Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

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

doi:10.1016/j.celrep.2016.03.041

Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis

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

Authors

Jorge�Iv�n Castillo-Quan

Li Li

Kerri�J Kinghorn

Dobril�K Ivanov

Luke�S Tain

Cathy Slack

Dr Fiona Kerr F.Kerr@napier.ac.uk
Lecturer

Tobias Nespital

Janet Thornton

John Hardy

Ivana Bjedov

Linda Partridge

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.

Citation

Castillo-Quan, J., Li, L., Kinghorn, K., Ivanov, D., Tain, L., Slack, C., …Partridge, L. (2016). Lithium Promotes Longevity through GSK3/NRF2-Dependent Hormesis. Cell Reports, 15(3), 638-650. https://doi.org/10.1016/j.celrep.2016.03.041

Journal Article Type	Article
Acceptance Date	Mar 10, 2016
Online Publication Date	Apr 7, 2016
Publication Date	Apr 19, 2016
Deposit Date	Aug 19, 2016
Publicly Available Date	Aug 19, 2016
Journal	Cell Reports
Print ISSN	2211-1247
Electronic ISSN	2211-1247
Publisher	Elsevier
Peer Reviewed	Peer Reviewed
Volume	15
Issue	3
Pages	638-650
DOI	https://doi.org/10.1016/j.celrep.2016.03.041
Keywords	GSK-3; Keap1; NRF-2; aging; dietary restriction; triglycerides; xenobiotic stress;
Public URL	http://researchrepository.napier.ac.uk/Output/355663