PPARGC1A and osteosarcoma: However, the levels regulating mitochondrial biogenesis reportedly increase in cellular senescence and aging; upregulation of TFAM and NRF1 in the age-related increase in mtDNA content in human lung fibroblasts, osteosarcoma 143B TK and skeletal muscle [29, 41], and increased expression of NRF2α, PGC-1α, PGC-1β, and TFAM in ras-induced senescence [42].