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Systematic review
Epigenetic clocks in neurodegenerative diseases: a systematic review
  1. Tianmi Yang,
  2. Yi Xiao,
  3. Yangfan Cheng,
  4. Jingxuan Huang,
  5. Qianqian Wei,
  6. Chunyu Li,
  7. Huifang Shang
  1. Department of Neurology, Sichuan University, Chengdu, Sichuan, China
  1. Correspondence to Professor Huifang Shang, Department of Neurology, Sichuan University, Chengdu, Sichuan 610041, China; hfshang2002{at}


Background Biological ageing is one of the principal risk factors for neurodegenerative diseases. It is becoming increasingly clear that acceleration of DNA methylation age, as measured by the epigenetic clock, is closely associated with many age-related diseases.

Methods We searched the PubMed and Web of Science databases to identify eligible studies reporting epigenetic clocks in several neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS) and Huntington’s disease (HD).

Results Twenty-three studies (12 for AD, 4 for PD, 5 for ALS, and 2 for HD) were included. We systematically summarised the clinical utility of 11 epigenetic clocks (based on blood and brain tissues) in assessing the risk factors, age of onset, diagnosis, progression, prognosis and pathology of AD, PD, ALS and HD. We also critically described our current understandings to these evidences, and further discussed key challenges, potential mechanisms and future perspectives of epigenetic ageing in neurodegenerative diseases.

Conclusions Epigenetic clocks hold great potential in neurodegenerative diseases. Further research is encouraged to evaluate the clinical utility and promote the application.

PROSPERO registration number CRD42022365233.

Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as supplementary information.

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  • Contributors TY and HS contributed to the study conception and design. TY and YX performed the literature search and data collection. TY wrote the first draft of the manuscript. TY, HS, YX, YC, JH, QW and CL read, edited and approved the final manuscript. HS was responsible for the overall content as guarantor.

  • Funding This study was supported by the National Natural Science Foundation of China (grant no. 81871000) and Sichuan Science and Technology Programme (grant no. 2022ZDZX0023).

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.