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This Article Full Text Full Text (PDF) All Versions of this Article: 292/6/F1751    most recent 00307.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Web of Science (3) Citing Articles via Google Scholar Google Scholar Articles by McKiernan, S. H. Articles by Aiken, J. M. Search for Related Content PubMed PubMed Citation Articles by McKiernan, S. H. Articles by Aiken, J. M.

Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells

¹Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison; ²Department of Medicine, University of Wisconsin, Madison, Wisconsin; and ³Division of Gerontology and Geriatric Medicine, University of Washington, Seattle, Washington

Submitted 4 August 2006 ; accepted in final form 28 February 2007

Adult-onset calorie restriction (A-CR) is an experimental model of life extension and healthy aging less explored, compared with calorie restriction begun at early ages, but one more realistic for human application. We examined the effect of A-CR on the aging rat kidney with respect to common structural age-dependent changes and the accumulation of mitochondrial enzyme abnormalities in tubular epithelial cells. A 40% calorie restriction was initiated in middle-aged rats, before the onset of significant age-related changes in the Fischer x Brown Norway rat kidney. This dietary intervention effectively reduced glomerulosclerosis and tubular atrophy within 6 mo and changed the rate of interstitial fibrosis formation within 1 yr and vascular wall thickening and the expression cytochrome c oxidase (COX)-deficient tubular epithelial cells in 18 mo compared with age-matched ad libitum-fed rats. Our histological approach (histochemical staining for mitochondrial enzyme activity and laser capture microdissection) coupled with mitochondrial DNA (mtDNA) PCR analyses demonstrated that COX-deficient renal tubular epithelial cells accumulated mtDNA deletion mutations and that these cells contained unique, clonally expanded mtDNA deletion mutations. Renal tubular epithelial cells with mitochondrial abnormalities presented cellular characteristics indicative of physiological dysfunction.

dietary restriction; cytochrome c oxidase; mtDNA deletion mutations