SIRT1 is a mammalian homologue of yeast longevity protein Sir2. SIRT1 deacetylates transcription factors, cofactors, and histones in an NAD+-dependent manner, and promotes cell survival, anti-oxidative function, and DNA repair. Although some studies have indicated that SIRT1 is involved in longevity, the function of SIRT1 for preventing aging and senescence is still unclear. In mouse embryonic fibroblasts (MEFs), we found that SIRT1 expression decreased by aging and IRT1 reciprocally regulated the expression level of Prl2C3, one of the prolactin-like peptides. In young MEFs, purified Prl2C3 inhibited the growth and increased the number of senescence-associated β galactosidase-positive cells with enlarged and flattened shapes. Moreover, immunostaining of human skin sections showed the expression of Prl2C3 in the basal cells of the epidermis. These results indicate that SIRT1 negatively regulates a senescence-associated protein rl2C3
