Lithium promotes longevity through GSK3/NRF2-dependent hormesis

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.

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.

Publication DOI: https://doi.org/10.1016/j.celrep.2016.03.041
Divisions: Life & Health Sciences
Life & Health Sciences > Cell & Tissue Biomedical Research
Additional Information: © 2016 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
Uncontrolled Keywords: aging,dietary restriction,GSK-3,keap1,NRF-2,triglycerides,xenobiotic stress,Biochemistry, Genetics and Molecular Biology(all)
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Related URLs: http://www.scop ... tnerID=8YFLogxK (Scopus URL)
Published Date: 2016-04-19
Authors: Castillo-Quan, Jorge Iván
Li, Li
Kinghorn, Kerri J.
Ivanov, Dobril K.
Tain, Luke S.
Slack, Cathy ( 0000-0002-7949-4079)
Kerr, Fiona
Nespital, Tobias
Thornton, Janet
Hardy, John
Bjedov, Ivana
Partridge, Linda

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