Journal
EXPERIMENTAL CELL RESEARCH
Volume 403, Issue 1, Pages -Publisher
ELSEVIER INC
DOI: 10.1016/j.yexcr.2021.112585
Keywords
Lipofuscin; Senescence; Myocardium; Conducting tissue; Autophagy; Rapamycin
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Funding
- National Natural Science Foundation of China [81470385, 81770288, 81870215]
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The study found that in aging hearts, there is an increase in lipofuscin accumulation and senescent cardiomyocytes, along with a decrease in autophagy levels. Enhancing autophagy with rapamycin was effective in reducing lipofuscinogenesis and promoting degradation of lipofuscin, offering a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.
Cardiomyocytes are particularly prone to lipofuscin accumulation. In the aging heart, lipofuscin accumulation is augmented. This study examined distribution of lipofuscin and senescent cardiomyocytes and evaluated improvement of lipofuscin accumulation and cardiomyocytic senescence of the aging heart after treatment with rapamycin. The results of Schmorl staining, Sudan black staining and autofluorescence detection showed that there was more lipofuscin in the myocardium of the ventricles especially in the left ventricle. The conductive tissue contained less lipofuscin than the myocardium. In the aged hearts, lipofuscin accumulation and senescent cardiomyocytes were increased, and the level of autophagy was reduced. In double staining of Sudan black B and senescence-associated beta-galactosidase, 10%-20% lipofuscin-loaded cardiomyocytes became senescent. All senescent cardiomyocytes contained lipofuscin deposits. After enhancing autophagy with feed of rapamycin for six months, lipofuscin accumulation and senescence of cardiomyocytes were improved in old rats. Colocalization of autophagic structure and lipofuscin as well as electron micrographs showed that some lipofuscin-loaded lysosomes were sequestrated by autophagic structures. This study suggests that rapamycin-enhanced autopahgy is effective for reducing lipofuscinogenesis and promoting degradation of lipofuscin. Therefore, enhancing autophagy is a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.
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