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Caloric restriction counteracts age-dependent changes in prolyl-4-hydroxylase domain (PHD) 3 expression

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Abstract

Caloric restriction remains the most reproducible measure known to extend life span or diminish age-associated changes. Previously, we have described an elevated expression of the prolyl-4-hydroxylase domain (PHD) 3 with increasing age in mouse and human heart. PHDs modulate the cellular response towards hypoxia by regulating the stability of the α-subunit of the transcriptional activator hypoxia inducible factor (HIF). In the present study we demonstrate that elevated PHD3, but not PHD1 or PHD2, expression is not restricted to the heart but does also occur in rat skeletal muscle and liver. Elevated expression of PHD3 is counteracted by a decrease in caloric intake (40% caloric restriction applied for 6 months) in all three tissues. Age-associated changes in PHD3 expression inversely correlated with the expression of the HIF-target gene macrophage migration inhibitory factor (MIF), which has been previously described to be involved in cellular HIF-mediated anti-ageing effects. These data give insight into the molecular consequences of caloric restriction, which influences hypoxia-mediated gene expression via PHD3.

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Abbreviations

ARNT:

Aryl hydrocarbon receptor

HIF-1:

Hypoxia-inducible factor-1

MIF:

Macrophage migration inhibitory factor

PHD:

Prolyl-4-hydroxylase domain

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Acknowledgments

This work was supported by grants to D.M.K. (DFG Ka 1269/8–1) and S.R (DFG RO 2328/2–1; Deutsche Stiftung für Herzforschung F/05/05). We appreciate the technical assistance of B. Heinze.

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This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

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Authors and Affiliations

  1. Institute of Pathophysiology, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06112, Halle, Germany

    Susanne Rohrbach & Corinna Franke

  2. Department of Heart- and Circulatory Physiology, Georg-August University, Humboldtallee 23, 37073, Gottingen, Germany

    Sabine Teichert & Dörthe M. Katschinski

  3. Department of Cardiothoracic Surgery of the Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06112, Halle, Germany

    Bernd Niemann

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  1. Susanne Rohrbach
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  2. Sabine Teichert
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  3. Bernd Niemann
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  4. Corinna Franke
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  5. Dörthe M. Katschinski
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Correspondence to Dörthe M. Katschinski.

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Rohrbach, S., Teichert, S., Niemann, B. et al. Caloric restriction counteracts age-dependent changes in prolyl-4-hydroxylase domain (PHD) 3 expression. Biogerontology 9, 169–176 (2008). https://doi.org/10.1007/s10522-008-9126-x

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