3.15 acre, 7-million ft 3 (0.6-million m 3 ) closed ecological space near Tucson, Arizona. At the time of the present study it contained five wilderness and two domestic biomes (rain forest, savannah, desert, ocean, marsh, agricultural station, and living quarters), plus a large basement "technosphere." It could be likened to an aircraft carrier with a massive garden on top and extensive mechanical innards below decks. The entire complex rests on a 3/8in ( ‫ف‬ 0.9 cm) thick stainless-steel plate. In September 1991, four men and four women entered Biosphere 2 and the complex was physically sealed ("closure") for 2 years. Thermodynamically it remained open in that sunlight and electric power entered, heat was removed by a sealed water-conduction system, and electronic information was transferred. Except for specific instances using an air lock and limited to scientific items, no material entered or left for the 2-year period, except that, for reasons given elsewhere (1), oxygen had to be supplied on two occasions. All organic material was recycled or stored as "carbon banks," all water and virtually all air was recycled, and ‫ف‬ 85% of food was raised inside (the rest coming from preentry back-up stores). As much as possible, Biosphere 2 was intended to be a completely closed, self-sustaining ecological system requiring only adaptive management by the crew members (1,2). Before closure a daily intake in excess of 2500 kcal per person had been projected, to be supplied entirely by the agricultural system. In the actual event, however, as a result of crop problems, caloric intake during the first 6 months averaged only 1784 kcal/day, rising then to ‫ف‬ 2000 kcal for most of the remaining time period. This intake was low in relation to the large amount of physical labor required of the crew members. All crew members lost significant amounts of weight over the first 6-8 months ( ‫ف‬ 21% for the men, B
doi:10.1093/gerona/57.6.b211 pmid:12023257 fatcat:3r6zhzd7afeivbn5r554ht6nyq