In conclusion, exercise activation of SIRT1 can upregulate the expression of BDNF in the hippocampus through the PGC-1α/FNDC5 pathway, inhibit the expression of IL-6 and TNF-α, reduce the activity of IDO, promote the expression of 5-HT, improve the central nervous system function, and achieve anti-depression. The gene discussed is FNDC5; the disease is major depressive disorder.