Eighteen new polyesterified dihydro-β-agarofurans, celaspaculins A-R, as well as 11 known ones, were purified from the seeds of Celastrus paniculatus. The structures of new isolates were identified by extensive spectroscopic analysis and X-ray diffraction studies. The lifespan-extending activity of the dihydro-β-agarofuran-enriched fraction and 10 abundant polyesterified dihydro-β-agarofurans was evaluated on the nematode Caenorhabditis elegans model. Consequently, the dihydro-β-agarofuran-enriched fraction and compounds 5, 14, and 21 notably increased the average survival time of C. elegans by 23%, 16%, 18%, and 17%, respectively, compared with the blank control group (p < 0.0001).