title: FoxO1 signaling plays a pivotal role in the cardiac telomere biology responses to calorie restriction.
abstract: 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.
authors.affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan. makino0108@gmail.com.
authors.forename: N
authors.initials: N
authors.lastname: Makino
authors.affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Oyama
authors.affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Maeda
authors.affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Koyanagi
authors.affiliation: Division of Molecular and Clinical Gerontology, Department of Molecular and Cellular Biology, Medical Institute of Bioregulation, Kyushu University, 4546 Tsurumihara, Beppu, 874-0838, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Higuchi
authors.affiliation: Department of Investigative Pathology, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: I
authors.initials: I
authors.lastname: Shimokawa
authors.affiliation: Department of Anatomy and Neurobiology, Nagasaki University School of Medicine, Nagasaki, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Mori
authors.affiliation: Department of Liberal Arts and Sciences, Kagawa Prefectural College of Health Sciences, Kagawa, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Furuyama
mesh_terms: D000818:Animals; D001835:Body Weight; D031204:Caloric Restriction; D053148:Caspase 3 / Q000378:metabolism; D004249:DNA Damage; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D009206:Myocardium / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D009929:Organ Size; D018384:Oxidative Stress; D015398:Signal Transduction; D013482:Superoxide Dismutase / Q000378:metabolism; D016615:Telomere
chemical_list: D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D052250:Nitric Oxide Synthase Type III; D013482:Superoxide Dismutase; D053148:Caspase 3
keywords: Autophagy; Calorie restriction; FoxO1; Oxidative stress; Telomerase; Telomere