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Caloric restriction counteracts age-related changes in the activities of sorbitol metabolizing enzymes from mouse liver

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Abstract

The influence of caloric restriction (CR) on hepatic sorbitol-metabolizing enzyme activities was investigated in young and old mice. Aldose reductase and sorbitol dehydrogenase activities were significantly lower in old CR mice than in old controls. Young CR mice showed decreased aldose reductase activity and a trend towards decreased sorbitol dehydrogenase when compared to controls. Metabolites of the pathway, namely sorbitol, glucose and fructose were decreased by CR in young and old mice. Pyruvate levels were decreased by CR in both young and old mice, while lactate decreased only in old CR. Malate levels increased in old CR but remained unchanged in young CR, when compared with controls. Accordingly, the lactate/pyruvate and malate/pyruvate ratios in young and old CR mice were increased, indicating increased NADH/NAD and NADPH/NADP redox couples, respectively. The results indicate that decreased glucose levels under CR conditions lead to decreased sorbitol pathway enzyme activities and metabolite levels, and could contribute to the beneficial effects of long-term CR through decreased sorbitol levels and NADPH sparing.

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Abbreviations

CR:

Caloric restriction

SDH:

Sorbitol dehydrogenase

AR:

Aldose reductase

ROS:

Reactive oxygen species

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Acknowledgment

The work was supported by the National Institutes of Health grants PO1 AG11915 and RO1 AG028125.

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Authors and Affiliations

  1. Department of Molecular Biosciences, School of Veterinary Medicine, University of California, One Shields Ave, Davis, CA, 95616, USA

    Kevork Hagopian & Jon J. Ramsey

  2. Department of Medicine, University of Wisconsin Medical School, Madison, WI, 53706, USA

    Richard Weindruch

  3. Geriatric Research, Educational and Clinical Center, William S. Middleton Memorial Veterans Hospital, 2500 Overlook Terrace, Madison, WI, 53705, USA

    Richard Weindruch

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  1. Kevork Hagopian
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  2. Jon J. Ramsey
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Correspondence to Kevork Hagopian.

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Hagopian, K., Ramsey, J.J. & Weindruch, R. Caloric restriction counteracts age-related changes in the activities of sorbitol metabolizing enzymes from mouse liver. Biogerontology 10, 471–479 (2009). https://doi.org/10.1007/s10522-008-9191-1

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