Caloric restriction counteracts age-dependent changes in prolyl-4-hydroxylase domain (PHD) 3 expression.
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.
Rohrbach
Susanne
S
Institute of Pathophysiology, Martin-Luther University Halle-Wittenberg, Ernst-Grube-Str. 40, 06112 Halle, Germany.
Teichert
Sabine
S
Niemann
Bernd
B
Franke
Corinna
C
Katschinski
Dörthe M
DM
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001483:Base Sequence; D031204:Caloric Restriction; D017931:DNA Primers; D008297:Male; D011393:Procollagen-Proline Dioxygenase / Q000737:chemistry / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D017931:DNA Primers; D011393:Procollagen-Proline Dioxygenase