Lithium promotes longevity via GSK-3 and NRF-2 and is additive to other anti-aging interventions

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 new therapeutic target for aging will likely lead to more effective treatments that can modulate mammalian aging and further improve health in later life. The microarray experiment examines the transcriptional profiles of wild-type (w1118) vs. wild-type (w1118) + Lithium (LiCl, 10mM). Heads and thoraces from once mated females treated with vehicle or 10mM Li were snap frozen after 10d of treatment. RNA was Dnase treated and checked for quality by Biorad Experion. RNA was processed to cRNA, labeled and used for microarray analysis (GeneChip Drosophila Genome 2.0 Array), following manufacturer's protocol.

ORGANISM(S): Drosophila melanogaster

SUBMITTER: Dobril Ivanov 

PROVIDER: E-MTAB-3809 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress