Effect of aging on oxidative metabolism and conjugation in perfused livers of an inbred strain of mice: A pilot study

Abstract

A study was carried out to examine the possibility that altered mitochondrial function with aging might cause changes in hepatic rates of oxygen uptake and β-oxidation of fatty acids. Livers of 2–4 month and 20–25 month old CBA mice were perfused, and rates of respiration and ketogenesis were measured. Livers of old mice had significantly decreased rates of oxygen utilization (190 ± 16 vs 151 ± 9 μmol/gm/hr, p.05) and significantly lower rates of ketogenesis as indicated by rates of acetoacetate and β-hydroxybutyrate production (84 ± 8 vs 63 ± 7, p <.05). To determine whether NADPH supply, which is largely derived from β-oxidation of fatty acids in the fasted state, might be rate limiting for mixed-function oxidation in aged mice, rates of p-nitroanisole O-demethylation were measured in livers of young and old mice. Age had no effect on mixed-function oxidation of p-nitroanisole. Rates of glucuronidation of p-nitrophenol were also not affected by age; however, rates of sulfation of p-nitrophenol were significantly higher in livers of old (7.2 ±.6) than in young (3.5 ± 0.8) mice. This pilot study raises the possibility that the disposition of ingested fatty acids and xenobiotic compounds requiring sulfation may be significantly altered with aging. Moreover, it demonstrates that the perfused mouse livers can be used as a model in aging studies.