Immunity deteriorates as aging in human and animals, but limited knowledge about plant resistance to pathogens during aging is revealed. Aging and the resulting cell death limit the leaf life span, followed by thousands of genes that are upregulated during senescence, termed senescence-associated genes (SAGs). A lot of functional SAGs are associated with plant defense, indicating that leaf senescence and plant immunity share partial regulatory networks. Here, we found that Arabidopsis shows a trend of first reduced (mature-reduced resistance, MRR) and then enhanced (senescence-promoted resistance, SPR) resistance against Pseudomonas syringae. Two well-characterized positive regulators of age-dependent leaf senescence, ORE1 and its paralog ORS1, are required for SPR. ORE1 and ORS1 exert this regulatory effect by directly activating the transcription of immune component flavin-dependent monooxygenase1 (FMO1), resulting in the accumulation of N-hydroxypipecolic acid (NHP), the metabolic product of FMO1, in aged leaves. On the other hand, FMO1 functions as a positive regulator of leaf senescence specifically in the ORE1/ORS1-mediated senescence pathway. Moreover, NHP functions as a leaf senescence-promoting molecule and pathogen-triggered systemic senescence signal, and mutations in ORE1 and ORS1 abolish its senescence-promoting effect. Our work reveals that the ORE1/ORS1 and FMO1 pair forms a positive feedback regulatory loop, leading to hastened aging and increased pathogen defense capability in aged leaves. Since maturity increases microbial proliferation and thus, the risk for infection, the SPR may be crucial for plant survival and reproduction in its later developmental stage. Our study provides new insight into the biological role of leaf senescence.