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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review


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.

Original languageEnglish
Pages (from-to)638-650
Number of pages13
JournalCell Reports
Issue number3
Early online date7 Apr 2016
Publication statusPublished - 19 Apr 2016

Bibliographical note

© 2016 The Authors. This is an open access article under the CC BY license (


  • aging
  • dietary restriction
  • GSK-3
  • keap1
  • NRF-2
  • triglycerides
  • xenobiotic stress


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