Foxn1 regulates epidermal structure, redox balance, and age related changes

Abstract

Abstract Background Skin aging is a complex process, marked by structural decline, functional impairment, and diminished regenerative capacity. In this study, we shine a spotlight on the transcription factor Foxn1 and its pivotal role in modulating age-related changes in skin architecture and redox homeostasis. Using a murine model across three life stages (young — 20-days-old, middle-age — 1-year-old, old — 2-year-old), we compared wild-type (Foxn1 +/+ ) and Foxn1 heterozygotic knock out (Foxn1 + / - ) mice to unravel the interplay between genetic regulation and skin aging. Results Our findings reveal a striking impact of Foxn1 on skin morphology: Foxn1 +/- mice displayed thinner epidermis, thicker dermis, and disrupted keratinocyte differentiation, favoring large spinous layer of epidermal cells. Notably, the skin of Foxn1 +/+ mice was associated with increased collagen I and a shift toward repair-oriented fibers, whereas Foxn1 +/- skin maintained elevated collagen III, hinting at a preserved regenerative profile. Additionally, while p21 expression rose with age in Foxn1 +/+ mice, it remained low in Foxn1 +/- mice, suggesting an altered senescence pathway. Intriguingly, Foxn1 also emerged as a modulator of the hypoxia response, oxidative stress levels, and cellular protection, particularly in young and middle-age mice. These effects diminished with advanced age, underscoring Foxn1’s age-dependent regulatory dynamics. Conclusions Together, these results position Foxn1 as one of key regulators of skin homeostasis and reveal its potential role in skin aging processes.

The authors' abstract, as published at the source. BMC Biology, 2026 · DOI ↗