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Cited by 46Epigenetics and DNA MethylationPhysical Activity and HealthDementia and Cognitive Impairment Research

Roles of physical exercise in neurodegeneration: reversal of epigenetic clock

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Xu, Miao, Zhu, JiaYi, Liu, Xian-Dong, Luo, Ming-Ying, Xu, Nan-Jie·2021·Translational Neurodegeneration
DOI 10.1186/s40035-021-00254-1PMC PMC8361623
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Abstract

The epigenetic clock is defined by the DNA methylation (DNAm) level and has been extensively applied to distinguish biological age from chronological age. Aging-related neurodegeneration is associated with epigenetic alteration, which determines the status of diseases. In recent years, extensive research has shown that physical exercise (PE) can affect the DNAm level, implying a reversal of the epigenetic clock in neurodegeneration. PE also regulates brain plasticity, neuroinflammation, and molecular signaling cascades associated with epigenetics. This review summarizes the effects of PE on neurodegenerative diseases via both general and disease-specific DNAm mechanisms, and discusses epigenetic modifications that alleviate the pathological symptoms of these diseases. This may lead to probing of the underpinnings of neurodegenerative disorders and provide valuable therapeutic references for cognitive and motor dysfunction.

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  • Reversal of epigenetic clock is reported to be an underlying mechanism.

    “Reversal of epigenetic clock is reported to be an underlying mechanism.128”

    From Role of neuroinflammation in neurodegeneration development (2023) · cites this paper as [128]

    The Background (page unavailable) says physical exercise has the potential to reverse the epigenetic clock in neurodegeneration, and the Abstract says exercise-related DNA methylation changes imply such a reversal. These passages support the proposed link, but do not establish clock reversal as an underlying mechanism. (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Lifestyle interventions can improve or maintain quality of life, slow cognitive decline, and even mitigate epigenetic age acceleration.

    “lifestyle interventions can improve or maintain quality of life (QoL), slow cognitive decline, and even mitigate epigenetic age acceleration [7-9]”

    From Toward a Smartphone-Based and Conversational Agent–Delivered Just-in-Time Adaptive Holistic Lifestyle Intervention for Older Adults Affected by Cognitive Decline: Two-Week Proof-of-Concept Study (2025) · cites this paper as [7]

    The Background (page unavailable) says physical exercise can help prevent or alleviate cognitive decline and describes its potential to slow epigenetic age acceleration. The paper focuses on exercise rather than lifestyle interventions generally, and the passages found do not address improving or maintaining quality of life (searched: “quality of life”). (LLM, conf=0.86)

    Experimental — accuracy not yet measured

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Authors
Xu, M., Zhu, J., Liu, X.-D., Luo, M.-Y., & Xu, N.-J.
Affiliations
Shanghai Jiao Tong University (CN)
Corresponding author
Xu, Nan-Jie
ORCID
Venue
Translational Neurodegeneration
Publisher
Springer Science and Business Media LLC
Published
2021-08-13
Volume
10
Issue
1
Pages
30-30
ISSN
2047-9158 (ISSN-L)
DOI
10.1186/s40035-021-00254-1
PMC
PMC8361623
OpenAlex
W3188694691
Cited by
46
References
172
Citations by year
2026: 4 · 2025: 12 · 2024: 10 · 2023: 13 · 2022: 4 · 2021: 3
FWCI
0.79
Type
journal article
Language
en
Open access
Licence
Locations
  • Translational Neurodegeneration (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • TSpace (University of Toronto) (submittedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Natural Science Foundation of China (31671062, 81870820, 31900796)
  • Science and Technology Commission of Shanghai Municipality (16JC1420500, 18JC1420302)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Health Sciences › Medicine › Physiology › Physical Activity and Health
  • Health Sciences › Medicine › Psychiatry and Mental health › Dementia and Cognitive Impairment Research
Keywords
physical activity, neurodegeneration, epigenetic clocks, DNA methylation, biological age, aging, neuroplasticity, neuroinflammation, epigenetic modifications, neurodegenerative diseases, cognitive impairment, motor impairment
MeSH terms
Aging, Brain, DNA Damage, Humans, Exercise, DNA Methylation, Neurodegenerative Diseases, Epigenesis, Genetic

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