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Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus

Author

Listed:
  • Sara Zocher

    (German Center for Neurodegenerative Diseases (DZNE) Dresden
    Technische Universität Dresden)

  • Rupert W. Overall

    (German Center for Neurodegenerative Diseases (DZNE) Dresden
    Technische Universität Dresden)

  • Mathias Lesche

    (Technische Universität Dresden
    Technische Universität Dresden)

  • Andreas Dahl

    (Technische Universität Dresden
    Technische Universität Dresden)

  • Gerd Kempermann

    (German Center for Neurodegenerative Diseases (DZNE) Dresden
    Technische Universität Dresden)

Abstract

The decline of brain function during aging is associated with epigenetic changes, including DNA methylation. Lifestyle interventions can improve brain function during aging, but their influence on age-related epigenetic changes is unknown. Using genome-wide DNA methylation sequencing, we here show that experiencing a stimulus-rich environment counteracts age-related DNA methylation changes in the hippocampal dentate gyrus of mice. Specifically, environmental enrichment prevented the aging-induced CpG hypomethylation at target sites of the methyl-CpG-binding protein Mecp2, which is critical to neuronal function. The genes at which environmental enrichment counteracted aging effects have described roles in neuronal plasticity, neuronal cell communication and adult hippocampal neurogenesis and are dysregulated with age-related cognitive decline in the human brain. Our results highlight the stimulating effects of environmental enrichment on hippocampal plasticity at the level of DNA methylation and give molecular insights into the specific aspects of brain aging that can be counteracted by lifestyle interventions.

Suggested Citation

  • Sara Zocher & Rupert W. Overall & Mathias Lesche & Andreas Dahl & Gerd Kempermann, 2021. "Environmental enrichment preserves a young DNA methylation landscape in the aged mouse hippocampus," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    • Handle: RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-23993-1
    DOI: 10.1038/s41467-021-23993-1
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    Cited by:

    1. Raúl F. Pérez & Patricia Tezanos & Alfonso Peñarroya & Alejandro González-Ramón & Rocío G. Urdinguio & Javier Gancedo-Verdejo & Juan Ramón Tejedor & Pablo Santamarina-Ojeda & Juan José Alba-Linares & , 2024. "A multiomic atlas of the aging hippocampus reveals molecular changes in response to environmental enrichment," Nature Communications, Nature, vol. 15(1), pages 1-26, December.
    2. Salman Sadullah Usmani & Hyun-Gug Jung & Qichao Zhang & Min Woo Kim & Yuna Choi & Ahmet Burak Caglayan & Dongsheng Cai, 2024. "Targeting the hypothalamus for modeling age-related DNA methylation and developing OXT-GnRH combinational therapy against Alzheimer’s disease-like pathologies in male mouse model," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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