• Open Access

Black tea polyphenols mimic insulin/insulin-like growth factor-1 signalling to the longevity factor FOXO1a

Authors

  • Amy R. Cameron,

    1. Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
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  • Siobhan Anton,

    1. Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
    2. Current address: Gentian AS, PO 733, 1509 Moss, Norway
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  • Laura Melville,

    1. Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
    2. Current address: MRC Human Reproductive Sciences Unit, University of Edinburgh, Edinburgh, Scotland
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  • Nicola P. Houston,

    1. Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
    2. Scottish Crop Research Institute, Invergowrie, Dundee, Scotland, DD2 5DA
    3. Current address: Institute of Structural Biology, School of Biological Sciences, Darwin Building, Kings Buildings, University of Edinburgh, Edinburgh, EH9 3JR, Scotland
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  • Saurabh Dayal,

    1. Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
    2. Current address: Division of Surgery and Molecular Oncology, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
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  • Gordon J. McDougall,

    1. Scottish Crop Research Institute, Invergowrie, Dundee, Scotland, DD2 5DA
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  • Derek Stewart,

    1. Scottish Crop Research Institute, Invergowrie, Dundee, Scotland, DD2 5DA
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  • Graham Rena

    1. Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY
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Graham Rena, Neurosciences Institute, Ninewells Hospital and Medical School, University of Dundee, Dundee, Scotland, DD1 9SY. Tel.: (01382) 660111 ext. 33126; fax: (01382) 667120); e-mail: g.rena@dundee.ac.uk

Summary

In vertebrates and invertebrates, relationships between diet and health are controlled by a conserved signalling pathway responsive to insulin-like ligands. In invertebrate models for example, forkhead transcription factor family O (FOXO) transcription factors in this pathway regulate the rate of aging in response to dietary cues, and in vertebrates, obesity and age-induced deficits in the same pathway are thought to contribute to dysregulation of hepatic gluconeogenesis through genes such as phosphoenolpyruvate carboxykinase (PEPCK). Recently, we have begun to screen for dietary constituents capable of regulating this pathway in our cell culture model. Here, we identify three black tea theaflavins, theaflavin 3-O-gallate, theaflavin 3′-O-gallate, theaflavin 3,3′di-O-gallate and thearubigins as novel mimics of insulin/IGF-1 action on mammalian FOXO1a, PEPCK and moreover we provide evidence that the effects on this pathway of the green tea constituent (-)-epigallocatechin gallate depend on its ability to be converted into these larger structures. With the exception of water, tea is the most popular drink globally, but despite this, little is known about the biological availability of black tea polyphenols in vivo or the molecular target(s) mediating the effects presented here. Further investigation in these two areas might provide insight into how age-related metabolic disease may be deferred.

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