A homogalacturonan polysaccharide from Anemarrhena asphodeloides promotes longevity in Caenorhabditis elegans with involvement of DAF-16/FOXO.

Abstract

Aging is a biologically complex process, and the search for safe and effective natural anti-aging compounds has attracted increasing attention. Anemarrhena asphodeloides Bunge is a traditional Chinese medicinal herb rich in bioactive polysaccharides, but the anti-aging activity and underlying mechanisms of its pectin polysaccharides remain unclear. In this study, a homogeneous polysaccharide, designated AAP50-2, was isolated and purified from A. asphodeloides. Structural characterization indicated that AAP50-2 was a homogalacturonan (HG)-type pectin polysaccharide, characterized by a backbone of α-1,4-linked D-GalpA residues. In wild-type N2 Caenorhabditis elegans, AAP50-2 treatment at 50, 100, and 200 μg/mL increased the maximum lifespan from 16 days in the control group to 18, 20, and 25 days, corresponding to increases of 12.5%, 25%, and 56.3%, respectively. AAP50-2 also improved healthspan-related indicators, including enhanced locomotor activity and pharyngeal pumping, reduced lipofuscin accumulation by 44-65%, and improved resistance to heat and juglone-induced oxidative stress, with maximum survival increases of 1.75-fold and 2.2-fold, respectively. Mechanistically, AAP50-2 was associated with IIS/DAF-16-related signaling, as indicated by reduced daf-2 and age-1 mRNA levels, enhanced DAF-16 nuclear translocation, and increased expression of DAF-16-associated stress-response genes, including sod-3, ctl-1, and hsp-16.2. Mutant lifespan assays further supported the involvement of daf-2 and daf-16 in the effects of AAP50-2. These findings suggested that AAP50-2 is a promising HG-type pectin polysaccharide from A. asphodeloides with potential as a natural anti-aging functional ingredient.