Oncotarget

Research Papers: Gerotarget (Focus on Aging):

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

Hong Qian, Xiangru Xu and Laura E. Niklason _

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Oncotarget. 2015; 6:18790-18799. https://doi.org/10.18632/oncotarget.4618

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Abstract

Hong Qian1, Xiangru Xu1,2, Laura E. Niklason1

1Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA

2Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany

Correspondence to:

Laura E. Niklason, e-mail: laura.niklason@yale.edu

Xiangru Xu, e-mail: xiangru.xu@age.mpg.de

Keywords: Geotarget, BMK-1, longevity, aging, stress response, hsp16

Received: June 20, 2015     Accepted: July 20, 2015     Published: July 31, 2015

ABSTRACT

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.


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