Age-induced decreases in the messenger RNA coding for the sarcoplasmic reticulum Ca2(+)-ATPase of the rat heart.

Abstract

Age-associated slowing of cardiac relaxation related to the decline in the Ca2+ pump function of cardiac sarcoplasmic reticulum (SR) has been previously described. It is unclear if the decreased Ca2+ pump function results from a lower amount of Ca2(+)-ATPase protein or a decreased pumping activity of the enzyme. To determine if these alterations could be mediated by changes in the amount of the protein itself, the level of the messenger RNA (mRNA) coding for the Ca2(+)-ATPase of the SR of Fischer rat hearts (4- and 30-month-old rats) were quantitated with a Northern blotting technique. We observed that the levels of SR Ca2(+)-ATPase mRNA were 60% lower in old rats as compared with young rats, suggesting that a quantitative reduction in the levels of the corresponding protein could occur during aging to explain the delayed diastolic relaxation documented in old animals as opposed to a change in the specific activity of this enzyme. The thyroid hormone responsiveness of SR Ca2(+)-ATPase mRNA has been previously established. We have found in this study that the thyroxine levels were consistently lower in old rats; however, this difference was relatively small (4.3 +/- 0.7 and 3.1 +/- 0.8 micrograms/dl [mean +/- SD), respectively, in young and old rats). In addition, no age-induced decrease in 3,5,3'-triiodothyronine levels was observed, suggesting that the aging process itself may be responsible for the changes in SR Ca2(+)-ATPase mRNA levels.