HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1

Mehrnaz Shamalnasab, Manel Dhaoui, Manjunatha Thondamal, Eva Bang Harvald, Nils J Færgeman, Hugo Aguilaniu, Paola Fabrizio

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Resumé

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.

OriginalsprogEngelsk
TidsskriftAging
Vol/bind9
Udgave nummer7
Sider (fra-til)1745-1769
Antal sider25
ISSN1945-4589
DOI
StatusUdgivet - 2017

Fingeraftryk

Diazepam Binding Inhibitor
Caenorhabditis elegans
Membranes
Molecular Chaperones
Proteome
Mammals
Maintenance
Proteins

Citer dette

Shamalnasab, Mehrnaz ; Dhaoui, Manel ; Thondamal, Manjunatha ; Harvald, Eva Bang ; Færgeman, Nils J ; Aguilaniu, Hugo ; Fabrizio, Paola. / HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1. I: Aging. 2017 ; Bind 9, Nr. 7. s. 1745-1769.
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HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1. / Shamalnasab, Mehrnaz; Dhaoui, Manel; Thondamal, Manjunatha; Harvald, Eva Bang; Færgeman, Nils J; Aguilaniu, Hugo; Fabrizio, Paola.

I: Aging, Bind 9, Nr. 7, 2017, s. 1745-1769.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - HIF-1-dependent regulation of lifespan in Caenorhabditis elegans by the acyl-CoA-binding protein MAA-1

AU - Shamalnasab, Mehrnaz

AU - Dhaoui, Manel

AU - Thondamal, Manjunatha

AU - Harvald, Eva Bang

AU - Færgeman, Nils J

AU - Aguilaniu, Hugo

AU - Fabrizio, Paola

PY - 2017

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AB - 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.

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SP - 1745

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JO - Aging

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