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