Rapamycin and Ageing: When, for How Long, and How Much?
The mechanistic target of rapamycin (mTOR) is a nutrient and growth factor responsive kinase that modulates lifespan in species from yeast to mice (Johnson et al.,2013b).mTOR exists in two complexes within cells,mTOR complex Ⅰ (mTORC1) and mTOR complex 2 (mTORC2) (Laplante and Sabatini,2012).Abundant evidence suggests that mTORC1 is the primary mTOR complex involved in regulating longevity:mutations that reduce the activity of mTORC1 have been shown to extend lifespan in yeast (Kaeberlein et al.,2005;Powers et al.,2006),nematode worms (Vellai et al.,2003;Jia et al.,2004),fruit flies (Kapahi et al.,2004),and mice (Lamming et al.,2012),as has deletion of the mTORC1 substrate ribosomal S6 kinase (Fabrizio et al.,2001,2004;Kapahi et al.,2004;Pan et al.,2007;Selman et al.,2009).Consistent with these genetic data,treatment with the mTORC1 inhibitor rapamycin has also been found to increase lifespan in yeast (Powers et al.,2006;Medvedik et al.,2007),worms (Robida-Stubbs et al.,2012),fruit flies (Bjedov et al.,2010),and mice (Harrison et al.,2009).
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Work in the Kaeberlein lab related to this topic was supported by NIH grant R01AG039390 and by the UW Nathan Shock Center of Excellence in the Basic Biology of Aging NIH grant P30AG013280.
2014-11-17（万方平台首次上网日期，不代表论文的发表时间）
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