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Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate

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Abstract

Ferulate (4-hydroxy-3-methoxycinnamic acid) is a well-known phenolic compound that scavenges free radicals and exerts anti-inflammatory effects. Forkhead box O3a (FOXO3a), a transcription factor that plays important roles in aging processes, decreases with age and is negatively regulated through phosphorylation by phosphatidylinositol 3-kinase (PI3K)/Akt signaling. The present study investigated the efficacy of short-term ferulate feeding on age-related changes in PI3K/Akt/FOXO3a and upstream insulin signaling pathways in aged rats. In addition, changes in manganese superoxide dismutase (MnSOD) and catalase expression were examined because of their dependence on PI3K/Akt/FOXO3a activity. Short-term feeding experiments were done with a diet containing ferulate that was given to aged rats at doses of 3 or 6 mg kg−1 day−1 for 10 days. Results showed that FOXO3a activity was increased in the ferulate-fed old group compared with the control old group. Also, ferulate suppressed the PI3K/Akt signaling pathway that is responsible for FOXO3a inhibition in aged rats. Plasma insulin levels and the upstream insulin signaling pathway were also modulated by ferulate correspondingly with PI3K/Akt/FOXO3a activity. The age-related decrease in two major antioxidant enzymes, MnSOD and catalase, was blunted by ferulate, which was accompanied by FOXO3a transcriptional activity. The significance of the present study is the finding that short-term feeding of ferulate effectively modulates age-related renal FOXO3a, PI3K/Akt and insulin signaling pathways, and MnSOD and catalase expression, all of which may be beneficial for attenuating the aging process.

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Acknowledgments

This work was supported by a National Research Foundation of Korea (NRF) grant funded by the Korea government (MEST, no. 2009-0083538). We thank the Aging Tissue Bank for supplying research information.

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Authors and Affiliations

  1. Department of Pharmacy, College of Pharmacy, Pusan National University, San 30, JangJeon-dong, GeumJeong-gu, Busan, 609-735, South Korea

    Yeon Ja Choi, Dae Hyun Kim, Eun Kyeong Lee, Ji Min Kim, Young Mi Ha, Nam Deuk Kim, Jee H. Jung & Hae Young Chung

  2. Molecular Inflammation Research Center for Aging Intervention (MRCA), Pusan National University, Busan, 609-735, South Korea

    Yeon Ja Choi, Ji Min Kim, Young Mi Ha, Nam Deuk Kim, Jee H. Jung & Hae Young Chung

  3. Faculty of Food Science and Biotechnology, Pukyong National University, Nam-gu, Busan, 608-737, South Korea

    Jae Sue Choi

  4. Department of Physiology, The University of Texas Health Science Center at San Antonio, San Antonio, TX, 78229-3900, USA

    Byung Pal Yu

  5. Research Center, Dongnam Institute of Radiological and Medical Sciences, Busan, 619-953, Republic of Korea

    Eun Kyeong Lee

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  1. Yeon Ja Choi
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Correspondence to Hae Young Chung.

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Choi, Y.J., Kim, D.H., Lee, E.K. et al. Attenuation of age-related changes in FOXO3a activity and the PI3K/Akt pathway by short-term feeding of ferulate. AGE 34, 317–327 (2012). https://doi.org/10.1007/s11357-011-9235-3

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