Aire (autoimmune regulator) has a key role in the establishment of tolerance to autoantigens. Aire−/− mice present decreased thymic expression of AChR, significantly lower frequencies of regulatory T (Treg) cells, and higher expression of Th17 markers, compared to controls. We therefore predicted that Aire−/− mice would be more susceptible to induction of experimental autoimmune myasthenia gravis (EAMG). However, when EAMG was induced in young mice, Aire−/− mice presented a milder disease that wild‐type (WT) controls. In contrast, when EAMG was induced in older mice, Aire−/− mice were more severely affected than WT mice. The relative resistance to EAMG in young Aire−/− mice correlated with increased numbers of Treg cells in their spleens compared to young controls. A similar age‐related susceptibility was also observed when EAE was induced in Aire−/− mice, suggesting an age‐related link among Aire, disease susceptibility, and peripheral Treg cells that may be a general feature of autoimmunity.