Cell aging attenuates cellular functions, resulting in time-dependent disruption of cellular homeostasis, which maintains the functions of proteins and organelles. Mitochondria are important organelles responsible for cellular energy production and various metabolic processes, and their dysfunction is strongly related to the progression of cellular aging. Here we demonstrate that disruption of proteostasis attenuates mitochondrial function before the induction of DNA damage signaling by proliferative and replicative cellular aging. We found that lotus (Nelumbo nucifera Gaertn.) germ extract clears abnormal proteins and agglutinates via autophagy-mediated restoration of mitochondrial function and cellular aging phenotypes. Pharmacological analyses revealed that DAPK1 expression was suppressed in aging cells, and lotus germ extract upregulated DAPK1 expression by stimulating the acetylation of histones and then induced autophagy by activating the DAPK1-Beclin1 signaling pathway. Furthermore, treatment of aging fibroblasts with lotus germ extract stimulated collagen production and increased contractile ability in three-dimensional cell culture. Thus, time-dependent accumulation of abnormal proteins and agglutinates suppressed mitochondrial function in cells in the early stage of aging, and reactivation of mitochondrial function by restoring proteostasis rejuvenated aging cells. Lotus germ extract rejuvenates aging fibroblasts via the DAPK1-Beclin1 pathway-induced autophagy to clear abnormal proteins and agglutinates.

中文翻译：

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莲胚提取物通过诱导自噬恢复破坏的蛋白质稳态，使衰老的成纤维细胞恢复活力

细胞老化减弱细胞功能，导致细胞稳态随时间的破坏，从而维持蛋白质和细胞器的功能。线粒体是负责细胞能量产生和各种代谢过程的重要细胞器，其功能障碍与细胞衰老的进展密切相关。在这里，我们证明在通过增殖和复制细胞老化诱导 DNA 损伤信号之前，蛋白质稳态的破坏减弱了线粒体功能。我们发现了莲花（Nelumbo nuciferaGaertn.) 胚芽提取物清除异常蛋白质并通过自噬介导的线粒体功能恢复和细胞老化表型凝集。药理学分析表明，DAPK1 表达在衰老细胞中受到抑制，莲胚提取物通过刺激组蛋白乙酰化上调 DAPK1 表达，然后通过激活 DAPK1-Beclin1 信号通路诱导自噬。此外，在三维细胞培养中，用莲胚提取物处理老化的成纤维细胞可刺激胶原蛋白的产生并增强收缩能力。因此，异常蛋白质和凝集物的时间依赖性积累会抑制衰老早期细胞中的线粒体功能，而通过恢复蛋白质稳态来重新激活线粒体功能可以使衰老细胞恢复活力。