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

Kevork Hagopian, Jon J Ramsey, Richard Weindruch

Research output: Contribution to journalArticle

8 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)471-479
Number of pages9
JournalBiogerontology
Volume10
Issue number4
DOIs
StatePublished - 2009

Keywords

  • Aldose reductase
  • Fructose
  • Glucose
  • Polyol
  • Redox state
  • Sorbitol dehydrogenase

ASJC Scopus subject areas

  • Geriatrics and Gerontology
  • Gerontology
  • Aging

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