Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts

Naoki Makino, Jun ichi Oyama, Toyoki Maeda, Masamichi Koyanagi, Yoshihiro Higuchi, Keiko Tsuchida

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Abstract

The aims of this study were to investigate the impact of caloric restriction (CR) on cardiac telomere biology in an animal model of diabetes and to examine the signal transduction involved in cell senescence as well as cardiac function. Male 8-week-old Otsuka Long-Evans Tokushima fatty (OLETF) diabetic rats were divided into two groups: a group fed ad libitum (OLETF-AL) and a group fed with CR (OLETF-CR: 30 % energy reduction). Long-Evans Tokushima Otsuka (LETO) non-diabetic rats were used as controls. LETO rats were also divided into two groups: a CR (LETO-CR) group and a group fed AL (LETO-AL). At 40 weeks of age, the body weight was decreased by 9.7 % and the insulin resistance was less in OLETF-CR rats. Telomerase activity in OLETF-CR rats was significantly increased, and telomerase reverse transcriptase was more highly expressed in those rats. However, the telomere length (TL) was not different between AL- and CR-treated rats of each strain. The protein expressions for FoxO1 and FoxO3 were increased in OLETF-AL rats, but the levels of phosphorylated (p)-Akt were decreased compared to those in OLETF-CR rats. Autophagic LC3II signals revealed significant increases in OLETF-CR rats. Echocardiography showed that OLETF-CR improved the left ventricular diastolic dysfunction without changes in the left ventricular dimension. This study revealed that CR increases cardiac telomerase activity without TL attrition, and significantly ameliorates diastolic dysfunction. These findings suggest that cardiac telomerase activity may play an important role in the maintenance of normal cardiac function.

Original languageEnglish
JournalMolecular and cellular biochemistry
Volume403
Issue number1-2
DOIs
Publication statusPublished - May 1 2015

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Caloric Restriction
Telomerase
Autophagy
Rats
Inbred OLETF Rats
Telomere
Echocardiography
Signal transduction
Cell Aging
Left Ventricular Dysfunction
Medical problems
Insulin Resistance
Signal Transduction
Animals
Animal Models

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Calorie restriction increases telomerase activity, enhances autophagy, and improves diastolic dysfunction in diabetic rat hearts. / Makino, Naoki; Oyama, Jun ichi; Maeda, Toyoki; Koyanagi, Masamichi; Higuchi, Yoshihiro; Tsuchida, Keiko.

In: Molecular and cellular biochemistry, Vol. 403, No. 1-2, 01.05.2015.

Research output: Contribution to journalArticle

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