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.
Highlights
The BimC subfamily of kinesin-1 gene belongs to a large super family of motor proteins that participate in various critical biological processes, including mitosis and intracellular transport of vesicles and organelles [1]
In studies where we modulated expression of bmk-1 in C. elegans, we found evidence indicating that bmk-1 may play an important role in lifespan determination, and that bmk-1 may be acting via hsp-16 for this effect
Bmk-1/KIF11 is an evolutionarily conserved gene, and the expression of bmk-1/KIF11 declines with mammalian tissue aging
Summary
The BimC subfamily of kinesin-1 (bmk-1) gene belongs to a large super family of motor proteins that participate in various critical biological processes, including mitosis and intracellular transport of vesicles and organelles [1]. We first generated bmk-1 over-expressing C. elegans lines that co-expressed green fluorescent protein (GFP) by a microinjection method (Supplementary Figure S1), and studied the functional impact of bmk-1 on worm longevity. Similar results were observed from RNAi inhibition in bmk-1 over-expressing worm lines (Supplementary Figure S3).
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