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.

Changes in Mitochondrial Status Associated with Altered Ca2+Homeostasis in Aged Cerebellar Granule Neurons in Brain Slices

“…A delay in the recovery of resting [Ca 2ϩ ] i after stimulation could be attributable to an alteration of one of the Ca 2ϩ extrusion systems. In non-neuronal tissues, an agedependent decrease in the expression of the gene coding for one sarco/endoplasmic reticulum (ER) Ca 2ϩ -ATPase (SERCA) subtype has been reported previously (Maciel et al, 1990); in peripheral neurons, a decrease in the activity of either SERCA (Pottorf et al, 2000) or plasma membrane Ca 2ϩ -ATPase (PMCA) (Michaelis et al, 1996) was demonstrated that was linked, directly or indirectly, with alterations in the calmodulindependent activation step. In central neurons, direct measurements of the caffeine-sensitive Ca 2ϩ pools showed that aging results in a decrease in the ER Ca 2ϩ pools (Verkhratsky et al, 1994).…”

Ageing-dependent remodelling of ion channel and Ca2+clock genes underlying sino-atrial node pacemaking

“…6D). In contrast, there was a small age-dependent increase in SERCA2a in the SAN (although an agedependent decline has been reported in rat ventricle; Maciel et al 1990). However, like the decrease in RYR2, the increase in SERCA2a could decrease the intracellular Ca 2+ transient and, therefore, pacemaking.…”

Overexpression of the Sarcoplasmic Reticulum Ca2+-ATPase Improves Myocardial Contractility in Diabetic Cardiomyopathy

“…Impaired SR function and decreased SERCA2a levels are not unique to diabetic cardiomyopathy and play a role in end-stage heart failure due to ischemic and dilated cardiomyopathy (32)(33)(34), hypertrophic cardiomyopathy (35), and aging hearts (36). In fact, a recent study on heart failure in rats demonstrated an improvement in contractile function after gene transfer of SERCA2a using adenoviral vectors (37).…”