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Aging might increase myocardial ischemia / reperfusion-induced apoptosis in humans and rats

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Abstract

Previous studies indicated aging results in the significant cardiac function decreasing and myocardial apoptosis increasing in normal humans or rats. Additionally, animal experiments demonstrated aging increased myocardial ischemia / reperfusion (MI/R)-induced apoptosis. However, whether more myocardial apoptosis happen in the old acute myocardial infarction (AMI) patients is unclear. Reperfusion injury-induced apoptosis is an important cause of heart failure. This study determined the effect of aging upon myocardial apoptosis and cardiac function in patients suffering AMI. All enrolled AMI patients received percutaneous coronary intervention therapy. Volunteers and AMI patients were assigned to four groups: adult (age <65, n = 24) volunteers, elderly (age ≥65, n = 21) volunteers, adult (age <65, n = 29) AMI patients, and elderly (age ≥65, n = 36) AMI patients. Blood samples were obtained from all study participants. Plasma apoptotic markers (soluble form of Fas, tumor necrosis factor alpha, and interleukin 6) levels were determined. Cardiac function was evaluated with echocardiogram and Killip class. Due to lack of a direct apoptotic assay method in live human subjects, an additional animal experiment was performed. Both young (2 months) and old (24 months) rats were subjected to 30-min myocardial ischemia and 3 (for TUNEL/caspase activity apoptotic assay) or 24-h (for cardiac function determination) reperfusion. Compared to adult patients, the elderly patients manifested decreased cardiac function and increased plasma apoptotic marker levels significantly. The animal experiment results (cardiac function and plasma apoptotic markers assays) were consistent with the human result data. Animal TUNEL staining and caspase activity measurement revealed a higher myocardial apoptotic ratio in the older rat group. Aging exacerbated MI/R injury in humans and rats. Differential myocardial apoptosis may play a vital role in mediating the observed effects.

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Acknowledgments

This study was supported by National Natural Sciences Foundation of China (NSFC) grants (30800448, to Qian Fan). We thank Prof. Xin Liang Ma for his excellent work in the manuscript revision.

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Authors and Affiliations

  1. Department of Gerontology, Beijing Chaoyang Hospital—Affiliate of Capital Medical University, 8 Gongtinan Road, Beijing, 100020, China

    Miaobing Liu

  2. Department of Gerontology, Beijing Jishuitan Hospital, 31 Xinjiekoudong Road, Beijing, 100035, China

    Ping Zhang

  3. Heart Center, Beijing Chaoyang Hospital—Affiliate of Capital Medical University, 8 Gongtinan Road, Beijing, 100020, China

    Mulei Chen, Wuning Zhang, Liping Yu, Xin-Chun Yang & Qian Fan

Authors
  1. Miaobing Liu
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  2. Ping Zhang
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  3. Mulei Chen
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  4. Wuning Zhang
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  5. Liping Yu
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  6. Xin-Chun Yang
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  7. Qian Fan
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Corresponding authors

Correspondence to Xin-Chun Yang or Qian Fan.

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Miaobing Liu and Ping Zhang contributed equally to this study.

Xin Chun Yang is the second corresponding author.

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Liu, M., Zhang, P., Chen, M. et al. Aging might increase myocardial ischemia / reperfusion-induced apoptosis in humans and rats. AGE 34, 621–632 (2012). https://doi.org/10.1007/s11357-011-9259-8

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  • DOI: https://doi.org/10.1007/s11357-011-9259-8

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