TY - JOUR
T1 - Integrative epigenomic and transcriptomic analyses reveal metabolic switching by intermittent fasting in brain
AU - Ng, Gavin Yong Quan
AU - Sheng, Dominic Paul Lee Kok
AU - Bae, Han Gyu
AU - Kang, Sung Wook
AU - Fann, David Yang Wei
AU - Park, Jinsu
AU - Kim, Joonki
AU - Alli-Shaik, Asfa
AU - Lee, Jeongmi
AU - Kim, Eunae
AU - Park, Sunyoung
AU - Han, Jeung Whan
AU - Karamyan, Vardan
AU - Okun, Eitan
AU - Dheen, Thameem
AU - Hande, Manoor Prakash
AU - Vemuganti, Raghu
AU - Mallilankaraman, Karthik
AU - Lim, Lina H.K.
AU - Kennedy, Brian K.
AU - Drummond, Grant R.
AU - Sobey, Christopher G.
AU - Gunaratne, Jayantha
AU - Mattson, Mark P.
AU - Foo, Roger Sik Yin
AU - Jo, Dong Gyu
AU - Arumugam, Thiruma V.
N1 - Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Aging Association.
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Cerebellum
KW - Epigenetics
KW - Intermittent fasting
KW - Metabolism
KW - Transcriptomics
UR - https://www.scopus.com/pages/publications/85127524684
U2 - 10.1007/s11357-022-00537-z
DO - 10.1007/s11357-022-00537-z
M3 - Article
C2 - 35357643
AN - SCOPUS:85127524684
SN - 2509-2715
VL - 44
SP - 2171
EP - 2194
JO - GeroScience
JF - GeroScience
IS - 4
ER -