한빛사논문
- 조회1,684
아모레퍼시픽
Sugyun Ana,1, Si-Young Chob,1, Junsoo Kanga, Soobeom Leea, Hyung-Su Kimb, Dae-Jin Minb, EuiDong Sonb, and Kwang-Hyun Choa,2
aDepartment of Bio and Brain Engineering, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea; and bR&D Unit, Amorepacific Corporation, 17074 Gyeonggi-do, Republic of Korea
1S.A. and S.-Y.C. contributed equally to this work.
2To whom correspondence may be addressed.
Abstract
Cellular senescence is defined as a stable, persistent arrest of cell proliferation. Here, we examine whether senescent cells can lose senescence hallmarks and reenter a reversible state of cell-cycle arrest (quiescence). We constructed a molecular regulatory network of cellular senescence based on previous experimental evidence. To infer the regulatory logic of the network, we performed phosphoprotein array experiments with normal human dermal fibroblasts and used the data to optimize the regulatory relationships between molecules with an evolutionary algorithm. From ensemble analysis of network models, we identified 3-phosphoinositide–dependent protein kinase 1 (PDK1) as a promising target for inhibitors to convert the senescent state to the quiescent state. We showed that inhibition of PDK1 in senescent human dermal fibroblasts eradicates senescence hallmarks and restores entry into the cell cycle by suppressing both nuclear factor κB and mTOR signaling, resulting in restored skin regeneration capacity. Our findings provide insight into a potential therapeutic strategy to treat age-related diseases associated with the accumulation of senescent cells.
cellular senescence, systems biology, network modeling, PDK1, skin aging
논문정보
TOP52020년 선정
- Research article
- 2020년 11월 (BRIC 등록일 2020-11-30)
- 국내 연구진
- 생명과학 > 생물공학
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