X-Message-Number: 31386 Date: Sat, 14 Feb 2009 10:14:03 -0800 (PST) From: Subject: Caloric Restriction May Benefit Only Obese Mice http://www.sciencedaily.com/releases/2009/01/090123101224.htm Eating Less May Not Extend Human Life: Caloric Restriction May Benefit Only Obese Mice ScienceDaily (Jan. 26, 2009) - If you are a mouse on the chubby side, then eating less may help you live longer. For lean mice - and possibly for lean humans, the authors of a new study predict - the anti-aging strategy known as caloric restriction may be a pointless, frustrating and even dangerous exercise. "Today there are a lot of very healthy people who look like skeletons because they bought into this," said Raj Sohal, professor at the University of Southern California's School of Pharmacy. He and Michael Forster, of the University of North Texas Health Science Center, compared the life span and caloric intake of two genetically engineered strains of mice. The "fat" strain, known as C57BL/6, roughly doubles in weight over its adult life. That strain benefited from caloric restriction, Sohal said. The "lean" strain, DBA/2, does not become obese. Caloric restriction did not extend the life of these mice, confirming previous work by Forster and Sohal. "Our study questions the paradigm that caloric restriction is universally beneficial," Sohal said. "Contrary to what is widely believed, caloric restriction does not extend (the) life span of all strains of mice." By measuring the animals' metabolic rate, Sohal and his colleagues came to a deceptively simple conclusion: Caloric restriction is only useful when, as in the case of the obese mice, an animal eats more than it can burn off. "Your energy expenditure and your energy intake should be in balance," Sohal said. "It's as simple as that. And how do you know that? By gain or loss of weight. "The whole thing is very commonsensical." For humans of normal weight, Sohal strongly cautions against caloric restriction. In a 2003 study, he and Forster found that caloric restriction begun in older mice - both in DBA and leaner C57 individuals - actually shortened life span. However, Sohal said that obese individuals are probably better off cutting calories than increasing their exercise to make up for overeating. Overly vigorous exercise can lead to injuries and long-term wear and tear. In other words, it is better to skip the double cheeseburger than to turn up the treadmill after binging at Carl's Jr. Sohal's study is not the first to question the allegedly universal benefits of caloric restriction. A study by Ross et al. published in Nature in 1976 ("Dietary practices and growth responses as predictors of longevity") found that caloric restriction works best in mice that gain weight rapidly in early adulthood, Sohal said. Studies of caloric restriction in wild types of mouse strains have shown minimal life span extension, he added. Next, the researchers want to understand why the obese mice have a lower metabolic rate that promotes weight gain. The other members of the research team were Melissa Ferguson and Barbara Sohal of the USC School of Pharmacy. Funding for the study came from the National Institute on Aging, part of the National Institutes of Health. Journal reference: 1. Sohal et al. Life Span Extension in Mice by Food Restriction Depends on an Energy Imbalance. Journal of Nutrition, Jan 2009; DOI: 10.3945/jn.108.100313 Adapted from materials provided by University of Southern California, via EurekAlert!, a service of AAAS. J Nutr. 2009 Jan 13. [Epub ahead of print] Life Span Extension in Mice by Food Restriction Depends on an Energy Imbalance. Sohal RS, Ferguson M, Sohal BH, Forster MJ. Department of Pharmacology and Pharmaceutical Sciences, University of Southern California, Los Angeles, CA 90089. In this study, our main objective was to determine whether energy restriction (ER) affects the rate of oxygen consumption of mice transiently or lastingly and whether metabolic rate plays a role in the ER-related extension of life span. We compared rates of resting oxygen consumption between C57BL/6 mice, whose life span is prolonged by ER, and the DBA/2 mice where it is not, at 6 and 23 mo of age, following 40% ER for 2 and 19 mo, respectively. Mice of the 2 strains that consumed food ad libitum (AL) had a similar body mass at the age of 4 mo and consumed similar amounts of food throughout the experiment; however, the body weight subsequently significantly increased (20%) in the C57BL/6 mice but did not increase significantly in the DBA/2 mice. The resting rate of oxygen consumption was normalized as per g body weight, lean body mass, organ weight, and per mouse. The resting rate of oxygen consumption at 6 mo was significantly higher in AL DBA/2 mice than the AL C57BL/6 mice for all of the criteria except organ weight. A similar difference in AL mice of the 2 strains was present at 23 mo when resting oxygen consumption was normalized to body weight. Resting oxygen consumption was lowered by ER in both age groups of each strain according to all 4 criteria used for normalization, except body weight in the C57BL/6 mice. The effect of ER on resting oxygen consumption was thus neither transient nor age or strain dependent. Our results suggest that ER-induced extension of life span occurs in the mouse genotype in which there is a positive imbalance between energy intake and energy expenditure. PMID: 19141702 Rate This Message: http://www.cryonet.org/cgi-bin/rate.cgi?msg=31386