Adult-onset calorie restriction delays the accumulation of mitochondrial enzyme abnormalities in aging rat kidney tubular epithelial cells.
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.
McKiernan
Susan H
SH
Department of Animal Health and Biomedical Sciences, University of Wisconsin, Madison, WI 53706, USA. mckiernan@svm.vetmed.wisc.edu
Tuen
Victoria C
VC
Baldwin
Katherine
K
Wanagat
Jonathan
J
Djamali
Arjang
A
Aiken
Judd M
JM
D000375:Aging / Q000502:physiology*; D000818:Animals; D001835:Body Weight / Q000502:physiology; D031204:Caloric Restriction; D004272:DNA, Mitochondrial / Q000235:genetics; D004032:Diet; D003576:Electron Transport Complex IV / Q000378:metabolism; D004847:Epithelial Cells / Q000201:enzymology; D017353:Gene Deletion; D007684:Kidney Tubules / Q000166:cytology / Q000201:enzymology*; D007834:Lasers; D008297:Male; D008928:Mitochondria / Q000201:enzymology*; D009929:Organ Size / Q000502:physiology; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013385:Succinate Dehydrogenase / Q000378:metabolism
D004272:DNA, Mitochondrial; D013385:Succinate Dehydrogenase; D003576:Electron Transport Complex IV