Evidence mapPaperPMID 42229233Full record

ArticleRedox biology2026

CHK1 activates mitophagy to attenuate cardiac aging via inhibiting AHSA1-ubiquitination.

Peng Jing, Liu-Hua Zhou, Shu-Xuan Chen, Jia-Yi Chen, Ling-Feng Gu, Tong-Tong Yang, Si-Bo Wang, Chong Du, Yi-Xi Chen, Qi-Ming Wang and 2 more

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Article in Redox biology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

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2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

12 authors.

Peng JingDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Liu-Hua ZhouDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Shu-Xuan ChenDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Jia-Yi ChenDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Ling-Feng GuDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Tong-Tong YangDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Si-Bo WangDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Chong DuDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Yi-Xi ChenDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China.
Qi-Ming WangDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China. Electronic address: wangqiming@jsph.org.cn.
Lian-Sheng WangDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China. Electronic address: drlswang@njmu.edu.cn.
Hao WangDepartment of Cardiology, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, China. Electronic address: wanghaonjmu@163.com.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

With the acceleration of global population aging, the progressive deterioration of cardiac structure and function has become a critical determinant of cardiovascular health, presenting a significant public health challenge. Checkpoint kinase 1 (CHK1), a key cell cycle checkpoint protein, plays an essential role in various biological processes by mediating signaling cascades. While CHK1 has been shown to be important for heart regeneration, its role in the aging process of the heart remains unclear. In this study, we investigated the alterations in CHK1 expression in aging hearts and elucidated the underlying regulatory mechanisms. In both in vivo and in vitro models, CHK1 expression was significantly downregulated during aging. To assess its functional role, we generated cardiomyocyte-specific CHK1 overexpression and knockout mice and compared their cardiac performance. We found that CHK1 overexpression alleviated age-associated cardiac dysfunction, while CHK1 knockout worsened cardiac function in aged mice. Furthermore, CHK1 overexpression significantly attenuated doxorubicin (DOX)-induced acutely senescence in adult mouse cardiomyocytes (AMCMs) and human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs). Mechanistic studies revealed that CHK1 overexpression delayed cardiac aging by activating heat shock protein 90 (HSP90)-mediated mitophagy. Immunoprecipitation and mass spectrometry (IP-MS) analyses demonstrated that CHK1 directly interacts with the activator of HSP90 ATPase homolog 1 (AHSA1), thereby suppressing TRIM8-mediated ubiquitination and degradation, facilitating AHSA1-HSP90 complex formation, and enhancing HSP90 ATPase activity. Overall, our results suggest that CHK1 overexpression activates mitophagy via the AHSA1-HSP90 pathway to mitigate cardiac aging. This study highlights the critical role of CHK1 in cardiac aging and proposes a potential therapeutic strategy for aging-associated cardiomyopathy and heart failure.

Indexed as

AgingCheckpoint Kinase 1MitophagyAnimalsCellular SenescenceHSP90 Heat-Shock ProteinsHumansMiceMice, KnockoutMyocardiumMyocytes, CardiacSignal TransductionUbiquitinationCheckpoint Kinase 1CHEK1 protein, humanChek1 protein, mouseHSP90 Heat-Shock ProteinsAHSA1Cardiac agingCHK1HSP90Mitophagy

Identifiers

PMID42229233
PMCPMC13253101

What Socratic holds

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.