Turnera diffusa polysaccharides promote healthy aging through conserved stress response regulation and metabolic remodeling across multiple aging models.

Aging is a progressive decline in physiological functions and the capacity to maintain homeostasis, representing a major risk factor for numerous chronic diseases. Geroprotectors, defined as natural or synthetic compounds capable of improving healthspan and delaying age-associated functional decline, have attracted increasing attention in aging research. However, clinically validated interventions for promoting healthy aging remain unavailable. Plant-derived polysaccharides, owing to their excellent safety profiles and diverse biological activities, have emerged as promising candidates for geroprotection. Turnera diffusa Willd. Ex Schult. (T. diffusa) has been reported to exhibit neuroprotective and reproductive system modulating properties; however, the geroprotective potential of its polysaccharides remains unexplored. In the present study, T. diffusa polysaccharides (TDP) were found to significantly extend lifespan and alleviate multiple age-associated physiological declines in both C. elegans and D. melanogaster models. Mechanistic investigations revealed that TDP enhanced the activation of conserved DAF-16/FOXO and HSF-1-mediated stress response pathways, thereby promoting antioxidant defense and maintaining proteostasis. Furthermore, 1H-NMR-based metabolomic analysis demonstrated that TDP partially restored age-related metabolic disturbances, particularly those associated with amino acid, energy, and lipid metabolism. These findings provide novel insights into the geroprotective potential of TDP and support its further investigation as a potential geroprotective candidate.