Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain

Gavin Yong Quan Ng, Dominic Paul Lee Kok Sheng, Han Gyu Bae, Sung Wook Kang, David Yang Wei Fann, Jinsu Park, Joonki Kim, Asfa Alli-Shaik, Jeongmi Lee, Eunae Kim, Sunyoung Park, Jeung Whan Han, Vardan Karamyan, Eitan Okun, Thameem Dheen, Manoor Prakash Hande, Raghu Vemuganti, Karthik Mallilankaraman, Lina H.K. Lim, Brian K. KennedyGrant R. Drummond, Christopher G. Sobey, Jayantha Gunaratne, Mark P. Mattson, Roger Sik Yin Foo, Dong Gyu Jo, Thiruma V. Arumugam

Research output: Contribution to journalArticlepeer-review

8 Scopus citations


Intermittent fasting (IF) remains the most effective intervention to achieve robust anti-aging effects and attenuation of age-related diseases in various species. Epigenetic modifications mediate the biological effects of several environmental factors on gene expression; however, no information is available on the effects of IF on the epigenome. Here, we first found that IF for 3 months caused modulation of H3K9 trimethylation (H3K9me3) in the cerebellum, which in turn orchestrated a plethora of transcriptomic changes involved in robust metabolic switching processes commonly observed during IF. Second, a portion of both the epigenomic and transcriptomic modulations induced by IF was remarkably preserved for at least 3 months post-IF refeeding, indicating that memory of IF-induced epigenetic changes was maintained. Notably, though, we found that termination of IF resulted in a loss of H3K9me3 regulation of the transcriptome. Collectively, our study characterizes the novel effects of IF on the epigenetic-transcriptomic axis, which controls myriad metabolic processes. The comprehensive analyses undertaken in this study reveal a molecular framework for understanding how IF impacts the metabolo-epigenetic axis of the brain and will serve as a valuable resource for future research.

Original languageEnglish
Pages (from-to)2171-2194
Number of pages24
Issue number4
Early online date31 Mar 2022
StatePublished - Aug 2022

Bibliographical note

Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Aging Association.


  • Cerebellum
  • Epigenetics
  • Intermittent fasting
  • Metabolism
  • Transcriptomics


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