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J Biol Chem. 2008 Jan 4;283(1):350-7. Epub 2007 Oct 24.

Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans.

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Buck Institute for Age Research, Novato, CA 94945, USA.


Lithium (Li(+)) has been used to treat mood affect disorders, including bipolar, for decades. This drug is neuroprotective and has several identified molecular targets. However, it has a narrow therapeutic range and the one or more underlying mechanisms of its therapeutic action are not understood. Here we describe a pharmacogenetic study of Li(+) in the nematode Caenorhabditis elegans. Exposure to Li(+) at clinically relevant concentrations throughout adulthood increases survival during normal aging (up to 46% median increase). Longevity is extended via a novel mechanism with altered expression of genes encoding nucleosome-associated functions. Li(+) treatment results in reduced expression of the worm ortholog of LSD-1 (T08D10.2), a histone demethylase; knockdown by RNA interference of T08D10.2 is sufficient to extend longevity ( approximately 25% median increase), suggesting Li(+) regulates survival by modulating histone methylation and chromatin structure.

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