Caloric restriction
Intentional weight loss reduces mortality rate in a rodent model of dietary obesity.
Obes Res. 2005 Apr;13(4):693-702.
Vasselli JR, Weindruch R, Heymsfield SB, Pi-Sunyer FX, Boozer CN, Yi N, Wang C, Pietrobelli A, Allison DB.
Department of Biostatistics, University of Alabama, Ryals Public Health Building, University Boulevard, Birmingham
OBJECTIVE: We used a rodent model of dietary obesity to evaluate effects of caloric restriction-induced weight loss on mortality rate. Research Measures and Procedures: In a randomized parallel-groups design, 312 outbred Sprague-Dawley rats (one-half males) were assigned at age 10 weeks to one of three diets: low fat (LF; 18.7% calories as fat) with caloric intake adjusted to maintain body weight 10% below that for ad libitum (AL)-fed rat food, high fat (HF; 45% calories as fat) fed at the same level, or HF fed AL. At age 46 weeks, the lightest one-third of the AL group was discarded to ensure a more obese group; the remaining animals were randomly assigned to one of three diets: HF-AL, HF with energy restricted to produce body weights of animals restricted on the HF diet throughout life, or LF with energy restricted to produce the body weights of animals restricted on the LF diet throughout life. Life span, body weight, and leptin levels were measured. RESULTS: Animals restricted throughout life lived the longest (p < 0.001). Life span was not different among animals that had been obese and then lost weight and animals that had been nonobese throughout life (p = 0.18). Animals that were obese and lost weight lived substantially longer than animals that remained obese throughout life (p = 0.002). Diet composition had no effect on life span (p = 0.52). DISCUSSION: Weight loss after the onset of obesity during adulthood leads to a substantial increase in longevity in rats.
Toward a unified theory of caloric restriction and longevity regulation.
Mech Ageing Dev. 2005 May 10
Sinclair DA.
Department of Pathology, Harvard Medical School, 77 Avenue Louis Paster, Boston, MA 02115, USA.
The diet known as calorie restriction (CR) is the most reproducible way to extend the lifespan of mammals. Many of the early hypotheses to explain this effect were based on it being a passive alteration in metabolism. Yet, recent data from yeast, worms, flies, and mammals support the idea that CR is not simply a passive effect but an active, highly conserved stress response that evolved early in life's history to increase an organism's chance of surviving adversity. This perspective updates the evidence for and against the various hypotheses of CR, and concludes that many of them can be synthesized into a single, unifying hypothesis. This has important implications for how we might develop novel medicines that can harness these newly discovered innate mechanisms of disease resistance and survival.
Long-term caloric restriction increases UCP3 content but decreases proton leak and reactive oxygen species production in rat skeletal muscle mitochondria.
Am J Physiol Endocrinol Metab. 2005 May 10
Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME.
Biochemistry, Microbiology and Immunology, University of Ottawa, Ottawa, ON, Canada.
Calorie restriction (CR) without malnutrition increases lifespan and delays the onset of a variety of diseases in a wide range of animal species. However, the mechanisms responsible for the retardation of aging with CR are poorly understood. We proposed that CR may act, in part, by inducing a hypometabolic state characterized by decreased reactive oxygen species (ROS) production and mitochondrial proton leak. Here we examine the effects of long-term CR on whole animal energetics as well as muscle mitochondrial energetics, ROS production and ROS damage. CR was initiated in male FBNF1 rats at 6 months of age and continued for 12 or 18 months. Mean whole body oxygen consumption was 34.6% (P<0.01) and 35.6% (P<0.001) lower in CR rats than in controls after 12 and 18 months CR, respectively. Body mass-adjusted oxygen consumption was 11.1% and 29.5 % lower (both P<0.05) in the CR rats than in controls after 12 and 18 month CR. Muscle mitochondrial leak-dependent (state 4) respiration was decreased after 12 months compared to controls; however, following 18 months of CR there were slight but not statistically significant differences. Proton leak kinetics were affected by 12 months CR such that leak-dependent respiration was lower in CR mitochondria only at protonmotive force values exceeding 170mV. Mitochondrial H2O2 production and oxidative damage were decreased by CR at both time points and increased with age. Muscle UCP3 protein content increased with long-term CR, consistent with a role in protection from ROS, but inconsistent with the observed decrease or no change in proton leak.
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