To clarify the function of p21 or p16 in modulating aging phenotypes in the background of WS, we crossed the WS mice with p21–/– or p16–/– mice and obtained triple knockout mice mTer–/–Wrn–/–p21–/– (p21-TKO) or mTer–/–Wrn–/–p16–/– (p16-TKO). Here, CDKN2A is linked to Werner syndrome.