title: Bmk-1 regulates lifespan in Caenorhabditis elegans by activating hsp-16.
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.
authors: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Hong
authors: H
authors: Qian
authors: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.|Max Planck Institute for Biology of Ageing, 50931, Cologne, Germany.
authors: Xiangru
authors: X
authors: Xu
authors: Department of Anesthesiology, Yale University School of Medicine, New Haven, CT 06520, USA.
authors: Laura E
authors: LE
authors: Niklason
mesh_terms: D000375:Aging / Q000235:genetics*; D000818:Animals; D017173:Caenorhabditis elegans; D029742:Caenorhabditis elegans Proteins / Q000378:metabolism*; D006360:Heat-Shock Proteins / Q000378:metabolism*; D018869:Heat-Shock Response / Q000235:genetics; D006801:Humans; D016547:Kinesins / Q000378:metabolism*; D008136:Longevity / Q000235:genetics*; D051379:Mice; D015398:Signal Transduction
chemical_list: D029742:Caenorhabditis elegans Proteins; D006360:Heat-Shock Proteins; C108431:hsp-16.2 protein, C elegans; C000605617:BMK-1 protein, C elegans; D016547:Kinesins
keywords: BMK-1; Geotarget; aging; hsp16; longevity; stress response