期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 283, 期 1, 页码 350-357出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M705028200
关键词
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资金
- NIA NIH HHS [R01 AG021069, R01 AG022868-02, R01 AG021069-05, R01 AG022868-05, P30 AG 025708, R01 AG022868-04, AG 21069, R01 AG021069-04, P30 AG025708, AG 22868, R01 AG022868-01, R01 AG021069-01, R01 AG022868, R01 AG021069-03, R01 AG022868-03, R01 AG021069-02, R01 AG018679, R01 AG024385] Funding Source: Medline
- NINDS NIH HHS [R03 NS050789, NS 050789-01] Funding Source: Medline
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.
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