In Arabidopsis, POWDERY MILDEW RESISTANT 4 (PMR4) encodes the GSL5 callose synthase required for pathogen- and wound-induced callose deposition as a cell wall defense mechanism. Paradoxically, pmr4 mutants display enhanced resistance to biotrophic pathogens, which has been attributed to up-regulated salicylic acid (SA) signaling based on its dependence on Phytoalexin Deficient4 (PAD4), which controls SA accumulation, and abolishment by expressing the NahG salicylate hydroxylase. Here, we report that disruption of Arabidopsis PMR4 also causes early leaf senescence. Suppressor mutation analysis revealed that PAD4 as well as Aberrant Growth and Death2-Like Defense Response Protein1 (ALD1) and Flavin-Dependent Monoxygenase1 (FMO1), two biosynthetic genes for N-hydroxypipecolic acid (NHP), are required for early senescence of pmr4. By contrast, mutation of the SA biosynthetic gene Isochorismate Synthase1/SA Induced Deficient 2 (ICS1/SID2), which greatly reduces SA accumulation, has little effect on early senescence of pmr4. These results indicate that loss of PMR4/GSL5 callose synthase promotes early senescence through an NHP-dependent pathway. SA and NHP are two central plant immune signals involved in both local and systemic acquired resistance. The apparent differential roles of SA and NHP in disease resistance and early senescence in the pmr4 mutants provide an opportunity to dissect both shared and distinct defense pathways mediated by SA and NHP.