Work

Pharmacogenetic Analysis of Lithium-induced Delayed Aging in Caenorhabditis elegans

Year: 2007

Type: article

Abstract: 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.

Source: Journal of Biological Chemistry

DOI: 10.1074/jbc.m705028200

Authors: Gawain McColl, David W. Killilea, Alan E. Hubbard, Maithili C. Vantipalli, Simon Melov, Gordon J. Lithgow

Institutions: Buck Institute for Research on Aging, University of California, Berkeley

Language: English

Topic: Genetics, Aging, and Longevity in Model Organisms

Subfield: Aging

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,430