Effect of senescence on Ca2+-ion transport by heart mitochondria.

Both the rate of uptake of Ca2+ into isolated rat heart mitochondria and the rate of release of Ca2+ by a separate, Na+-dependent, pathway were shown to be diminished in senescence (24-month relative to 6-month animal). These processes were studied at lower concentrations of Ca2+ and loads of Ca2+ per mg of mitochondrial protein than those generally employed, and it is argued that these are more appropriate physiologically. In addition, Ca2+ release was characterized in terms of the sum of the added Ca2+ and the endogenous Ca2+ of the mitochondrial preparation; the endogenous Ca2+ content was found to be unchanged with age. The decrements in rates of transport are not caused by altered rates of substrate oxidation and are inferred to reflect decreased carrier-protein content or activity. The buffering of extramitochondrial free Ca2+ concentration by heart mitochondria was studied and found to be less than complete at mitochondrial Ca2+ loads inferred to be physiological. No change was shown in senescence, in keeping with the essentially equal age-linked decrements in the activity of mitochondrial Ca2+ uptake and release.