**3.2 Thymic failure during adulthood and elderly**

Atrophy implies thymic function reduction and it has been long time assumed that TL repertory was fixed during childhood and the thymus was no longer needed during adult life. However, different studies showed that adult thymus not only is functional but it can even booster its function to expedite immune reconstitution in different scenarios as chemotherapy (Mackall et al., 1995) or HIV-infected patients under highly active antiretroviral therapy (HAART) (de la Rosa and Leal, 2003).

During elderly, thymus shows even more reduced functionality. However, despite TES reduction and architectural changes, elderly thymus is able to maintain a certain degree of thymopoiesis (Jamieson et al., 1999). Thymopoietic degree is widely heterogeneous among individuals (Figure 3). In addition, thymic function in elderly people has an active role in the peripheral immune system rejuvenation (Ferrando-Martínez et al., 2009). Higher thymic function in elderly human is associated with a better preservation of the immune system. To add "insult to injury", thymic failure in healthy elderly leads to a discrete lymphopenia and naive T cell drop that eventually allows non-antigen driven homeostatic proliferation (Ferrando-Martinez et al., 2011). Homeostatic proliferation correlates with naive TL gathering age-related defects leading to irresponsiveness. Despite causality still needs to be assessed, altogether these results strongly suggest that elderly thymic function preservation or rejuvenation could be of great importance to ameliorate the age-related immune system deterioration. In fact, recent results show that thymic function, accurately measured with the sj/β-TREC ratio quantification method, in healthy elderly subjects (aged over 65) is independently associated with two-years all-cause mortality (Ferrando-Martínez et al., 2011b).Thus, elderly thymic function still has an active role in the maintenance of the immune system and this information should be taken into account to design innovative therapies capable of improve elderly quality of life through the immune system rejuvenation.
