OBJECTIVES: We determined whether caloric restriction (CR) has cardiac-specific effects that attenuate the established aging-associated impairments in diastolic function (DF). BACKGROUND: Caloric restriction retards the aging process in small mammals; however, no information is available on the effects of long-term CR on human aging. In healthy individuals, Doppler echocardiography has established the pattern of aging-associated DF impairment, whereas little change is observed in systolic function (SF). METHODS: Diastolic function was assessed in 25 subjects (age 53 ± 12 years) practicing CR for 6.5 ± 4.6 years and 25 age- and gender-matched control subjects consuming Western diets. Diastolic function was quantified by transmitral flow, Doppler tissue imaging, and model-based image processing (MBIP) of E waves. C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-beta1 (TGF-β1) were also measured. RESULTS: No difference in SF was observed between groups; however, standard transmitral Doppler flow DF indexes of the CR group were similar to those of younger individuals, and MBIP-based, flow-derived DF indexes, reflecting chamber viscoelasticity and stiffness, were significantly lower than in control subjects. Blood pressure, serum CRP, TNF-α, and TGF-β1 levels were significantly lower in the CR group (102 ± 10/61 ± 7 mm Hg, 0.3 ± 0.3 mg/l, 0.8 ± 0.5 pg/ml, 29.4 ± 6.9 ng/ml, respectively) compared with the Western diet group (131 ± 11/83 ± 6 mm Hg, 1.9 ± 2.8 mg/l, 1.5 ± 1.0 pg/ml, 35.4 ± 7.1 ng/ml, respectively). CONCLUSIONS: Caloric restriction has cardiac-specific effects that ameliorate aging-associated changes in DF. These beneficial effects on cardiac function might be mediated by the effect of CR on blood pressure, systemic inflammation, and myocardial fibrosis.