Thus, since physical and biochemical barriers have been exhaustively studied in this pathosystem without any clear pattern for the observed ontogenic resistance, other aspects to be considered are genes that are differentially expressed between young and old leaves. Furthermore, analyses to unveil the constitutive or pathogen-induced nature of the ontogenic resistance are needed. Today, the rapidly evolving sequencing techniques based on total RNA sequencing, have decreased costs of analysis and increased the precision of results, allowing the researcher to maximise data outputs minimising their laboratory work and manipulation bias. RNA-seq uses next generation sequencing technology to sequence and quantify transcripts. With the technical progress of this rapidly evolving technology, some Dimesna studies have focused the research at the transcriptome level to find fungal effectors and mechanisms involved in plant defences against microorganisms like chemical defences and structural defences. Thus, today, NGS appears to be the most promising methodology to study plant pathogen interactions in non-model species like Malus x domestica. Moreover, the genome sequence of Malus x domestica ��Golden Delicious’has been recently published. The aim of this work was to identify and characterise genes that are significantly differentially expressed during the shift from the susceptibility of young leaves to the resistance of old fully expanded leaves of the apple plant. Moreover, the constitutive or induced mechanism behind ontogenic resistance were studied by comparing inoculated and uninoculated leaves in the early phase of fungal colonisation at 72 and 96 hours post-inoculation. The data presented in this work will add more knowledge to the Venturia-Malus pathosystem and provide new insight for future researches on ontogenic resistance in apple. The role of MTs in response to biotic stress is not fully understood; however, some suggestions were made: the upregulation of MT3 may inhibit fungal growth through metal ion sequestration, leading to an unsuitable habitat for fungal growth, or by decreasing the fungal enzymatic activity ; thus, in both situations, an inhibition of fungal growth may be expected. However, since ontogenic resistance in old senescing leaves is no longer functional, further studies on MTs at the senescence stadium must be performed. Tocopherol, part of the vitamin E group, has been postulated to have antioxidant qualities to maintain the chemical and physical properties of the epicuticular waxes. This substance was found to improve fruit quality by decreasing disease incidence. In the work of Bringe et al., an increase of tocopherol between leaf one and leaf seven has been observed. In our work, we found a constant Sibutramine HCl down-regulation of genes involved in the biosynthesis of tocopherol in old leaves at both time points. This result does not contrast with the findings of Bringe et al. if tocopherol, as suggested previously, accumulates in old leaves. However, at the onset of autumn, leaves lose their ontogenic resistance ; therefore, it is unlikely that tocopherol plays an important function in this resistance mechanism. Phenols and flavonoids have been extensively studied in the past five decades in apple tissues apparently without any conclusive answer to the observed age-related resistance. In the present work, flavonoids and phenols precursor genes were downregulated or not differentially expressed in old leaves of the conditions tested. Nitrate, ammonium, sulphate and phosphate transporter genes were up-regulated in both uninoculated and inoculated old leaves in most of the tested conditions.