Pharmacogenetic analysis of lithium-induced delayed aging in Caenorhabditis elegans

被引：155

作者：

McColl, Gawain ^{[1
]}

Killilea, David W. ^{[2
]}

Hubbard, Alan E. ^{[3
]}

Vantipalli, Maithili C. ^{[1
]}

Melov, Simon ^{[1
]}

Lithgow, Gordon J. ^{[1
]}

机构：

[1] Buck Inst Age Res, Novato, CA 94945 USA

[2] Childrens Hosp Oakland, Res Inst, Ctr Nutr & Metabol, Oakland, CA 94609 USA

[3] Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA

来源：

JOURNAL OF BIOLOGICAL CHEMISTRY | 2008年 / 283卷 / 01期

关键词：

D O I：

10.1074/jbc.M705028200

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (similar to 25% median increase), suggesting Li+ regulates survival by modulating histone methylation and chromatin structure.

引用

页码：350 / 357

页数：8

共 61 条

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