SNEV(Prp19/PSO4) deficiency increases PUVA-induced senescence in mouse skin.

Abstract

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. SNEVP rp19/ PSO 4 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 SNEVP rp19/ PSO 4 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 SNEVP rp19/ PSO 4 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 SNEVP rp19/ PSO 4 and wild‐type mice an increase in γ‐H2AX levels, a DNA damage marker. In old SNEVP rp19/ PSO 4 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 SNEVP rp19/ PSO 4 expression and lower levels of SNEVP rp19/ PSO 4, as in old SNEV +/− mice, result in increase in cellular senescence and acceleration of premature skin ageing.