The TFEB orthologue HLH-30 regulates autophagy and modulates longevity in Caenorhabditis elegans

被引：383

作者：

Lapierre, Louis R. ^{[1
]}

De Magalhaes Filho, C. Daniel ^{[2
]}

McQuary, Philip R. ^{[1
,3
]}

Chu, Chu-Chiao ^{[1
]}

Visvikis, Orane ^{[4
]}

Chang, Jessica T. ^{[1
]}

Gelino, Sara ^{[1
,3
]}

Ong, Binnan ^{[1
]}

Davis, Andrew E. ^{[1
]}

Irazoqui, Javier E. ^{[4
]}

Dillin, Andrew ^{[2
]}

Hansen, Malene ^{[1
]}

机构：

[1] Sanford Burnham Med Res Inst, Aging & Stem Cell Res Ctr, Program Dev & Aging, La Jolla, CA USA

[2] Salk Inst Biol Studies, Howard Hughes Med Inst, Glenn Ctr Aging Res, La Jolla, CA 92037 USA

[3] Sanford Burnham Med Res Inst, Grad Sch Biomed Sci, La Jolla, CA USA

[4] Harvard Univ, Sch Med, Dept Pediat, Massachusetts Gen Hosp, Boston, MA 02115 USA

来源：

NATURE COMMUNICATIONS | 2013年 / 4卷

关键词：

LIFE-SPAN EXTENSION; DIETARY RESTRICTION; LIPID-METABOLISM; GENES; GENETICS; LYSOSOME; CONSUMPTION; INHIBITION; PHA-4/FOXA; PATHWAYS;

D O I：

10.1038/ncomms3267

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Autophagy is a cellular recycling process that has an important anti-aging role, but the underlying molecular mechanism is not well understood. The mammalian transcription factor EB (TFEB) was recently shown to regulate multiple genes in the autophagy process. Here we show that the predicted TFEB orthologue HLH-30 regulates autophagy in Caenorhabditis elegans and, in addition, has a key role in lifespan determination. We demonstrate that hlh-30 is essential for the extended lifespan of Caenorhabditis elegans in six mechanistically distinct longevity models, and overexpression of HLH-30 extends lifespan. Nuclear localization of HLH-30 is increased in all six Caenorhabditis elegans models and, notably, nuclear TFEB levels are augmented in the livers of mice subjected to dietary restriction, a known longevity-extending regimen. Collectively, our results demonstrate a conserved role for HLH-30 and TFEB in autophagy, and possibly longevity, and identify HLH-30 as a uniquely important transcription factor for lifespan modulation in Caenorhabditis elegans.

引用

页数：8