Caloric restriction
Intentional weight loss reduces mortality rate in a rodent model of dietary obesity. 1222222Obes Res. 2005 Apr;13(4):693-702.
2222222 Vasselli JR, Weindruch R, Heymsfield SB, Pi-Sunyer FX, Boozer CN, Yi N, Wang C, Pietrobelli A, Allison DB.
2222222 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.
1222222Mech Ageing Dev. 2005 May 10
1222222 Sinclair DA.
1222222 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.
1222222Am J Physiol Endocrinol Metab. 2005 May 10
1222222 Bevilacqua L, Ramsey JJ, Hagopian K, Weindruch R, Harper ME.
1222222 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 kinethttp://antiaging-europe.com/admin/ics 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.
Thirty percent calorie reduction improves verbal memory by 20 percent.
2222222PNAS. 2009 December 19
2222222A. V. Witte, M. Fobker, R. Gellner, S. Knecht, A. Flöel. 2222222The Salk Institute, San Diego, CA. Reducing calorie intake by 30 percent improves memory in elderly individuals, according to research published online Jan. 26 in the Proceedings of the National Academy of Sciences. To determine whether the observed beneficial effects of diet on cognitive function in animals could be extended to elderly humans, A.V. Witte, and colleagues from the University of Munster in Germany assigned 50 healthy, normal to overweight elderly individuals (mean age 60.5 years, mean body mass index, 28 kg/m2) to one of three groups: a diet containing 30 percent fewer calories; a diet containing a 20 percent increase in unsaturated fatty acids (keeping total fat constant); or no change in diet. After three months, the researchers found that only caloric restriction was associated with a significant increase (mean, 20 percent) in verbal memory scores. This was correlated with reductions in fasting plasma insulin levels and high sensitive C-reactive protein, with no changes in the levels of brain-derived neurotrophic factor, the author note. "This interventional trial demonstrates beneficial effects of caloric restriction on memory performance in healthy elderly subjects," Witte and colleagues conclude. "Mechanisms underlying this improvement might include higher synaptic plasticity and stimulation of neurofacilitatory pathways in the brain because of improved insulin sensitivity and reduced inflammatory activity.
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