In animals and plants, immunity changes with the increase of age. The regulation of immune maturation remains largely underexplored. Heterochronic microRNAs are critical in regulating the developmental time. This work found that a conserved heterochronic microRNA (miRNA) in Arabidopsis, micro-RNA156, regulates the age-related resistance associated with the vegetative phase change, a transition from juvenile to adult during shoot development. With iR156-controlled SPL transcription factors obtaining distinct functions, the increase of disease resistance was integrated into the shoot development. Specifically, SPL10 bound and activated the key gene acting in defense, thereby enhancing the resistance in adult Arabidopsis leaves. In addition, I discovered that FLS2 (Flagellin-sensing 2), a plant immune receptor, mediated disease resistance in an age-dependent manner. The suppression of FLS2-controlled callose deposition by miR156 indicated the masked FLS2 function in juvenile phase. My work uncovered regulatory mechanisms that connect age-related resistance with vegetative phase change. By determining the developmental regulation on immunity, we anticipate removing the aging barrier from plant immunity and provide a molecular guidance for disease managements in agriculture.