Myocardial lipofuscin accumulation in ageing and sudden cardiac death
Myocardial lipofuscin accumulation in ageing and sudden cardiac death
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DOI：
10.1038/s41598-019-40250-0
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发表时间：
2019-03-01
影响因子：
4.6
通讯作者：
Osawa, Motoki
中科院分区：
文献类型：
--
作者：
Kakimoto, Yu;Okada, Chisa;Osawa, Motoki
脂褐素是高度氧化的蛋白质的细胞内聚集体，其不能在泛素-蛋白酶体系统中被消化，并且主要积聚在溶酶体中，特别是在老化细胞和病理条件下。然而，没有系统的研究已经评估了在人类衰老和心脏性猝死（SCD）的心脏积累的脂褐素。身份不明尸体的年龄估计和死后SCD诊断是法医学中的重要课题。因此，我们的目的是阐明它们与心肌脂褐素积累的相关性。我们收集了76例年龄在20-97岁的尸检患者的心脏样本。组织病理学检查后，心肌脂褐素测定其自身荧光。脂褐素主要积累在核周区，其积累率与年龄呈正相关（r = 0.82）。同时，脂褐素水平在不同死因（包括SCD）中无显著变化。与体重指数、血清脑钠肽水平或心脏重量相关的脂褐素水平也没有显著变化。此外，我们进行了LC 3和p62免疫印迹来评估自噬活性，并且在衰老过程中没有观察到任何变化。因此，脂褐素积累更直接地反映了时间老化，而不是人类心脏病理学。我们的研究揭示了稳定性和实用性的心脏脂褐素测量年龄估计在尸检。
Lipofuscin is an intracellular aggregate of highly oxidized proteins that cannot be digested in the ubiquitin-proteasome system and accumulate mainly in lysosomes, especially in aged cells and pathological conditions. However, no systematic study has evaluated the cardiac accumulation of lipofuscin during human ageing and sudden cardiac death (SCD). Age estimation in unidentified bodies and postmortem SCD diagnosis are important themes in forensics. Thus, we aimed to elucidate their correlations with myocardial lipofuscin accumulation. We collected 76 cardiac samples from autopsy patients aged 20-97 years. After histopathological examination, myocardial lipofuscin was measured using its autofluorescence. Lipofuscin accumulated mainly in the perinuclear zone, and its accumulation rate positively correlated with chronological ageing (r = 0.82). Meanwhile, no significant change in lipofuscin level was observed with different causes of death, including SCD. There was also no significant change in lipofuscin level in relation to body mass index, serum brain natriuretic peptide level, or heart weight. Moreover, we performed LC3 and p62 immunoblotting to evaluate autophagic activity, and no change was observed in ageing. Therefore, lipofuscin accumulation more directly reflects chronological ageing rather than human cardiac pathology. Our study reveals the stability and utility of cardiac lipofuscin measurement for age estimation during autopsy.