These facts suggest that HDAC4/Gadd45α axis plays an important role in hindlimb unloading-induced muscle atrophy in aged skeletal muscle; thus, HDAC4/Gadd45α axis may be a key pathway for developing potential therapeutic countermeasures in aged muscles before muscle disuse and in identifying target molecules to protect against disuse skeletal muscle atrophy. Here, HDAC4 is linked to muscle atrophy.