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Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

Castillo-Quan, JI; Li, L; Kinghorn, KJ; Ivanov, DK; Tain, LS; Slack, C; Kerr, F; ... Partridge, L; + view all (2016) Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis. Cell Reports , 15 (3) pp. 638-650. 10.1016/j.celrep.2016.03.041. Green open access

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Abstract

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.

Type: Article
Title: Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1016/j.celrep.2016.03.041
Publisher version: http://dx.doi.org/10.1016/j.celrep.2016.03.041
Language: English
Additional information: Copyright © 2016 The Authors This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Keywords: GSK-3, Keap1, NRF-2, aging, dietary restriction, triglycerides, xenobiotic stress
UCL classification: UCL > Provost and Vice Provost Offices
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Life Sciences > Div of Biosciences > Genetics, Evolution and Environment
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Cancer Institute > Research Department of Cancer Bio
URI: http://discovery.ucl.ac.uk/id/eprint/1482409
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