Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice

Jul 3, 2015Brain research bulletin

Calorie restriction's impact on cell aging and growth pathways in old mice

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Abstract

Body weight and serum glucose in the calorie-restricted group were lower than in the high energy group after 44 weeks.

Caloric restriction increased the number of SIRT1-immunoreactive cells in the hippocampus compared to both normal and high energy groups.
SIRT1 mRNA expression was significantly higher in the caloric restriction group than in the high energy group.
No differences were observed in SIRT1 protein expression among the three dietary groups.
mTOR and S6K1 protein activation was significantly lower in the caloric restriction group compared to the normal control group.
Both mTOR and S6K1 mRNA levels were significantly reduced in the caloric restriction group relative to the normal control group.

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AIMS: To determine the effects and underlying molecular mechanisms of caloric restriction (CR) in C57BL/6 mice.

METHODS: Thirty-six 6-week-old male C57BL/6 mice were assigned to a normal control group (NC, n=12), a high energy group (HE, n=12), and a CR group (n=12), and received a normal diet, a high-calorie diet, or a calorie-restricted diet, respectively, for 44 weeks. Body weight and serum glucose concentration were regularly recorded, and animals were sacrificed and hippocampus tissues were collected for immunohistochemistry (n=6 per group), western blotting (n=3 per group) and real-time polymerase chain reaction (n=3 per group) analysis at the end of the 44-week experimental period. Immunohistochemistry, western blotting and real-time polymerase chain reaction were used to detect changes in hippocampal proteins may be involved in the SIRT1/mTOR pathways.

RESULTS: Body weight and serum glucose over the 44 weeks in animals from the CR group were lower than those of HE group. The number of SIRT1-immunoreactive cells in the CR group was significantly higher than in the NC and HE groups, and SIRT1 mRNA expression in the CR group was significantly higher than that in the HE group, but there was no difference in SIRT1 protein expression among the three groups. mTOR and S6K1 protein activation and mTOR and S6K1 mRNA were significantly lower in the CR group than in the NC group.

CONCLUSIONS: Our findings suggest that a CR diet could lead to activation of SIRT1 and suppression of mTOR and S6K1 activation in C57BL/6 mice. We have shown that the SIRT1/mTOR signaling pathways may be involved in the neuroprotective effect of CR.

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Effect of caloric restriction on the SIRT1/mTOR signaling pathways in senile mice

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