Age-Related Cardiac Muscle Sarcopenia: Combining experimental and mathematical modeling to identify mechanisms
| Autor: | Yufang Jin, Hai Chao Han, Elizabeth F. Lopez, Holly Van Remmen, Merry L. Lindsey, Terry Bauch, Jing Lin |
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| Jazyk: | angličtina |
| Rok vydání: | 2007 |
| Předmět: |
Male
medicine.medical_specialty Aging Diastole Biochemistry Models Biological Article Ventricular Function Left Muscle hypertrophy Electrocardiography Mice Endocrinology Fibrosis Internal medicine Genetics Medicine Myocyte Animals Myocytes Cardiac Molecular Biology business.industry Myocardium Cardiac muscle Skeletal muscle Heart Cell Biology medicine.disease Lipid Metabolism Myocardial Contraction Mice Inbred C57BL Muscular Atrophy medicine.anatomical_structure Sarcopenia Cardiology End-diastolic volume Female Collagen business Glycogen |
| Popis: | Age-related skeletal muscle sarcopenia has been extensively studied and smooth muscle sarcopenia has been recently described, but age-related cardiac sarcopenia has not been previously examined. Therefore, we evaluated adult (7.5 ± 0.5 months; n = 27) and senescent (31.8 ± 0.4 months; n = 26) C57BL/6J mice for cardiac sarcopenia using physiological, histological, and biochemical assessments. Mice do not develop hypertension, even into senescence, which allowed us to decouple vascular effects and monitor cardiac-dependent variables. We then developed a mathematical model to describe the relationship between age-related changes in cardiac muscle structure and function. Our results showed that, compared to adult mice, senescent mice demonstrated increased left ventricular (LV) end diastolic dimension, decreased wall thickness, and decreased ejection fraction, indicating dilation and reduced contractile performance. Myocyte numbers decreased, and interstitial fibrosis was punctated but doubled in the senescent mice, indicating reparative fibrosis. Electrocardiogram analysis showed that PR interval and QRS interval increased and R amplitude decreased in the senescent mice, indicating prolonged conduction times consistent with increased fibrosis. Intracellular lipid accumulation was accompanied by a decrease in glycogen stores in the senescent mice. Mathematical simulation indicated that changes in LV dimension, collagen deposition, wall stress, and wall stiffness precede LV dysfunction. We conclude that age-related cardiac sarcopenia occurs in mice and that LV remodeling due to increased end diastolic pressure could be an underlying mechanism for age-related LV dysfunction. |
| Databáze: | OpenAIRE |
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