Strain-Dependent Fermentation Enhances the Bioactivity of Gracilariopsis lemaneiformis Polysaccharide-Rich Fractions

Lactic acid bacterial fermentation offers a mild strategy for tailoring seaweed-derived carbohydrate fractions and strengthening their functional properties. In this study, polysaccharide-rich fractions were recovered from unfermented Gracilariopsis lemaneiformis (GP) and from biomass fermented with two marine-derived lactic acid bacteria, Lacticaseibacillus casei DS31 (GP-D) and Lactiplantibacillus plantarum HJ-S2 (GP-H). Fermentation changed the recovery of total and sulfated carbohydrates and altered monosaccharide profiles. In wild-type N2 worms, GP, GP-D, and GP-H extended mean lifespan by 8.61%, 14.70%, and 21.21%, respectively, and improved heat and oxidative stress survival (median survival +44% and +20% for GP-H, respectively), locomotion, redox homeostasis (SOD activity +19.5%, MDA content −73.4% for GP-H), and proteostasis-related phenotypes. Promoter–reporter assays, DAF-16::GFP localization, and transcriptomic profiling identified distinct treatment-associated stress-response programs. Lifespan extension also persisted in a daf-16 loss-of-function background, supporting contributions from complementary longevity networks. Collectively, strain-dependent fermentation reshaped G. lemaneiformis polysaccharide-rich fractions and enhanced their in vivo bioactivity, with GP-H producing the broadest improvement across the measured lifespan and healthspan endpoints.