Increased expression of mitochondrial transcription factor A and nuclear respiratory factor-1 in skeletal muscle from aged human subjects.

The expression of two factors involved in the nuclear-mitochondrial crosstalk, namely the mitochondrial transcription factor A (TFAM) and the nuclear respiratory factor-1 (NRF-1), was studied in human skeletal muscle biopsies of young and aged subjects. Aged subjects presented a 2.6-fold and an 11-fold increase of the levels of TFAM protein and TFAM mRNA, respectively. The increased expression of TFAM was associated to the doubling of NRF-1 DNA-binding affinity and to a 6-fold increase of NRF-1 mRNA level. The upregulation of TFAM and NRF-1, in aged skeletal muscle, appears involved in the pathway leading to the age-related increase of mitochondrial DNA content.