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1Department of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden; 2Steno Diabetes Center, Gentofte, Denmark; and 3Department of Medicine, Helsinki University, Helsinki, Finland
Submitted 26 February 2008 ; accepted in final form 21 April 2008
Maximal oxygen uptake (
O2max) and the amount of type 1 fibers are interrelated, but the underlying unifying molecular mechanisms are poorly understood. To explore these mechanisms, we related gene expression profiles in skeletal muscle biopsies of 43 age-matched men from published datasets with
O2max and the amount of type 1 fibers and replicated some of the findings in muscle biopsies from 154 young and elderly individuals using real-time PCR. We identified 66 probe sets (genes or expressed sequence tags) positively and 83 probe sets inversely correlated with
O2max and 171 probe sets positively and 217 probe sets inversely correlated with percentage of type 1 fibers in human skeletal muscle. Genes involved in oxidative phosphorylation (OXPHOS) showed high expression in individuals with high
O2max, whereas the opposite was not the case in individuals with low
O2max. Instead, genes such as AHNAK and BCL6 were associated with low
O2max. Also, expression of the OXPHOS genes NDUFB5 and ATP5C1 increased with exercise training and decreased with aging. In contrast, expression of AHNAK in skeletal muscle decreased with exercise training and increased with aging. Eleven genes (NDUFB4, COX5A, UQCRB, ATP5C1, ATP5G3, ETHE1, FABP3, ISCA1, MYST4, C9orf3, and PKIA) were positively correlated with both
O2max and the percentage of type 1 fibers.
O2max closely reflects expression of OXPHOS genes, particularly that of NDUFB5 and ATP5C1, in skeletal muscle, suggesting good muscle fitness. In contrast, a high expression of AHNAK was associated with a low
O2max and poor muscle fitness.
aging; AHNAK; oxidative phosphorylation; exercise
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