Age-related thymus involution that comes with age, can lead to degenerative diseases, autoimmune diseases, tumors and opportunistic infections. Transcription factors such as forkhead box N1 (FoxN1), p63 and autoimmune regulator (AIRE) that can affect the process of age-related thymus involution and the differentiation, development and output of T cells by regulating the proliferation, development and differentiation of thymic epithelial cells(TECs). Here, we reviewed the mechanism of regulating age-related thymus involution and the research into the new treatment schemes progresses in the upstream and downstream targets of FoxN1, p63 and AIRE, miRNAs and signal pathways that affect their functions.