TY - JOUR
T1 - SESN-1 is a positive regulator of lifespan in Caenorhabditis elegans
AU - Yang, Ya Luen
AU - Loh, Kah Sin
AU - Liou, Bang Yu
AU - Chu, I. Hua
AU - Kuo, Cheng Ju
AU - Chen, Huan Da
AU - Chen, Chang Shi
N1 - Funding Information:
We would like to thank Drs. Lien-I Hor, Wen-Tsan Chang, and Tzu-Fun Fu for comments and helpful discussions. We thank the Caenorhabditis Genetics Center (USA), the C . elegans Gene Knockout Consortium (USA), and the National BioResource Project (Japan) for the worm strains. We acknowledge the assistance from the C . elegans core facility Taiwan funded by the National Science Council (NSC) , and feedback from the Taiwan worm research community. We also thank Miranda Loney for editing the manuscript. This work is supported by the Taiwan NSC Grants ( 98-2311-B-006-002-MY3 and 101-2311-B-006-005- ) to CSC. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript, and we have no conflict of interest to declare.
PY - 2013/3
Y1 - 2013/3
N2 - Aging is a process of gradual functional decline leading to death. Reactive oxygen species (ROS) not only contribute to oxidative stress and cell damage that lead to aging but also serve as signaling molecules. Sestrins are evolutionarily conserved in all multicellular organisms and are required for regenerating hyperoxidized forms of peroxiredoxins and ROS clearance. However, whether sestrins regulate longevity in metazoans is still unclear. Here, we demonstrated that SESN-1, the only sestrin ortholog in Caenorhabditis elegans, is a positive regulator of lifespan. sesn-1 gene mutant worms had significantly shorter lifespans compared to wild-type animals, and overexpression of sesn-1 prolonged lifespan. Moreover, sesn-1 was found to play a key role in defense against several life stressors, including heat, hydrogen peroxide and the heavy metal copper; and sesn-1 mutants expressed higher levels of ROS and showed a decline in body muscle function. Surprisingly, loss of sesn-1 did not weaken the innate immune function of the worms. Together, these results suggest that SESN-1 is required for normal lifespan and its function in muscle cells prevents muscle degeneration over a lifetime.
AB - Aging is a process of gradual functional decline leading to death. Reactive oxygen species (ROS) not only contribute to oxidative stress and cell damage that lead to aging but also serve as signaling molecules. Sestrins are evolutionarily conserved in all multicellular organisms and are required for regenerating hyperoxidized forms of peroxiredoxins and ROS clearance. However, whether sestrins regulate longevity in metazoans is still unclear. Here, we demonstrated that SESN-1, the only sestrin ortholog in Caenorhabditis elegans, is a positive regulator of lifespan. sesn-1 gene mutant worms had significantly shorter lifespans compared to wild-type animals, and overexpression of sesn-1 prolonged lifespan. Moreover, sesn-1 was found to play a key role in defense against several life stressors, including heat, hydrogen peroxide and the heavy metal copper; and sesn-1 mutants expressed higher levels of ROS and showed a decline in body muscle function. Surprisingly, loss of sesn-1 did not weaken the innate immune function of the worms. Together, these results suggest that SESN-1 is required for normal lifespan and its function in muscle cells prevents muscle degeneration over a lifetime.
UR - http://www.scopus.com/inward/record.url?scp=84874540572&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84874540572&partnerID=8YFLogxK
U2 - 10.1016/j.exger.2012.12.011
DO - 10.1016/j.exger.2012.12.011
M3 - Article
C2 - 23318476
AN - SCOPUS:84874540572
SN - 0531-5565
VL - 48
SP - 371
EP - 379
JO - Experimental Gerontology
JF - Experimental Gerontology
IS - 3
ER -