GenIV fast reactors (FR) development would increase the sustainable use of the uranium resources and mitigate long term impact of nuclear waste generated by nuclear power production. These reactors, however, require the design and development of nuclear fuel (NF) withstanding the most extreme irradiation and temperature conditions. High plutonium content MOX fuels are envisaged (for example 30% Pu-enriched in MYRRHA). A deep and complete understanding of the behaviour of such MOX fuels for FR is hence one of the key aspects towards the licensing process of the reactors. The high alpha-decay activity from the plutonium content in MOX fuel leads to the formation of large amount of defects which will induce measurable effects even before irradiation in the reactor. The fluorite structure common to all actinide dioxides is known as being a crystal configuration resistant to radiation damage. Nevertheless, high alpha-dose can affect the stability of materials envisaged as fuels. Furthermore, when the alpha-particle comes to rest it becomes a helium atom that can alter the microstructure of the material, e.g. by forming microscopic bubbles. At the downstream of the fuel cycle, the radiotoxicity of the irradiated fuel will be mainly due to the minor actinides (MA) accumulation, including plutonium. Over the medium-term period alpha-decay will also significantly contribute to the heat load, e.g. during extended storage in the case of LWR. In the present work we report on new experimental observations obtained by TEM, LAF, XRD, RAMAN and DSC of the self-irradiation alpha-damage effect on Uranium-Plutonium MOX fuel samples with a variety of Plutonium content and of different isotopic composition, different storage time and hence different damage levels. The results for samples with higher alpha-dose can be used to forecast the ageing consequences affecting the behaviour of spent fuel over several centuries or millennia of storage/disposal.