Reducing lipofuscin accumulation and cardiomyocytic senescence of aging heart by enhancing autophagy
Cardiomyocytes are particularly prone to lipofuscin accumulation. In the aging heart, lipofuscin accumulation is augmented. This study examined distri…
“This study suggests that rapamycin-enhanced autopahgy is effective for reducing lipofuscinogenesis and promoting degradation of lipofuscin. Therefore, enhancing auto- phagy is a novel therapy for alleviating lipofuscin accumulation and myocardial senescence.”
“After treatment with rapamycin, the autophagic structures and lysosomes were increased, and the degenerative mitochondria and residual bodies were decreased. Some residual bodies were enwrapped by multiple membranes. In comparison with the control group (2.42 ± 0.32), the ratios of the cross-section areas of the autophagic structures to that of the cytoplasm in rapamycin group were greater (15.62 ± 4.38, p < 0.01)”
“In Schmorl staining, relative content of lipofuscin in the myocardium was decreased significantly after treatment with rapamycin (Fig. 8A,C). Moreover, SA-β-Gal+ cardiomyocytes in Sudan black staining was decreased (Fig. 8B,D). The ratios of SA-β-Gal+ cardiomyocytes to lip- ofuscin+ cardiomyocytes in the myocardium of the left ventricle was reduced significantly (Fig. 8E).”
“This study reveals that the activated autophagy displays eliminating lipofuscin-loaded lyso- somes. Some LC3-positive structures are colocated with lipofuscin granules. In electron micrographs, some residual bodies were enwrap- ped by multiple membranes. Lipofuscin deposition may disturb integrity and function of lysosomes. Autophagy is essential for turnover of lyso- somes. Rapamycin coordinates activation of autophagic flux and lyso- somal biogenesis [40]. Effective biogenesis of lysosomes is implicated in meeting the demand of rapamycin-activated autophagy [41]. Therefore, we suggest that rapamycin-enhanced autophagy may improve lipofuscin accumulation by reducing lipofuscinogenesis and enhancing degrada- tion of lipofuscin, and thereby suppress senescence of cardiomyocytes.”
“Lower dose (50% dose producing immunosuppressive drug level) of rapamycin can attenuate progressive ventricular dysfunction and remodeling in heart failure [42]. 14 ppm rapamycin is effective for anti-aging [22,28]. Thus, lower dose of the microencapsulated rapamycin may apply in alleviating lipofuscin accumulation and senescence of cardiomyocytes. Notably, rapamycin should be administered in short time to avoid its undesirable side effects.”
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