(06-02-06) Long-Term Caloric Restriction Ameliorates the Decline in Diastolic Function in Humans

Timothy E. Meyer, PhD*, , S?ndor J. Kov?cs, PhD, MD , Ali A. Ehsani, MD*, , Samuel Klein, MD*, John O. Holloszy, MD* and Luigi Fontana, MD, PhD*, ,*
* Division of Geriatrics and Nutritional Science, Washington University School of Medicine, St. Louis, Missouri
Cardiovascular Biophysics Laboratory, Washington University School of Medicine, St. Louis, Missouri
Division of Human Nutrition, Istituto Superiore di Sanit?, Rome, Italy
Manuscript received April 7, 2005; revised manuscript received July 26, 2005, accepted August 25, 2005.
* Reprint requests and correspondence: Dr. Luigi Fontana, Division of Geriatrics, Washington University School of Medicine, 4566 Scott Avenue, Box 8113, St. Louis, Missouri 63110 (Email: [email protected] ).
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- ), and transforming growth factor-beta1 (TGF-?1) 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- , and TGF-?1 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.

Am Coll Cardiol, 2006; 47:398-402, doi:10.1016/j.jacc.2005.08.069 (Published online 22 December 2005).

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