Journal
CELL REPORTS
Volume 15, Issue 3, Pages 638-650Publisher
CELL PRESS
DOI: 10.1016/j.celrep.2016.03.041
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Funding
- UCL Scholarships
- Max Planck Society
- European Research Council
- Research Into Ageing
- Wellcome Trust
- Parkinson's UK
- Alzheimer's Research UK
- Alzheimers Research UK [ART-PG2009-4] Funding Source: researchfish
- Parkinson's UK [H-1105] Funding Source: researchfish
- Wellcome Trust [098565/Z/12/Z] Funding Source: researchfish
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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 lifeextending 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.
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