title: 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. SNEV(P) (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 SNEV(P) (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 SNEV(P) (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 SNEV(P) (rp19/) (PSO) (4) and wild-type mice an increase in γ-H2AX levels, a DNA damage marker. In old SNEV(P) (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 SNEV(P) (rp19/) (PSO) (4) expression and lower levels of SNEV(P) (rp19/) (PSO) (4) , as in old SNEV(+/-) mice, result in increase in cellular senescence and acceleration of premature skin ageing.
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.|Christian Doppler Laboratory on Biotechnology of Skin Aging, Vienna, Austria.
authors.forename: Rossella
authors.initials: R
authors.lastname: Monteforte
authors.affiliation: Division of Nephrology & Dialysis, Internal Medicine III, Medical University of Vienna, Vienna, Austria.
authors.forename: Georg F
authors.initials: GF
authors.lastname: Beilhack
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.|Christian Doppler Laboratory on Biotechnology of Skin Aging, Vienna, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Grausenburger
authors.affiliation: Neuromuscular Research Department, Center of Anatomy & Cell Biology, Medical University of Vienna, Vienna, Austria.
authors.forename: Benjamin
authors.initials: B
authors.lastname: Mayerhofer
authors.affiliation: Neuromuscular Research Department, Center of Anatomy & Cell Biology, Medical University of Vienna, Vienna, Austria.
authors.forename: Reginald
authors.initials: R
authors.lastname: Bittner
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.|Evercyte GmbH, Vienna, Austria.
authors.forename: Regina
authors.initials: R
authors.lastname: Grillari-Voglauer
authors.affiliation: Institute for Cancer Research, Medical University of Vienna, Vienna, Austria.
authors.forename: Maria
authors.initials: M
authors.lastname: Sibilia
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.|Christian Doppler Laboratory on Biotechnology of Skin Aging, Vienna, Austria.
authors.forename: Hanna
authors.initials: H
authors.lastname: Dellago
authors.affiliation: Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Erwin
authors.initials: E
authors.lastname: Tschachler
authors.affiliation: Christian Doppler Laboratory on Biotechnology of Skin Aging, Vienna, Austria.|Department of Dermatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Florian
authors.initials: F
authors.lastname: Gruber
authors.affiliation: Department of Biotechnology, University of Natural Resources and Applied Life Sciences, Vienna, Austria.|Christian Doppler Laboratory on Biotechnology of Skin Aging, Vienna, Austria.|Evercyte GmbH, Vienna, Austria.
authors.forename: Johannes
authors.initials: J
authors.lastname: Grillari
mesh_terms: D019588:Aging, Premature; D000818:Animals; D016922:Cellular Senescence; D003094:Collagen / Q000378:metabolism; D017364:Collagenases / Q000378:metabolism*; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D004249:DNA Damage; D004817:Epidermis / Q000378:metabolism; D005260:Female; D005838:Genotype; D006579:Heterozygote; D006657:Histones / Q000378:metabolism; D008297:Male; D008730:Methoxsalen / Q000737:chemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D011701:PUVA Therapy / Q000379:methods*; D000072260:RNA Splicing Factors / Q000235:genetics* / Q000378:metabolism; D012867:Skin / Q000378:metabolism*; D015595:Skin Aging / Q000502:physiology*
chemical_list: D019941:Cyclin-Dependent Kinase Inhibitor p16; D006657:Histones; C518638:Prpf19 protein, mouse; D000072260:RNA Splicing Factors; D003094:Collagen; D017364:Collagenases; D008730:Methoxsalen
keywords: DNA damage response; PUVA; extracellular matrix; premature skin ageing; senescence