Calorie restriction can reverse, as well as prevent, aging cardiomyopathy
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Calorie restriction (CR) is the most widely studied intervention protecting from the adverse effects of aging. Almost all prior studies have examined the effects of CR initiated in young animals. Studies examining the effects of CR on development of aging cardiomyopathy found only partial prevention. The major goal of this study was to determine whether CR initiated after aging cardiomyopathy developed could reverse the cardiomyopathy. Aging cardiomyopathy in 2-year-old mice was characterized by reduced left ventricular (LV) function, cardiac hypertrophy, and increased cardiac apoptosis and fibrosis. When short-term (2 months) CR was initiated after aging cardiomyopathy developed in 20-month-old mice, the decrease in cardiac function, and increases in LV weight, myocardial fibrosis and apoptosis were reversed, such that the aging hearts in these mice were indistinguishable from those of young mice or mice where CR was initiated in young mice. If apoptosis was the mechanism for protecting against aging cardiomyopathy, then total myocyte numbers should have reverted to normal with CR, but did not. However, the alterations in cytoskeletal proteins, which contribute to aging cardiomyopathy, were no longer observed with CR. This is the first study to demonstrate complete prevention of aging cardiomyopathy by CR and, more importantly, that instituting this intervention even later in life can rapidly correct aging cardiomyopathy, which could have important therapeutic implications.
KeywordsCalorie restriction Aging Cardiomyopathy Apoptosis Myocyte loss
We thank Serge Salganik for statistical analysis and Dr. Doru Chirieac for technical help. This work was supported by the National Institute of Health grants 5P01AG027211, 5R21HL097264, 1R01HL102472, 5R01HL033107, 5T32HL069752, 5R01HL095888, 5P01HL069020, and 5R01HL091781.
- Afilalo J, Sebag IA, Chalifour LE, Rivas D, Akter R, Sharma K , Duque G (2007). Age-related changes in lamin A/C expression in cardiomyocytes. Am J Physiol Heart Circ Physiol 293:H1451–1456Google Scholar
- Boyle AJ, Shih H, Hwang J, Ye J, Lee B, Zhang Y, Kwon D, Jun K, Zheng D, Sievers R et al (2011) Cardiomyopathy of aging in the mammalian heart is characterized by myocardial hypertrophy, fibrosis and a predisposition towards cardiomyocyte apoptosis and autophagy. Exp Gerontol 46:549–559PubMedCrossRefGoogle Scholar
- Gardin JM, Henry WL, Savage DD, Ware JH, Burn C, Borer JS (1979). Echocardiographic measurements in normal subjects: evaluation of an adult population without clinically apparent heart disease. J Clin Ultrasound. 7: 439–447Google Scholar
- Iemitsu M, Miyauchi T, Maeda S, Tanabe T, Takanashi M, Irukayama-Tomobe Y, Sakai S, Ohmori H, Matsuda M , Yamaguchi I (2002). Aging-induced decrease in the PPAR-alpha level in hearts is improved by exercise training. Am J Physiol Heart Circ Physiol 283:H1750–1760Google Scholar
- Luptak I, Yan J, Cui L, Jain M, Liao R , Tian R (2007). Long-term effects of increased glucose entry on mouse hearts during normal aging and ischemic stress. Circulation 116:901–909Google Scholar
- Pavlik G, Olexo Z, Osvath P, Sido Z , Frenkl R (2001). Echocardiographic characteristics of male athletes of different age. Br J Sports Med 35:95–99Google Scholar
- Rodeheffer RJ, Gerstenblith G, Becker LC, Fleg JL, Weisfeldt ML , Lakatta EG (1984). Exercise cardiac output is maintained with advancing age in healthy human subjects: cardiac dilatation and increased stroke volume compensate for a diminished heart rate. Circulation 69:203–213Google Scholar