Age-dependent changes of p57 Kip2 and p21 Cip1/Waf1 expression in skeletal muscle and lung of mice

Abstract

p57 Kip2 and p21 Cip1/Waf1 are members of cyclin-dependent kinase (Cdk) inhibitors which play critical roles in the terminal differentiation of skeletal muscle and lung. We investigated mRNA levels of p57 Kip2 and p21 Cip1/Waf1 in skeletal muscle and lung of mice during maturation and aging using Northern hybridization. The mRNA levels of p57 Kip2 and p21 Cip1/Waf1 decreased in skeletal muscle and lung of mice during maturation and aging except that the level of p21 Cip1/Waf1 mRNA in skeletal muscle of mice showed an increase only during maturation. The decrease of the p57 Kip2 mRNA level involved neither a change of DNA methylation at the promoter region nor an alteration of the imprinting status in aged mice. The decreases of p57 Kip2 and p21 Cip1/Waf1 mRNA levels during aging suggest that the process of tissue-specific terminal differentiation may be gradually downregulated with senescence in tissues where p57 Kip2 and p21 Cip1/Waf1 play key roles in differentiation. The downregulation of p57 Kip2 and p21 Cip1/Waf1 during aging is contrary to the upregulation of Cdk inhibitors during cellular replicative senescence, indicating that aging in an organismal level is mediated by mechanisms different from replicative senescence of cultured cells.