SNEVPrp19/PSO4 deficiency increases PUVA‐induced senescence in mouse skin

Senescent cells accumulate during ageing in various tissues and contribute to organismal ageing. However, factors that are involved in the induction of senescence in vivo are still not well understood. SNEV^Prp19/PSO4 is a multifaceted protein, known to be involved in DNA damage repair and senescence, albeit only in vitro. In this study, we used heterozygous SNEV^+/? mice (SNEV‐knockout results in early embryonic lethality) and wild‐type littermate controls as a model to elucidate the role of SNEV^Prp19/PSO4 in DNA damage repair and senescence in vivo. We performed PUVA treatment as model system for potently inducing cellular senescence, consisting of 8‐methoxypsoralen in combination with UVA on mouse skin to induce DNA damage and premature skin ageing. We show that SNEV^Prp19/PSO4 expression decreases during organismal ageing, while p16, a marker of ageing in vivo, increases. In response to PUVA treatment, we observed in the skin of both SNEV^Prp19/PSO4 and wild‐type mice an increase in γ‐H2AX levels, a DNA damage marker. In old SNEV^Prp19/PSO4 mice, this increase is accompanied by reduced epidermis thickening and increase in p16 and collagenase levels. Thus, the DNA damage response occurring in the mouse skin upon PUVA treatment is dependent on SNEV^Prp19/PSO4 expression and lower levels of SNEV^Prp19/PSO4, as in old SNEV^+/? mice, result in increase in cellular senescence and acceleration of premature skin ageing.