TY - JOUR
T1 - Age-related cardiac muscle sarcopenia
T2 - Combining experimental and mathematical modeling to identify mechanisms
AU - Lin, Jing
AU - Lopez, Elizabeth F.
AU - Jin, Yufang
AU - Van Remmen, Holly
AU - Bauch, Terry
AU - Han, Hai Chao
AU - Lindsey, Merry L.
N1 - Funding Information:
The authors acknowledge support from the NIH (R01 HL-75360- MLL and P01 AG-20591-HVR) and the NSF (0602834-HCH, CAREER award 0644646-HCH and 0649172-YJ).
PY - 2008/4
Y1 - 2008/4
N2 - 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.
AB - 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.
KW - Aging
KW - Cardiac
KW - Fibrosis
KW - Hypertrophy
KW - Sarcopenia
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U2 - 10.1016/j.exger.2007.12.005
DO - 10.1016/j.exger.2007.12.005
M3 - Article
C2 - 18221848
AN - SCOPUS:40649109044
VL - 43
SP - 296
EP - 306
JO - Experimental Gerontology
JF - Experimental Gerontology
SN - 0531-5565
IS - 4
ER -