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OR, Fig. These numbers suggest that a considerable part of the CR effects is independent of age. Consistently, Venn diagram representation of the data Fig. OR were also present in O vs. OR comparison. O, B old calorically restricted OR vs. Spots that pass the criteria are shown in white.

Venn diagram illustrating the overlap of Y vs. O, O vs. OR comparisons. To improve the visualization of difference distribution between these groups, a principal component analysis PCA was used to cluster the individual animals based on expression patterns. The first two principal components of the variance are plotted in Fig. Samples with similar protein expression profiles will cluster together in such a graph.

Altogether, these analyses suggest that CR exerts a greater number of changes on WAT proteome than age does, and therefore CR cannot be considered simply as a manipulation preventing or delaying the effects of age on protein expression. Principal component analysis PCA of significantly changed spots. Principal component analysis allows visualization of the protein expression pattern of individual rats. This led to the identification of 57 differentially expressed proteins corresponding to 47 different gene products.

Does eating less make you live longer and better? An update on calorie restriction

Furthermore, several proteins were identified at multiple spot positions [e. In these cases, however, the variation of the spots, on average, was similar. Differentially expressed spots in white adipose tissue of Y, O and old calorically restricted rats. On the basis of the identities of these proteins, we grouped them into several functional categories: i metabolism, ii oxidative stress iii stress response, iv iron homeostasis v cellular structure, vi energy transduction and vii others.

The main group of proteins regulated by aging and CR were metabolic enzymes. These include enzymes involved in glucose, intermediate and lipid metabolism. Caloric restriction proteome showed a higher expression of several proteins associated with lipid metabolism. As shown in Fig.

Example of differential expression of white adipose tissue proteins involved in lipid metabolism. Example of differential expression of white adipose tissue WAT proteins related to antioxidant system. Left, representative blot images. Our data reveal that several enzymes involved in cell protection against oxidative stress are increased by CR, whereas these protein levels decrease or do not change with age Fig. In contrast to antioxidant enzymes, other stress response proteins were regulated by aging and CR in a different manner. Spots corresponding to ferritin heavy spots , and light chains spot were increased by CR, whereas serotransferrin spot was decreased.

Aging and CR were found to modify several spots related to cell structure and cytoskeleton rearrangement. A major group of proteins identified herein are proteins whose function is not well understood yet, but with an accumulating body of evidence suggesting a role in adipocyte physiology. Because of the high vascularization of WAT with an extensive capillary network surrounding each adipocyte, several blood proteins were also detected in our study such as hemoglobin spot , , hemopexin spots , and albumin spot To gain a broader understanding of the molecular events underlying CR benefits and to overcome the limits of transcriptomics with respect to cellular behavior, we examined the changes in the proteome of WAT from young, old and old CR rats.

Comparison across all three animal groups allows us to identify three different protein expression patterns of interest: i proteins that change with age regardless of diet; ii proteins with an ad libitum aging change that is counteracted by CR and iii proteins with CR effects but little or no aging effect.

Original Research ARTICLE

The largest group of proteins identified in our study was metabolic enzymes involved in carbohydrate, lipid and intermediate metabolism. These enzymes catalyze, respectively, the two last steps of glycolysis, with KPYM catalyzing one of the highly regulated reactions of the pathway. Caloric restriction was found to increase the expression of the enzymes involved in oxalacetate synthesis, i.

The expression of these anaplerotic enzymes, together with the decrease in PDC and KPYM, suggests a mitochondrial metabolic shift toward lipogenesis.

Benefits of caloric restriction in the myenteric neuronal plasticity in aging rats

Furthermore, CR also increased the levels of transketolase TKT , an enzyme directly involved in the branch of the pentose phosphate pathway that channels excess sugar phosphates to glycolysis, and which enables the production of more NADPH. These metabolic features, i. In support, we found that adipose tissue from OR rats expresses higher levels of several proteins closely related to lipogenesis.

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Caloric Restriction Mimetics in Aging, Improved Cancer Chemotherapy, Autophagy Anti-Obesity Effect

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