The fruits of Paulownia catalpifolia Gong Tong are used as a Chinese folk herbal medicine for the treatment of enteritis, tonsillitis, bronchitis, and dysentery, etc. Our previous study has identified new C-geranylated flavanones with obvious anti-proliferative effects in lung cancer A549 cells. In the present study, a new C-geranylated flavone, paucatalinone C ( 1) and five known C-geranylated flavanones ( 2–6) were isolated. In addition, a total of 34 C-geranylated flavonoids were detected by HPLC-DAD-ESI-MS/MS coupling techniques from the CH 2Cl 2 extract of P. catalpifolia. Futhermore, anti-aging effects of isolated compounds were evaluated in vitro with premature senescent 2BS cells induced by H 2O 2. Phytochemical results indicated that P. catalpifolia was a natural resource of abundant C-geranylated flavonoids. Diplacone ( 3) and paucatalinone A ( 5) were the potent anti-aging agents in the premature senescent 2BS cells induced by H 2O 2 and the C-geranyl substituent may be an important factor because of its lipophilic character.