Research Paper Volume 9, Issue 7 pp 1745—1769
HIF-1–dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA–binding protein MAA-1
- 1 Institut de Génomique Fonctionnelle de Lyon, Centre National de la Recherche Scientifique, Université de Lyon 1, Ecole Normale Supérieure, Lyon, France
- 2 Villum Center for Bioanalytical Sciences, Department of Biochemistry and Molecular Biology, University of Southern Denmark, Odense M, Denmark
received: April 6, 2017 ; accepted: July 22, 2017 ; published: July 27, 2017 ;https://doi.org/10.18632/aging.101267
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Copyright: Shamalnasab et al. This is an open‐access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
In yeast, the broadly conserved acyl-CoA–binding protein (ACBP) is a negative regulator of stress resistance and longevity. Here, we have turned to the nematode C. elegans as a model organism in which to determine whether ACBPs play similar roles in multicellular organisms. We systematically inactivated each of the seven C. elegans ACBP paralogs and found that one of them, maa-1 (which encodes membrane-associated ACBP 1), is indeed involved in the regulation of longevity. In fact, loss of maa-1 promotes lifespan extension and resistance to different types of stress. Through genetic and gene expression studies we have demonstrated that HIF-1, a master transcriptional regulator of adaptation to hypoxia, plays a central role in orchestrating the anti-aging response induced by MAA-1 deficiency. This response relies on the activation of molecular chaperones known to contribute to maintenance of the proteome. Our work extends to C. elegans the role of ACBP in aging, implicates HIF-1 in the increase of lifespan of maa-1–deficient worms, and sheds light on the anti-aging function of HIF-1. Given that both ACBP and HIF-1 are highly conserved, our results suggest the possible involvement of these proteins in the age-associated decline in proteostasis in mammals.