Weindruch, R. & Sohal, R. S. Seminars in medicine of the Beth Israel Deaconess Medical Center. Caloric intake and aging. N. Engl. J. Med. 337, 986-994

Department of Medicine and Veterans Affairs Geriatric Research, Education, and Clinical Center, University of Wisconsin, Madison 53705, USA.
New England Journal of Medicine (Impact Factor: 55.87). 11/1997; 337(14):986-94. DOI: 10.1056/NEJM199710023371407
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Available from: Rajindar S Sohal
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    • "Caloric restriction (CR) is a dietary regimen, which improves health and slows the aging process in evolutionarily distant organisms by limiting dietary energy intake [123]. There is increasing epidemiological and experimental evidence that CR plays an important role in vasoprotection in aging and in pathological conditions associated with accelerated vascular aging [124]. "
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    ABSTRACT: Age is an independent risk factor of cardiovascular disease, even in the absence of other traditional factors. Emerging evidence in experimental animal and human models has emphasized a central role for two main mechanisms of age-related cardiovascular disease: oxidative stress and inflammation. Excess reactive oxygen species (ROS) and superoxide generated by oxidative stress and low-grade inflammation accompanying aging recapitulate age-related cardiovascular dysfunction, that is, left ventricular hypertrophy, fibrosis, and diastolic dysfunction in the heart as well as endothelial dysfunction, reduced vascular elasticity, and increased vascular stiffness. We describe the signaling involved in these two main mechanisms that include the factors NF-κB, JunD, p66Shc, and Nrf2. Potential therapeutic strategies to improve the cardiovascular function with aging are discussed, with a focus on calorie restriction, SIRT1, and resveratrol.
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    • "Using this assay, studies have demonstrated interventions, genetic and otherwise, that regulate lifespan not only in yeast, but also in higher organisms, including mammals. For example, calorie restriction (CR) extends yeast chronological lifespan and has been shown to increase lifespan by up to 40% in mice, while impairment of the conserved insulin/IGF-1-like and TOR pathways produces similar gains in both organisms [7], [8], [16], [17]. The second model system, the replicative lifespan of mammalian cells in culture, reflects the propensity of cells to senesce in vivo due to the accumulation of genotoxic damage, as well as other types of cellular stress. "
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    ABSTRACT: A methionine-restricted diet robustly improves healthspan in key model organisms. For example, methionine restriction reduces age-related pathologies and extends lifespan up to 45% in rodents. However, the mechanisms underlying these benefits remain largely unknown. We tested whether the yeast chronological aging assay could model the benefits of methionine restriction, and found that this intervention extends lifespan when enforced by either dietary or genetic approaches, and furthermore, that the observed lifespan extension is due primarily to reduced acid accumulation. In addition, methionine restriction-induced lifespan extension requires the activity of the retrograde response, which regulates nuclear gene expression in response to changes in mitochondrial function. Consistent with an involvement of stress-responsive retrograde signaling, we also found that methionine-restricted yeast are more stress tolerant than control cells. Prompted by these findings in yeast, we tested the effects of genetic methionine restriction on the stress tolerance and replicative lifespans of cultured mouse and human fibroblasts. We found that such methionine-restricted mammalian cells are resistant to numerous cytotoxic stresses, and are substantially longer-lived than control cells. In addition, similar to yeast, the extended lifespan of methionine-restricted mammalian cells is associated with NFκB-mediated retrograde signaling. Overall, our data suggest that improved stress tolerance and extension of replicative lifespan may contribute to the improved healthspan observed in methionine-restricted rodents, and also support the possibility that manipulation of the pathways engaged by methionine restriction may improve healthspan in humans.
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    • "where " Na " represents the number of mitochondria per μm 2 of cell and k and β the mitochondrial size distribution and shape coefficient, respectively . These coefficients were calculated using the results of planimetric measurements and assimilating mitochondrial shape to regular prolate spheroids (Weibel, 1979). Planimetric measurements on mitochondria were performed using ImageJ software (N.I.H.). "
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    ABSTRACT: In this paper we analyzed changes in hepatocyte mitochondrial mass and ultrastructureas well as in mitochondrial markers of fission/fusion and biogenesis in mice subjected to 40% calorie restriction (CR) for 18 months versus ad libitum-fed controls. Animals subjected to CR were separated into three groups with different dietary fat: soybean oil (also in controls), fish oil and lard. Therefore, the effect of the dietary fat under CRwas studied as well.Our results show that CR induced changes in hepatocyte and mitochondrial size, in the volume fraction occupied by mitochondria, and in the number of mitochondria per hepatocyte. Also, mean number of mitochondrial cristae and lengths were significantly higher in all CR groups compared with controls. Finally, CR had no remarkable effects on the expression levels of fission and fusion protein markers. However, considerable differences in many of these parameters were found when comparing the CR groups, supportingthe idea that dietary fat plays a relevant role in the modulation of CR effects in aged mice.
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