2005

Nat Rev Mol Cell Biol. 2005 Apr;6(4):298-305.
Calorie restriction, SIRT1 and metabolism: understanding longevity.
Bordone L, Guarente L.
Department of Biology, Massachusetts Institute of Technology, Cambridge, Massachusetts 02139, USA.

Calorie restriction (CR) is the only experimental manipulation that is known to extend the lifespan of a number of organisms including yeast, worms, flies, rodents and perhaps non-human primates. In addition, CR has been shown to reduce the incidence of age-related disorders (for example, diabetes, cancer and cardiovascular disorders) in mammals. The mechanisms through which this occurs have been unclear. CR induces metabolic changes, improves insulin sensitivity and alters neuroendocrine function in animals. In this review, we summarize recent findings that are beginning to clarify the mechanisms by which CR results in longevity and robust health, which might open new avenues of therapy for diseases of ageing.

J Nutr. 2005 Jun;135(6):1343-6.
Microarray evaluation of dietary restriction.
Han ES, Hickey M.
Department of Biological Science, University of Tulsa, Tulsa, OK 74104.

Dietary restriction (DR) extends the life span and retards many age-related cellular and molecular changes in laboratory rodents. However, neither its underlying mechanism nor the limits of its action are fully understood. In this review, we assessed the effect of DR on gene expression in vertebrate and invertebrate animals using data generated by microarrays. Altered genes in DR mice reported in 15 articles published since 1999 were compared. A comparison of altered genes by DR in mice, rats, pigs, monkeys, yeast, and flies showed no common gene altered by DR among different species. It seems that individual genes altered in the expression by DR were constrained within species. When we compared the functions of altered genes across all species, we found that certain functions such as metabolism, energy metabolism, stress and immune response, cell growth, and transcription regulation were shared among species. Although individual genes seem to be affected by DR differently among species, the overall physiologic influence of DR may be similar.

1999

Am J Clin Nutr 1999 Jan;69(1):13-7
Changes in resting energy expenditure after weight loss in obese African American and white women.
Foster GD, Wadden TA, Swain RM, Anderson DA, Vogt RA.
University of Pennsylvania School of Medicine, Philadelphia 19104-2648, USA.

BACKGROUND: Previous studies showed that resting energy expenditure (REE) is lower in obese African American women than in obese white women. It is unknown, however, whether there are racial differences in how REE responds to weight loss and energy restriction. OBJECTIVE: We assessed REE, body composition, and respiratory quotient before and after weight loss in obese black and white women. DESIGN: We measured REE by indirect calorimetry and body composition by densitometry before and after 20-24 wk of treatment with a 3870-4289-kJ/d diet. Subjects were 109 obese females (24 black, 85 white) with a mean (+/-SD) body mass index (in kg/m2) of 36.3+/-5.0, weight of 95.7+/-12.6 kg, and age of 42.3+/-8.1 y. RESULTS: Before treatment, REE, adjusted for body composition, was significantly lower in black than in white subjects (P = 0.001). Black subjects lost significantly less weight during treatment than did white subjects (13.4+/-5.9 kg or 14.2+/-5.7% compared with 16.4+/-5.6 kg or 17.0+/-5.7%, respectively; P = 0.04). Analyses that controlled for initial REE and changes in fat mass and fat-free mass showed that blacks had significantly greater decreases in REE after treatment than did whites (9.9+/-7.3% compared with 6.3+/-7.4%; P = 0.02). CONCLUSION: This study suggests that weight loss results in greater reductions in REE in obese black women than in obese white women. These data underscore the need to consider both biological and behavioral factors when setting expectations and assessing outcomes for obesity treatment in African American women.

J Gerontol A Biol Sci Med Sci 1999 Jan;54(1):B5-11; discussion B12-3
Long-term calorie restriction reduces energy expenditure in aging monkeys.
DeLany JP, Hansen BC, Bodkin NL, Hannah J, Bray GA.
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.delanyjp@mhs.pbrc.edu

Calorie restriction to produce stable long-term adult body weight for approximately 10 years prevents obesity and diabetes in middle-aged rhesus monkeys. To determine whether this dietary regimen also alters energy metabolism, the doubly labeled water method was used to measure total daily energy expenditure. Six adult male rhesus monkeys, which had been calorie-restricted for more than 10 years, were compared to 8 control adult monkeys, which had been fed ad libitum for their entire lives. The calorie-restricted monkeys weighed less than the ad-libitum fed monkeys and had a lower lean body mass and lower fat mass. Total daily energy expenditure was lower in the calorie-restricted than in the ad-libitum fed monkeys, even when corrected for differences in body size using body weight (563 +/- 64 vs 780 +/- 53 kcal/d; p < .04), surface area (547 +/- 67 vs 793 +/- 56 kcal/d; p < .05), or lean body mass (535 +/- 66 vs 801 +/- 54 kcal/d; p < .02) as covariates. Thyroxine (T4) was reduced and the free thyroxine index was suggestively lower in the calorie-restricted monkeys whereas triiodothyronine (T3) was not significantly different. Activity in calorie-restricted monkeys was similar to that of a weight-matched younger adult comparison group. We conclude that the process of preventing obesity by long-term caloric restriction causes a significant and sustained long-term reduction in energy expenditure, even when corrected for lean body mass.

1994

Am J Clin Nutr 1994 Jul;60(1):29-36
Fuel and energy metabolism in fasting humans.
Carlson MG; Snead WL; Campbell PJ
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN 37232-2230.

ABSTRACT: Fuel and energy homeostasis was examined in six male volunteers during a 60-h fast by using a combination of isotopic tracer techniques ([3-3H]glucose, [2H5]glycerol, [1-14C]palmitate, and L-[1-13C]leucine) and indirect calorimetry. Plasma glucose concentration and hepatic glucose production decreased by 30% with fasting (5.2 +/- 0.1 to 3.8 +/- 0.2 mmol/L and 11.8 +/- 0.5 to 8.2 +/- 0.6 mumol.kg-1.min-1, respectively, both P < 0.001) and glucose oxidation declined approximately 85% (P < 0.01). Lipolysis and primary (intraadipocyte) free fatty acid (FFA) reesterification increased 2.5-fold (1.7 +/- 0.2 to 4.2 +/- 0.2 mumol.kg-1.min-1 and 1.5 +/- 0.4 to 4.2 +/- 0.8 mumol.kg-1.min-1, respectively, both P < 0.05). This provided substrate for the increase in fat oxidation (from 2.7 +/- 0.3 to 4.3 +/- 0.1 mumol.kg-1.min-1, P < 0.01), which contributed approximately 75% of resting energy requirements after the 60-h fast and increased the supply of glycerol for gluconeogenesis. Proteolysis and protein oxidation increased approximately 50% during fasting (P < 0.01 and P < 0.05, respectively). We conclude that the increase in FFA reesterification with fasting modulates FFA availability for oxidation and maximizes release of glycerol from triglyceride for gluconeogenesis.