4.6 Article

Lotus germ extract rejuvenates aging fibroblasts via restoration of disrupted proteostasis by the induction of autopnagy

期刊

AGING-US
卷 14, 期 19, 页码 7662-7691

出版社

IMPACT JOURNALS LLC
DOI: 10.18632/aging.204303

关键词

mitochondria; autophagy; proteostasis; aging

资金

  1. JSPS [19K07045]
  2. Takeda science foundation
  3. Uehara memorial foundation
  4. Nakashima foundation
  5. Nakatomi foundation

向作者/读者索取更多资源

Cell aging leads to reduced cellular functions and disruption of cellular homeostasis, with mitochondrial dysfunction playing a crucial role. The study demonstrates that lotus germ extract can rejuvenate aging fibroblasts by restoring mitochondrial function and clearing abnormal proteins.
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 mitochondria! 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 mitochondria! function in cells in the early stage of aging, and reactivation of mitochondria! function by restoring proteostasis rejuvenated aging cells. Lotus germ extract rejuvenates aging fibroblasts via the DAPK1-Beclinl pathway-induced autophagy to clear abnormal proteins and agglutinates.

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