Recent reports detail the pleiotropic roles sirtuins play in repressing premature aging, delaying cellular senescence, enhancing longevity, and ameliorating a wide range of aging disorders. Herein, we report our findings on the potent sirtuin activator, decapeptide-12, and compare its performance to the well documented oxyresveratrol. Treatment of human epidermal keratinocyte progenitors with 100 μM decapeptide-12 increased transcription of SIRT1 by 141±11 percent relative to control cells, whereas levels of SIRT3, SIRT6, and SIRT7 were increased by 121±13 percent, 147±8 percent and 95.4±14 percent, respectively. Decapeptide-12 upregulated sirtuin transcription to similar levels as oxyresveratrol but with reduced cytotoxicity.