Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans

  • McColl G
  • Killilea D
  • Hubbard A
 et al. 
  • 88


    Mendeley users who have this article in their library.
  • 100


    Citations of this article.


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.

Get free article suggestions today

Mendeley saves you time finding and organizing research

Sign up here
Already have an account ?Sign in

Find this document


  • David KillileaUniversity of California San Francisco

  • Gawain McColl

  • Alan E. Hubbard

  • Maithili C. Vantipalli

  • Simon Melov

  • Gordon J. Lithgow

Cite this document

Choose a citation style from the tabs below

Save time finding and organizing research with Mendeley

Sign up for free