Age-dependent IGF-1 regulation of gene transcription of Ca2+ channels in skeletal muscle.

In the present work, we investigated whether IGF-1 regulates the transcription of the genes encoding the L-type Ca2+ channel (DHPR) channel and RyR1 in young adult and senescent mice. To this end, a transgenic mouse model overexpressing IGF-1 exclusively in skeletal muscle (S1S2) was studied at different ages and the results were compared with wild type age-matched mice (FVB). We found that ribosomal RNA expression did not change significantly either with age or IGF-1 according to ribonuclease protection and nuclear run-on transcription assays. Transgenic overexpression of IGF-1 resulted in marked increases in skeletal muscle DHPR alpha(1S) and RyR1 mRNA in young and old mice and in enhanced DHPR alpha(1S) nuclear transcription in skeletal muscles from young mice when normalized to 28S ribosomal RNA. These results support the concept that IGF-1 regulates the expression of DHPR by modulating DHPR alpha(1S) nuclear transcription.