Age-related down regulation of hepatic cytochrome P1-450, P3-450, catalase and CuZn-superoxide dismutase RNA.
The influence of age on liver gene expression was investigated in two strains of H-2 congenic mice. In B10.RIII mice (H-2r), basal P1- and P3-450 RNA levels progressively decreased 65 and 95%, respectively, between 4 and 28 months of age (P less than or equal to 0.05). Polyaromatic hydrocarbon (PAH) induced P1- and P3-450 RNA levels decreased about 50% during this time (P less than or equal to 0.05). In contrast, in C57BL/10 mice (H-2b) little or no change was detected in basal or induced P1- or P3-450 RNA levels. CuZn-superoxide dismutase RNA decreased 80 to 90% between 4 and 9 months of age in B10.RIII mice, while a quantitatively smaller decrease of 50 to 65% was found in C57BL/10 mice (P less than or equal to 0.05). Catalase RNA decreased approximately 80% between 4 and 9 months of age in B10.RIII mice, and a similar decrease was found in C57BL/10 mice. Down regulation of these genes may explain the reduced activities of the cognate hepatic enzymes, and reduced xenobiotic metabolism found in older animals.
Department of Biochemistry, University of California, Riverside 92521.
P L
PL
Mote
J M
JM
Grizzle
R L
RL
Walford
S R
SR
Spindler
D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002374:Catalase / Q000235:genetics / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D015536:Down-Regulation / Q000235:genetics; D015870:Gene Expression; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012313:RNA / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*
D012313:RNA; D003577:Cytochrome P-450 Enzyme System; D002374:Catalase; D013482:Superoxide Dismutase