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

Rohrbach S, Teichert S, Niemann B, Franke C, Katschinski DM - Biogerontology (2008)

Bottom Line: Previously, we have described an elevated expression of the prolyl-4-hydroxylase domain (PHD) 3 with increasing age in mouse and human heart.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.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.

View Article: PubMed Central - PubMed

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

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 alpha-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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Effect of age and caloric restriction on PHD2 mRNA expression. Tissue samples (heart, liver and skeletal muscle (M. gastrocnemicus)) were obtained from young (6 months old) and old (24 months old) rats with or without a 40% caloric restriction applied for 6 months. Subsequently, RNA was extracted and PHD2 mRNA quantitated by real time PCR
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Fig2: Effect of age and caloric restriction on PHD2 mRNA expression. Tissue samples (heart, liver and skeletal muscle (M. gastrocnemicus)) were obtained from young (6 months old) and old (24 months old) rats with or without a 40% caloric restriction applied for 6 months. Subsequently, RNA was extracted and PHD2 mRNA quantitated by real time PCR

Mentions: Age-dependent changes of PHD1-3 expression were investigated in three different organs obtained from young (12 months old) and old (30 months old) rats. PHD1 and PHD2 mRNA expression did not differ significantly between the two age groups neither in heart, liver nor in skeletal muscle (Figs. 1 and 2). However, in all three different organs investigated, there was a significant increase in PHD3 mRNA expression in the tissues obtained from the old rats compared to the young animals (Fig. 3).Fig. 1


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

Rohrbach S, Teichert S, Niemann B, Franke C, Katschinski DM - Biogerontology (2008)

Effect of age and caloric restriction on PHD2 mRNA expression. Tissue samples (heart, liver and skeletal muscle (M. gastrocnemicus)) were obtained from young (6 months old) and old (24 months old) rats with or without a 40% caloric restriction applied for 6 months. Subsequently, RNA was extracted and PHD2 mRNA quantitated by real time PCR
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2367389&req=5

Fig2: Effect of age and caloric restriction on PHD2 mRNA expression. Tissue samples (heart, liver and skeletal muscle (M. gastrocnemicus)) were obtained from young (6 months old) and old (24 months old) rats with or without a 40% caloric restriction applied for 6 months. Subsequently, RNA was extracted and PHD2 mRNA quantitated by real time PCR
Mentions: Age-dependent changes of PHD1-3 expression were investigated in three different organs obtained from young (12 months old) and old (30 months old) rats. PHD1 and PHD2 mRNA expression did not differ significantly between the two age groups neither in heart, liver nor in skeletal muscle (Figs. 1 and 2). However, in all three different organs investigated, there was a significant increase in PHD3 mRNA expression in the tissues obtained from the old rats compared to the young animals (Fig. 3).Fig. 1

Bottom Line: Previously, we have described an elevated expression of the prolyl-4-hydroxylase domain (PHD) 3 with increasing age in mouse and human heart.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.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.

View Article: PubMed Central - PubMed

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

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 alpha-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.

Show MeSH
Related in: MedlinePlus