Impairment of hepatic cholesterol synthesis from squalene and the function of hepatic sterol carrier protein system by ageing

Incorporations of squalene and mevalonate into cholesterol in hepatic microsomes and cytosol from growing or young rats were higher than those from adult rats. When the microsomes from growing or young rats were combined with the cytosol from adult rats instead of young cytosol, the incorporation rates of squalene and mevalonate into cholesterol were decreased. When adult microsomes were combined with young cytosol, cholesterol synthesis from mevalonate was increased but that from squalene was not. Cytosol fractions from cholesterol fed rats did not inhibit the cholesterol synthesis from squalene in the microsomes from non-treated rats, and the normal cytosol did not influence the cholesterol synthesis in the microsomes from cholesterol fed rats, suggesting the elevation of serum cholesterol in aged animals did not affect the activity of cytosol fraction. It is concluded that the function of hepatic sterol carrier protein is probably impaired by ageing process. The decrease of hepatic cholesterol synthesis in old microsomes in vitro is difficult to be recovered by the substitution of young sterol carrier protein for adult one. The decreased function of sterol carrier protein is not derived from hypercholesterolemia which is often observed in the aged.