EFFECTS OF CALORIC RESTRICTION AND AGING ON ERYTHROCYTE-MEMBRANE CA-2+-ATPASE ACTIVITY IN SPECIFIC PATHOGEN-FREE FISCHER-344 RATS

Dietary caloric restriction extends life span in the Fischer 344 rat. The interaction of aging and caloric restriction was examined at the level of the plasma membrane transport-associated enzymes, Ca2+-adenosine triphosphatase (ATPase) and Na,K-ATPase, in the Fischer rat. Animals were in four age groups, ranging from 6.1 to 25.0 months, and were specific pathogen-free (SPF, barrier-raised). Results from male and female animals raised on an ad libitum diet were compared with those from rats that received 60% of the age-specific caloric intake of their ad lib littermates. The responses of erythrocyte membrane Ca2+-ATPase activity in vitro to thyroid hormone (l-thyroxine [T4]; 3,5,3′-triiodothyronine [T3]) and to purified calmodulin, a Ca2+-binding protein activator of Ca2+-ATPase, were measured. Erythrocyte membrane Na,K-ATPase was also compared in the two diet groups, as was plasma glucose. Plasma membrane Ca2+-ATPase activity in the absence of added thyroid hormone and calmodulin was significantly reduced in calorically restricted rats (-39%, P < .001), compared with ad lib-fed animals, and the response was similar in the four age groups aged 6.1, 12.7, 17.0, and 25.0 months. In contrast, pooled (all ages) Ca2+-ATPase response in vitro to T4 and to T3 in calorically restricted animals was enhanced compared with the ad lib group (+62% and +58%, P < .001, respectively). Calmodulin responsiveness of the enzyme was increased by 45% (P < .001) in calorie-deprived animals, similar to the change in T4 and T3 responsiveness. Analyzed on an age-specific basis, the diet-related difference in calmodulin responsiveness of Ca2+-ATPase activity was found to be greatest in young (6 months) animals; the diet effect was lessened in the 13-, 17- and 25-month-old rats. Diet-conditioned heightening of T4 and T3 stimulation of Ca2+-ATPase activity was similar in all age groups. There were no sex-, age-, or diet-dependent effects on red blood cell (RBC) Na,K-ATPase activity. There was no significant difference in plasma glucose levels between the ad lib and calorie-restricted animals. Thus, chronic caloric restriction in Fischer 344 SPF rats reduces RBC membrane Ca2+-ATPase, but not Na,K-ATPase, activity in animals ranging in age from 6 to 25 months. In contrast, the restricted diet was associated with significantly increased Ca2+-ATPase response in vitro to T4, T3, and calmodulin. The enhanced response to calmodulin was most marked in the 6-month age group. © 1991.