EFFECT OF LONG-TERM FOOD RESTRICTION ON CARDIAC MECHANICS

Food restriction (FR) is the only known intervention capable of increa sing mammalian life span. It not only increases longevity, but reduces the incidence of a broad spectrum of age-related pathologies, includi ng cardiomyopathy, and retards the physiological decline associated wi th aging. Previous work from this laboratory has shown that long-term FR affects the contractile machinery of the heart, shifting the cardia c myosin profile from the fast, V-1 isoform to the slow, V-3 isoform. The aim of the present study was to determine whether FR also induces changes in cardiac mechanics. Isolated, isovolumically beating hearts were examined from four groups of rats: 1) ad Libitum-fed rats killed at 10-13 mo of age, 2) FR rats offered only 60% of the calories consum ed by ad libitum-fed rats and killed at the same age, 3) young ad Libi tum-fed rats having the same heart weights as the FR rats, and 4) ad L ibitum-fed rats subjected to short-term FR, i.e., for the last 3 wk of life, and also killed at 10-13 mo of age. Both short-and long-term FR profoundly and to approximately the same extent affected cardiac mech anics. Hearts from FR rats developed much higher pressures than hearts from the ad Libitum-fed rats under conditions of low-calcium perfusat e. This difference disappeared, however, when contractility was enhanc ed by either calcium or isoproterenol. FR prolonged both contraction a nd relaxation times. Long-term ad libitum-fed rats (adult, 10-13 mo of age) had a lower isoproterenol sensitivity than the young ad Libitum- fed rats (10 wk of age). Both short-and long-term FR restored the sens itivity to isoproterenol. In summary, FR profoundly affects many aspec ts of cardiac mechanics, enhancing some age-related changes (prolongat ion of the contraction and relaxation times), attenuating another (inc reasing the isoproterenol sensitivity), and, finally, inducing some un ique changes unrelated to age (increased pressure development under lo w-calcium perfusate).