Chlorogenic acid attenuates skin senescence and UVR-induced photoaging via the modulation of mitochondrial function

BACKGROUND: Mitochondrial function plays a critical role in skin aging. Chlorogenic acid (CGA), a botanical compound, has demonstrated regulatory effects on mitochondrial function and senescence inhibition. However, whether the anti-aging effects of CGA are attributable to its regulation of mitochondrial function remains unclear. There is a need to investigate the anti-aging effect and mechanism of CGA by modulating mitochondrial function, particularly its mode of action on mitochondrial function. METHODS: Normal human dermal fibroblasts and human epidermal keratinocytes were used to detect the regulation of collagen I production, mitochondrial functions, and anti-aging properties of CGA and confirmed by mitochondrial transplantation. The photo-aging mouse model was established by ultraviolet (UV) radiation, followed by the treatment of CGA-gel (1 mmol/kg/d) for 14 days. The skin tissues were collected and tested. RESULTS: CGA promotes collagen I (Col1) production by activating the TGF-β/Smad signaling pathway, while concurrently inhibiting cellular senescence. CGA administration significantly reduced the expression of p21, senescence-associated secretory phenotype (SASP) production, and SA-β-Gal activity in skin cells. Additionally, CGA treatment notably enhanced mitochondrial function, improving disrupted mitochondrial cristae in senescent cells and boosting the oxidative phosphorylation (OXPHOS) process. ATP levels increased by approximately 40-80% following CGA treatment. Mitochondrial transplantation further confirmed CGA's anti-aging effects are linked to mitochondrial function. CGA significantly mitigated UV-induced reduction in Col1, suppressed p21 expression and SASP production, and improved mitochondrial morphology and structure in vivo. CONCLUSION: CGA promotes Col1 production and attenuates skin cellular senescence, with these effects being directly associated with mitochondrial regulation. Thus, CGA holds promise as a potent agent for preventing cellular senescence.