Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

Jorge Iván Castillo-Quan; Li Li; Kerri J. Kinghorn; Dobril K. Ivanov; Luke S. Tain; Cathy Slack; Fiona Kerr; Tobias Nespital; Janet Thornton; John Hardy; Ivana Bjedov; Linda Partridge

doi:10.1016/j.celrep.2016.03.041

Cell Reports (Apr 2016)

Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

Jorge Iván Castillo-Quan,
Li Li,
Kerri J. Kinghorn,
Dobril K. Ivanov,
Luke S. Tain,
Cathy Slack,
Fiona Kerr,
Tobias Nespital,
Janet Thornton,
John Hardy,
Ivana Bjedov,
Linda Partridge

Affiliations

Jorge Iván Castillo-Quan: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
Li Li: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
Kerri J. Kinghorn: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
Dobril K. Ivanov: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
Luke S. Tain: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann Strasse 9-b, 50931 Köln, Germany
Cathy Slack: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
Fiona Kerr: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
Tobias Nespital: Max Planck Institute for Biology of Ageing, Joseph-Stelzmann Strasse 9-b, 50931 Köln, Germany
Janet Thornton: European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Wellcome Trust Genome Campus, Hinxton, Cambridge CB10 1SD, UK
John Hardy: Department of Molecular Neuroscience, Institute of Neurology, University College London, Queen Square, London WC1N 3BG, UK
Ivana Bjedov: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK
Linda Partridge: Institute of Healthy Ageing and Department of Genetics, Evolution and Environment, University College London, Darwin Building, Gower Street, London WC1E 6BT, UK

DOI: https://doi.org/10.1016/j.celrep.2016.03.041
Journal volume & issue: Vol. 15, no. 3
pp. 638 – 650

Abstract

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The quest to extend healthspan via pharmacological means is becoming increasingly urgent, both from a health and economic perspective. Here we show that lithium, a drug approved for human use, promotes longevity and healthspan. We demonstrate that lithium extends lifespan in female and male Drosophila, when administered throughout adulthood or only later in life. The life-extending mechanism involves the inhibition of glycogen synthase kinase-3 (GSK-3) and activation of the transcription factor nuclear factor erythroid 2-related factor (NRF-2). Combining genetic loss of the NRF-2 repressor Kelch-like ECH-associated protein 1 (Keap1) with lithium treatment revealed that high levels of NRF-2 activation conferred stress resistance, while low levels additionally promoted longevity. The discovery of GSK-3 as a therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life.

Published in Cell Reports

ISSN: 2211-1247 (Online)
Publisher: Elsevier
Country of publisher: Netherlands
LCC subjects: Science: Biology (General)
Website: http://www.cell.com/cell-reports/home

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