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.
Mote
P L
PL
Department of Biochemistry, University of California, Riverside 92521.
Grizzle
J M
JM
Walford
R L
RL
Spindler
S R
SR
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