Bmk-1 regulates lifespan in Caenorhabditis elegans by activating hsp-16

被引:2
作者
Qian, Hong [1 ]
Xu, Xiangru [1 ,2 ]
Niklason, Laura E. [1 ]
机构
[1] Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06520 USA
[2] Max Planck Inst Biol Ageing, D-50931 Cologne, Germany
关键词
Geotarget; BMK-1; longevity; aging; stress response; hsp16; HEAT-SHOCK FACTOR; C-ELEGANS; KINESIN SUPERFAMILY; PROTEIN; DAF-16; EXPRESSION; LONGEVITY; PATHWAY; STRESS; MOTORS;
D O I
10.18632/oncotarget.4618
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
The genetics of aging is typically concerned with lifespan determination that is associated with alterations in expression levels or mutations of particular genes. Previous reports in C. elegans have shown that the bmk-1 gene has important functions in chromosome segregation, and this has been confirmed with its mammalian homolog, KIF11. However, this gene has never been implicated in aging or lifespan regulation. Here we show that the bmk-1 gene is an important lifespan regulator in worms. We show that reducing bmk-1 expression using RNAi shortens worm lifespan by 32%, while over-expression of bmk-1 extends worm lifespan by 25%, and enhances heat-shock stress resistance. Moreover, bmk-1 over-expression increases the level of hsp-16 and decreases ced-3 in C. elegans. Genetic epistasis analysis reveals that hsp-16 is essential for the lifespan extension by bmk-1. These findings suggest that bmk-1 may act through enhanced hsp-16 function to protect cells from stress and inhibit the apoptosis pathway, thereby conferring worm longevity. Though it remains unclear whether this is a distinct function from chromosomal segregation, bmk-1 is a potential new target for extension of lifespan and enhancement of healthspan.
引用
收藏
页码:18790 / 18799
页数:10
相关论文
共 41 条
[21]   EGF-Induced Centrosome Separation Promotes Mitotic Progression and Cell Survival [J].
Mardin, Balca R. ;
Isokane, Mayumi ;
Cosenza, Marco R. ;
Kraemer, Alwin ;
Ellenberg, Jan ;
Fry, Andrew M. ;
Schiebel, Elmar .
DEVELOPMENTAL CELL, 2013, 25 (03) :229-240
[22]   Transcriptional outputs of the Caenorhabditis elegans forkhead protein DAF-16 [J].
McElwee, J ;
Bubb, K ;
Thomas, JH .
AGING CELL, 2003, 2 (02) :111-121
[23]   Analysis of the kinesin superfamily: insights into structure and function [J].
Miki, H ;
Okada, Y ;
Hirokawa, N .
TRENDS IN CELL BIOLOGY, 2005, 15 (09) :467-476
[24]   Regulation of longevity in Caenorhabditis elegans by heat shock factor and molecular chaperones [J].
Morley, JF ;
Morimoto, RI .
MOLECULAR BIOLOGY OF THE CELL, 2004, 15 (02) :657-664
[25]   Genes that act downstream of DAF-16 to influence the lifespan of Caenorhabditis elegans [J].
Murphy, CT ;
McCarroll, SA ;
Bargmann, CI ;
Fraser, A ;
Kamath, RS ;
Ahringer, J ;
Li, H ;
Kenyon, C .
NATURE, 2003, 424 (6946) :277-284
[26]  
Qian H, 2015, AGING-US, V7, P1
[27]   Reduction in DNA methyltransferases and alteration of DNA methylation pattern associate with mouse skin ageing [J].
Qian, Hong ;
Xu, Xiangru .
EXPERIMENTAL DERMATOLOGY, 2014, 23 (05) :357-359
[28]   Chromosome passenger complexes control anaphase duration and spindle elongation via a kinesin-5 brake [J].
Rozelle, Daniel K. ;
Hansen, Scott D. ;
Kaplan, Kenneth B. .
JOURNAL OF CELL BIOLOGY, 2011, 193 (02) :285-294
[29]   Targeting the Kinesin Spindle Protein: Basic Principles and Clinical Implications [J].
Sarli, Vasiliki ;
Giannis, Athanassios .
CLINICAL CANCER RESEARCH, 2008, 14 (23) :7583-7587
[30]   Kinesin-5 acts as a brake in anaphase spindle elongation [J].
Saunders, Adam M. ;
Powers, James ;
Strome, Susan ;
Saxton, William M. .
CURRENT BIOLOGY, 2007, 17 (12) :R453-R454