Objective To investigate the role of SIRTI in Ginkgo Biloba Extract 50 (GBE50) delaying telomere shortening in the hippocampus of natural aging rats Method Thirty Sprague-Dawley (SD) rats (male, 21 months, 700-1050g) were randomly divided into GBE50 treated group, Ginkgo biloba extract 761(EGB761) treated group and model group (n=10 each). Eight SD rats (male,1 months, 100-110g,) were control group. GBE50 group and EGB761 group were respectively administered intragastrically with GBE50 (100mg/kg/day) and EGB761 (100mg/kg/day) dissolved in 1% Carboxymethyl-cellulose Sodium (CMC-Na) for 60 days. The control group and the model group were treated intragastrically with 1% CMC-Na for 60 days. Rats in each group were anaesthetised with 25℅ urethane(3ml kg-1, both i.p.) and sacrificed after 60 days, and hippocampus were taken out for analysis of RNA, DNA and protein. Telomere length and SIRTl mRNA in the hippocampus were determined by fluorescent quantitative real-time polymerase chain reaction (RT-PCR), Western blot was used to analyze the levels of Sirtl, p53 and p21 respectively. Expressions of p53 and p21 in hippocampal region CA1 were quantified by immunohistochemistry . Results (1) Significant difference in telomere length was observed between model group and control group (P<0.05). The length of telomere was significantly longer in GBE50 group compared to model group (P<0.05). GBE50 could delay telomere shortening(24.2%). (2) SIRTl mRNA and protein levels were significantly lower in model group relative to control group (P<0.05). GBE50 could increase SIRTl mRNA and protein level compared to model group (P<0.05). (3) The protein level of p21 was increased in model group relative to control group (P<0.05). GBE50 could significantly decrease p21 compared to model samples (P<0.05). However, any difference wasn’t detected in the expression of p53 among model group, control group and GBE50 group (P>0.05). (4) GBE50 could inhibit protein expressions of p21 in hippocampal region CA1 ( P< 0.05). Conclusion GBE50 might delay telomere shortening in the hippocampus of natural aging rats through up-regulated the SIRTl expression, and the expression of p21 were down-regulated.