Integrated photoprotection and senescence modulation: A topical formulation counteracts cellular aging in human skin cells.

BACKGROUND

Skin aging is driven by the accumulation of senescent cells that release a pro-inflammatory mediators, which collectively disrupt tissue homeostasis. Beside ultraviolet A (UVA) and ultraviolet B (UVB) radiation, high-energy visible blue-violet (HEV) light contributes to oxidative stress, mitochondrial dysfunction and premature keratinocyte senescence. A novel photoprotective topical formulation comprising hydroxyapatite, fermented oils, baicalin and crocin was developed to counteract these effects. This study evaluated its biological effect in human skin cell models under basal conditions, oxidative stress-induced premature senescence (SIPS) and HEV exposure.

METHODS

Human dermal fibroblasts (HDFs) and immortalized keratinocytes (HaCaT) were treated with the topical formulation (0.001-1 µg/mL). Metabolic activity, long-term cell survival, apoptosis, cell cycle distribution and cell migration were evaluated using MTT, trypan blue, flow cytometry and scratch assays. Photoprotective activity of TF against HEV blue-violet light at 445 and 465 nm was evaluated by MTT assay. Stress-induced premature senescence (SIPS) was induced with H₂O₂ and assessed by senescence-associated β-galactosidase (SA-β-gal) activity. Senostatic/senolytic potential was analyzed by imaging cytometry measuring p21, IL-6 and IL-8 levels. In vivo dermal tolerability was confirmed in patch tests involving 50 volunteers, including atopic and sensitive skin subjects.

RESULTS

The topical formulation increased keratinocyte viability and promoted long-term survival of both, fibroblasts and keratinocytes, without altering cell cycle distribution. In senescent cells, it reduced SA-β-gal activity and IL-6 and IL-8 levels suggesting attenuation of senescence phenotype. Pre-application of the formulation significantly protected keratinocytes against 445 nm (11 J·cm-2) HEV irradiation. Patch testing confirmed excellent tolerability with no signs of irritation or sensitization.

CONCLUSION

The multicomponent topical formulation exerted senostatic, anti-inflammatory and HEV-photoprotective activity, combined with confirmed in vivo tolerability in sensitive skin, supporting its potential use in skin anti-aging applications.