NRF1 and sarcopenia: Moreover, a pronounced decline in muscle mass, muscle performance and frailty was observed in old Nrf-2 knockout (Nrf-2 KO) mice with decreased expression levels of PGC-1α, Nrf-1 and Tfam, suggesting that knockout of Nrf-2 may exacerbate skeletal muscle frailty and sarcopenia through compromising mitochondrial biogenesis [61].