The effects of different levels of dietary restriction on aging and survival in the Sprague-Dawley rat: Implications for chronic studies

Guo

J Cereb Blood Flow Metab

et al. 2013

Dietary restriction (DR) protects against neuronal dysfunction and degeneration, and reduces the risk of ischemic stroke. This study examined the role of silent information regulator T1 (SIRT1) and arterial baroreflex in the beneficial effects of DR against stroke, using two distinct stroke models: stroke-prone spontaneously hypertensive rats (SP-SHRs) and Sprague-Dawley (SD) rats with middle cerebral artery occlusion (MCAO). Sirt1 knockout (KO) mice were used to examine the involvement of sirt1. Sinoaortic denervation was used to inactivate arterial baroreflex. Dietary restriction was defined as 40% reduction of dietary intake. Briefly, DR prolonged the life span of SP-SHRs and reduced the infarct size induced by MCAO. Dietary restriction also improved the function arterial baroreflex, decreased the release of proinflammatory cytokines, and reduced end-organ damage. The beneficial effect of DR on stroke was markedly attenuated by blunting arterial baroreflex. Lastly, the infarct area in sirt1 KO mice was significantly larger than in the wild-type mice. However, the beneficial effect of DR against ischemic injury was still apparent in sirt1 KO mice. Accordingly, arterial baroreflex, but not sirt1, is important in the protective effect of DR against stroke.

Section: Discussionsupporting

confidence: 61%

Involvement of Arterial Baroreflex in the Protective Effect of Dietary Restriction Against Stroke

Guo

J Cereb Blood Flow Metab

et al. 2013

“…In addition, the USA Food and Drug AdministraEffects of reduced food intake on toxicity study parameters in rats Tomoyuki Moriyama, Shigeharu Tsujioka, Takashi Ohira, Satoko Nonaka, Hisataka Ikeda, Hiroki Sugiura, Masayuki Tomohiro, Keiji Samura and Masaru Nishikibe tion (FDA) (Allaben et al, 1996;Duffy et al, 2001) and the Society of Toxicologic Pathology (Nold et al, 2001) have stated that dietary optimization is needed in rodent bioassays. We have been conducting toxicity studies in the dietary-optimized rat model, and frequently faced the dilemma of whether the observed changes were a direct effect of drug or secondary to decreased food intake.…”

Section: Introductionmentioning

confidence: 99%

Effects of reduced food intake on toxicity study parameters in rats

Moriyama¹,

Tsujioka²,

Ohira³

et al. 2008

J. Toxicol. Sci.

-This study comprehensively describes the effects of various levels of food reduction on a wide range of toxicological parameters in dietary-optimized rats (fed with approximately 75% of ad libitum food consumption daily; 16 g and 22 g/day for females and males, respectively) that has been established as a nutritionally appropriate and well-controlled animal model in conducting toxicity studies. Toxicological parameters, including general condition, ophthalmology, clinical pathology and anatomic pathology, were examined in dietary-optimized Crl:CD(SD) female and male rats fed 16 g and 22 g/day (control), 12 g and 17 g/day (75% group), 8 g and 11 g/day (50% group), or 4 g and 6 g/day (25% group), respectively for 2 weeks. There was mortality and morbidity including reddish urine in 25% -cular hemolysis induced by severe food reduction. Hemoconcentration, decreased leukocytes and platelets, decreases in nutritional elements (serum glucose, protein, and lipids), increased aspartate aminotransferase and alanine aminotransferase, imbalanced electrolytes, and/or decreased urinary pH were observed in all restriction groups. Histopathologically remarkable changes included erythrophagocytosis in the spleen/liver and renal tubular necrosis with hyaline cast/droplets in 25% group; in addition to bone marrow depletion, lymphoid depletion in thymus/spleen/lymph node, and/or decreased secretion in the prostate/seminal vesicle in all restriction groups. Most of these changes were considered attributable to nutrifood reduction. These results will enable toxicologists to help distinguish primary drug-induced effects from secondary changes associated with decreases in food consumption.

“…Calorie restriction (CR), also known as dietary restriction, food restriction and energy restriction, is referred to as the regimen of inducing under-nutrition without malnutrition by reducing food intake 10%~40% below the ad libitum level (Duffy et al 2001). It is a simple and reproducible method widely used in research for delaying the aging process, extending average or maximum lifespan and preventing the onset of aging-related diseases such as diabetes, obesity, cancer, hypertension, cardiovascular diseases, heart failure and so on (Xiang and He 2011).…”

mentioning

confidence: 99%

Calorie Restriction from a Young Age Preserves the Functions of Pancreatic β Cells in Aging Rats

Zhao

et al. 2012

Tohoku J. Exp. Med.

Calorie restriction (CR) is a simple method for delaying aging process, extending lifespan, and preventing the onset of aging-related diseases, such as diabetes. However, the mechanism, by which CR influences β-cell functions during the aging process, still remains unclear. In this study, sixteen 8-week-old male Sprague-Dawley rats were randomized to control group with food intake ad libitum and CR group fed with 70% of food intake of the control group. Twenty-four weeks later, the body weights of the rats with CR were significantly lower with the smaller amounts of perirenal and epididymal fats, compared to those of control rats. The β-cell activity, as judged by the early insulin secretion in the intraperitoneal glucose tolerance test, was significantly higher in the CR group than that in control animals. Moreover, CR animals showed the increased β-cell mass and proliferation of β-cells in pancreas. The plasma level of malondialdehyde was lower in CR rats than that in control rats, while the activities of superoxide dismutase, catalase and glutathione peroxidase in plasma were higher in CR rats than control rats. These results indicate that aging is associated with the increases in oxidative stress, which was, however, alleviated by CR. In conclusion, CR from a young age preserves the principal β-cell function of early insulin secretion in rats probably by stimulating the β-cell proliferation. Our observations provide the evidence for clinical significance of CR in preventing β-cell dysfunction during the aging process, which may delay the onset of aging-related disease, including diabetes in humans.