Quantitative proteomic analysis of changes related to age and calorie restriction in rat liver tissue

Abstract

Calorie restriction (CR) is the most frequently studied mechanism for increasing longevity, protecting against stress, and delaying age-associated diseases. Most studies have initiated CR in young animals to determine the protective effects against aging. Although aging phenomena are well-documented, the molecular mechanisms of aging and CR remain unclear. In this study, we observed changes in hepatic proteins upon age-related and dietrestricted changes in the rat liver using quantitative proteomics. Quantitative proteomes were measured using tandem mass tag (TMT) labeling followed by liquid chromatography-tandem mass spectrometry. We compared protein levels in livers from young (6-months-old) and old (25-months-old) rats with 40% calorie-restricted (YCR and OCR, respectively) or ad libitum diets. In total, 44,279 peptides and 3,134 proteins were identified and 260 differentially expressed proteins were found. Functional enrichment analysis showed that these proteins were mainly involved in glucose and fatty acid metabolism-related processes, consistent with the theory that energy metabolism regulation is dependent on age-related and calorierestricted changes in liver tissue. In addition, proteins mediating inflammation and gluconeogenesis were increased in OCR livers, but not YCR livers. These results showed that CR in old rats might not have anti-aging benefits because liver inflammation was increased. C 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim