Our previous finding demonstrated that chronic corticosterone (CORT) may be involved in mediating the pathophysiology of premature aging in rats.Frequent jet lag increases the risk for many diseases,includingobesity and type 2 diabetes,and is associated with the aging processes.However,the effect of jet lag on CORT-induced depression and its association with aging phenotypes remain unclear.In this study,the rats were exposed to both CORT and jet lag treatment,and the differences were analyzed and compared to rats with single CORT treatment.Our results showed that jet lag treatment aggravated CORT-induced depression-like behavior evidenced by sucrose intake test,forced swimming test,and open field test.Additionally,this treatment aggravated the shortening of telomeres,which possibly resulted in decreased telomerase activity,and downregulated the expression of telomere-binding factor 2 (TRF2) and telomerase reverse transcriptase compared to that in CORT rats,as revealed by quantitative real-time-polymerase chain reaction and weste blot analysis,respectively.The shortening of telomeres may have been caused by increased oxidative stress,which was associated with the inhibition of sirtuin 3.Exposure to jet lag also aggravated the degeneration of mitochondrial functions,as shown by the decreases in the mRNA expression of COX1,ND1,and Tfam.Our findings provide physiological evidence that jet lag exposure may worsen stress-induced depression and age-related abnormalities.