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.
机构:
Washington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
Ist Super Sanita, Div Nutr & Aging, I-00161 Rome, ItalyWashington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
Fontana, Luigi
Partridge, Linda
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UCL, Inst Healthy Aging & GEE, London WC1E 6BT, EnglandWashington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
Partridge, Linda
Longo, Valter D.
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Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA
Univ So Calif, Andrus Gerontol Ctr, Los Angeles, CA 90089 USAWashington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
机构:
Washington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
Ist Super Sanita, Div Nutr & Aging, I-00161 Rome, ItalyWashington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
Fontana, Luigi
Partridge, Linda
论文数: 0引用数: 0
h-index: 0
机构:
UCL, Inst Healthy Aging & GEE, London WC1E 6BT, EnglandWashington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA
Partridge, Linda
Longo, Valter D.
论文数: 0引用数: 0
h-index: 0
机构:
Univ So Calif, Dept Biol Sci, Los Angeles, CA 90089 USA
Univ So Calif, Andrus Gerontol Ctr, Los Angeles, CA 90089 USAWashington Univ, Sch Med, Div Geriatr & Nutr Sci, St Louis, MO 63110 USA