FoxO1 signaling plays a pivotal role in the cardiac telomere biology responses to calorie restrictionReport as inadecuate

FoxO1 signaling plays a pivotal role in the cardiac telomere biology responses to calorie restriction - Download this document for free, or read online. Document in PDF available to download.

Molecular and Cellular Biochemistry

, Volume 412, Issue 1–2, pp 119–130

First Online: 26 December 2015Received: 17 September 2015Accepted: 08 December 2015DOI: 10.1007-s11010-015-2615-8

Cite this article as: Makino, N., Oyama, J., Maeda, T. et al. Mol Cell Biochem 2016 412: 119. doi:10.1007-s11010-015-2615-8


This study examined whether the forkhead transcription factors of O group 1 FoxO1 might be involved in telomere biology during calorie restriction CR. We used FoxO1-knockout heterozygous mice FoxO1 and wild-type mice WT as a control. Both WT and FoxO1 were subjected to ad libitum AL feeding or 30 % CR compared to AL for 20 weeks from 15 weeks of age. The heart-to-body weight ratio, blood glucose, and serum lipid profiles were not different among all groups of mice at the end of the study. Telomere size was significantly lower in the FoxO1-AL than the WT-AL, and telomere attrition was not observed in either WT-CR or FoxO1-CR. Telomerase activity was elevated in the heart and liver of WT-CR, but not in those of FoxO1-CR. The phosphorylation of Akt was inhibited and Sirt 1 was activated in heart tissues of WT-CR and FoxO1-CR. However, the ratio of conjugated to cytosolic light chain 3 increased and the level of p62 decreased in WT-CR, but not in FoxO1-CR. A marker of oxidative DNA damage, 8-OhdG, was significantly lower in WT-CR only. The level of MnSOD and eNOS increased, and the level of cleaved caspase-3 decreased in WT-CR, but not FoxO1-CR. Echocardiography showed that the left ventricular end-diastolic and systolic dimensions were significantly lower in WT-CR or FoxO1-CR than WT-AL or FoxO1-AL, respectively. The present studies suggest that FoxO1 plays beneficial roles by inducing genes involved in telomerase activity, as well as anti-oxidant, autophagic, and anti-apoptotic genes under conditions of CR, and suggest that FoxO1 signaling may be an important mediator of metabolic equilibrium during CR.

KeywordsCalorie restriction FoxO1 Telomere Telomerase Autophagy Oxidative stress  Download fulltext PDF

Author: N. Makino - J. Oyama - T. Maeda - M. Koyanagi - Y. Higuchi - I. Shimokawa - N. Mori - T. Furuyama


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