Abstract / Summary
Introduction: Photoaging and chronological age-related changes in cellular functioning such as telomere attrition can lead to accumulation of senescent skin cells, a key driver of age-related decline in skin integrity and function. Activation of sirtuins (SIRTs), master epigenetic regulators of cellular functioning and homeostasis in skin, may be a promising approach to protect skin cells from the effects of photoaging and cellular hallmarks of skin aging. Methods: In a series of in vitro studies, we evaluated the potential for a SIRT6 activator, a proprietary Hydrolyzed Yeast Protein Extract (HYPE), to modulate the response of normal human epidermal keratinocytes (NHEK) to UVB radiation, the rate of telomere attrition in dermal fibroblasts, and melanin content in melanocytes in a 3D skin model. Results: Treatment with HYPE increased SIRT6 protein expression in NHEK and SIRT6 gene expression in dermal fibroblasts, attenuated NF-κB-mediated inflammation in keratinocytes following UVB exposure, protected keratinocytes from DNA damage following UVB irradiation, decreased the rate of telomere attrition in aged dermal fibroblasts, and reduced melanin content in melanocytes in a 3D skin model. Conclusion: The potential for the SIRT6 activator HYPE to address multiple hallmarks of skin aging, and its activity in all 3 types of skin cells, makes it a potential agent to incorporate into skincare formulations designed to reverse visible aging.