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Lithium promotes longevity through GSK3/NRF2-dependent hormesis
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Castillo-Quan, Jorge Iván, Li, Li, Kinghorn, Kerri J., Ivanov, Dobril K., Tain, Luke S., Slack, Cathy, Kerr, Fiona, Nespital, Tobias, Thornton, Janet, Hardy, John, Bjedov, Ivana and Partridge, Linda (2016) Lithium promotes longevity through GSK3/NRF2-dependent hormesis. Cell Reports, 15 (3). pp. 638-650. doi:10.1016/j.celrep.2016.03.041 ISSN 2211-1247.
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Official URL: http://doi.org/10.1016/j.celrep.2016.03.041
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.
Item Type: | Journal Article | ||||||||||||||||||||||||
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Subjects: | R Medicine > RC Internal medicine | ||||||||||||||||||||||||
Divisions: | Faculty of Science, Engineering and Medicine > Science > Life Sciences (2010- ) | ||||||||||||||||||||||||
Library of Congress Subject Headings (LCSH): | Lithium -- Therapeutic use, Bipolar disorder -- Chemotherapy, Cell physiology, Glycogen synthase kinase-3, Drosophila -- Aging | ||||||||||||||||||||||||
Journal or Publication Title: | Cell Reports | ||||||||||||||||||||||||
Publisher: | Elsevier Inc. | ||||||||||||||||||||||||
ISSN: | 2211-1247 | ||||||||||||||||||||||||
Official Date: | 19 April 2016 | ||||||||||||||||||||||||
Dates: |
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Volume: | 15 | ||||||||||||||||||||||||
Number: | 3 | ||||||||||||||||||||||||
Page Range: | pp. 638-650 | ||||||||||||||||||||||||
DOI: | 10.1016/j.celrep.2016.03.041 | ||||||||||||||||||||||||
Status: | Peer Reviewed | ||||||||||||||||||||||||
Publication Status: | Published | ||||||||||||||||||||||||
Access rights to Published version: | Open Access (Creative Commons) | ||||||||||||||||||||||||
Date of first compliant deposit: | 18 May 2023 | ||||||||||||||||||||||||
Date of first compliant Open Access: | 18 May 2023 | ||||||||||||||||||||||||
RIOXX Funder/Project Grant: |
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