Aging affects the drug metabolism systems of rat liver, kidney, colon and lung in a differential fashion.

Microsomes prepared from the liver, lungs, colon and kidney cortex of Sprague Dawley rats of ages 2, 4, 10, 24 and 78 weeks were assessed for hydroxylation activity with the substrate benzo[alpha]pyrene. Liver microsomal activity declined after reaching a peak of activity at 10 weeks. The hydroxylation of benzo[alpha]pyrene by colon, kidney and lung microsomes, however, either remained the same or decreased only slightly. During the age range examined inducibility of hydroxylation activity by beta-naphthoflavone decreased with age in liver but actually increased with age in the extrahepatic tissues. Although phenobarbital did not elicit any increases in liver, kidney or lung, it increased substantially benzo[alpha]pyrene hydroxylation activity in colon microsomes of 78 week old rats. Total cytochrome P-450 content was induced at all age groups in all tissues by beta-naphthoflavone and in all tissues except lung by phenobarbital. Induction of cytochrome P-450 in kidney by phenobarbital was only observed in 24 and 78 week old rats. These data suggest an increased role for extrahepatic activation of benzo[alpha]pyrene with aging. In contrast to total content of cytochrome P-450, the beta-naphthoflavone inducible amount of Form 5 which has a high turnover number for benzo[alpha]pyrene, declined by 55% in liver between 2 weeks and 78 weeks while it increases dramatically in all extrahepatic tissues (from 80 to 138%).