This chapter summarised current knowledge on thymic senescence, a central immune tissue that suffers significant morphological changes and functional impairment during ageing. The epithelial network is in focus that provides the niche for developing thymocytes until adipose involution begins. We have discussed physiological thymic epithelial senescence in detail with respect to the signalling pathways involved in the process (Kvell et al. 2010). It has also been shown that steroid induced accelerated rate thymic epithelial senescence quite resembles physiological rate senescence (except for its speed) at the molecular level (Talaber et al. 2011). The data presented confirm that Wnt4 can efficiently rescue thymic epithelial cells from steroid-induced adipose involution at the molecular level (Talaber et al. 2011). Since physiological and steroid-induced thymic epithelial senescence are identical at the molecular level, it is anticipated that sustained Wnt4 presence in the thymic context can efficiently prolong FoxN1 expression, maintain thymic epithelial identity and prevent transdifferentiation towards adipocyte lineage. The same works identify LAP2α as a pro-ageing molecular factor promoting the trans-differentiation of thymic epithelial cells into preadipocytes via EMT. The thymus selective decrease of LAP2α activity through small molecule compounds could theoretically shift the delicate molecular balance towards the same direction as increased Wnt4 presence.