Multi-Ingredient Supplement Supports Mitochondrial Health through Interleukin-15 Signaling in Older Adult Human Dermal Fibroblasts

The macroscopic and microscopic deterioration of human skin with age is, in part, attributed to a functional decline in mitochondrial health. We previously demonstrated that exercise attenuated age-associated changes within the skin through enhanced mitochondrial health via IL-15 signaling, an exercise-induced cytokine whose presence increases in circulation following physical activity. The purpose of this investigation was to determine if these mitochondrial-enhancing effects could be mimicked with the provision of a novel multi-ingredient supplement (MIS). Cultured human fibroblasts isolated from older, sedentary women were treated with control media (CON) or CON supplemented with the following active ingredients to create the MIS: coenzyme Q10, alpha lipoic acid, resveratrol, curcumin, zinc, lutein, astaxanthin, copper, biotin, and vitamins C, D, and E. Outcomes were determined following 24 or 72 h of treatment. MIS provision to dermal fibroblasts significantly increased the mRNA abundance of mitochondrial biogenesis activators and downstream IL-15 signaling pathways, and proteins for oxidative phosphorylation subunits and antioxidant defenses. These findings were co-temporal with lower cellular senescence and cytotoxicity following MIS treatment. In summary, MIS supplementation led to exercise-mimetic effects on human dermal fibroblasts and their mitochondria by reproducing the molecular and biochemical effects downstream of IL-15 activation.