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During the centuries paper has been the most widely used writing support and therefore paper degradation is a major issue for cultural heritage conservation. The main component of paper is cellulose, one of the most abundant biomaterials on Earth. Cellulose oxidation is mainly responsible for the yellowing of the ancient samples, through the formation of optically active oxidized functional groups (chromophores). This results in severe chromatic deterioration of works of art on paper. In order to investigate the issue we applied several spectroscopic techniques (UV/Vis-IR-THz) interpreted by ab-initio theoretical computational simulations based on Density Functional theory (DFT) and Time-Dependent DFT (TDDFT) methods [1-4]. In this talk, we illustrate the experimental and theoretical methods and show their application to ancient work of art on paper. In particular, we show how to transform UV/Vis reflectance spectra of ancient samples into absorption spectra of cellulose fibers by using an improved version of the Kubelka-Munk theory suitable for strongly absorbing media. The procedure based on experimental and theoretical UV/Vis spectroscopy is particularly promising since it uses non-invasive and non-destructive measurements, which can be performed in-situ, allowing diagnostic analysis of delicate paper artifacts and the monitoring of their restoration interventions. We also present results on the state of degradation of the Leonardo Da Vinci's drawings including the famous self-portrait as well as other famous works of art on paper. [1] A Mosca Conte, O Pulci, MC Misiti, J ?ojewska, L Teodonio, C Violante and M Missori "Visual degradation in Leonardo da Vinci's iconic self-portrait: A nanoscale study" Appl. Phys. Lett.104, 224101-4 (2014). [2] M Peccianti, R Fastampa, AM Conte, O Pulci, C Violante, J ?ojewska, M Clerici, R Morandotti, M Missori "Terahertz absorption by cellulose: Application to ancient paper artifacts" Physical Review Applied 7 (6), 064019 (2017). [3] L Micheli, C Mazzuca, M Missori, L Teodonio, A Mosca Conte, O Pulci, L Arcadipane, S Dominijanni, A Palleschi, G Palleschi, S Iannuccelli, S Sotgiu, "Interdisciplinary approach to develop a disposable real time monitoring tool for the cleaning of graphic artworks. Application on "le Nozze di Psiche", Microchemical Journal 138, 369-378 (2018). [4] M Missori, D Pawcenis, J Bagniuk, A Mosca Conte, C Violante, MS Maggio, M Peccianti, O Pulci, J Lojewska, "Quantitative diagnostics of ancient paper using THz time-domain spectroscopy", Microchemical Journal 142, 54-61 (2018).