THE AGE-ASSOCIATED ALTERATIONS IN LATE DIASTOLIC FUNCTION IN MICE AREIMPROVED BY CALORIC RESTRICTION

Caloric restriction reduces the magnitude of many age-related changes tt rodents. Cardiac function is altered with senescence in mice, rats, and healthy humans. We examined the effects of life-long caloric rest riction on diastolic and systolic cardiac function in situ using Doppl er techniques irt ad libitum-fed 30- to 32-month-old (AL) and calorica lly restricted (CR) 32- to 35-month-old female B6D2-F-1 hybrid mice. T he heart weight to body weight ratio was similar in AL (5.74 +/- .24 m g/g) and CR (5.68 +/- .20 mg/g) mice. Two systolic functional paramete rs known to decrease with age ill both humans and mice, peak aortic ve locity and aortic acceleration, were unchanged by CR compared to AL. I n contrast, diastolic function was altered by caloric restriction. Alt hough left ventricular peak early piling velocity (E) was not differen t between CR and AL, peak atrial filling velocity (A) was 50% lower il l CR compared to AL (p <.001). The ratio of early diastolic filling to atrial filling (E/A ratio) was 64% higher in the CR (2.74 +/- .31) th an the AL (1.55 +/- .07; p =.004). The fraction of ventricular filling due to atrial systole, the atrial filling fraction, was also reduced in CR (.21 +/- .04) compared to AL (.36 +/- .02; p =.007). These chang es occurred irt CR without alteration in E deceleration time, which is consistent with improved diastolic function in CR. Through mechanisms that remain unknown, lifelong caloric restriction may prevent the age -related impairments in late diastolic function but does not alter the impairments in systolic or early diastolic cardiac function.