Sonnerachromones A–C from Sonneratia Apetala Delay Aging and Extend Lifespan in Caenorhabditis elegans Associated with Modulation of Telomere–Telomerase-Related Pathways

Fruits of Sonneratia apetala (S. apetala) are widely consumed as food and employed in traditional medicine across tropical coastal communities. Nevertheless, their pharmacological potential remains insufficiently explored. Our previous study identified a series of structurally diverse chromone derivatives from the fruits of S. apetala, termed sonnerachromones A–G (SCA–SCG), all of which extended lifespan in Caenorhabditis elegans (C. elegans). In the present study, we further evaluated their anti-aging activities and investigated their underlying molecular mechanisms. Treatment with SCA–SCG significantly enhanced heat stress resistance, reduced lipofuscin accumulation and intracellular reactive oxygen species (ROS) levels. In addition, lipid deposition was significantly decreased by SCA–SCD. Importantly, these beneficial effects were achieved without detectable adverse effects on reproductive capacity. Among the tested compounds, SCA–SCC exhibited the strongst senescence-delaying effect. Mechanistic investigations suggested that these chromone derivatives may potentially bind to telomere-associated proteins POT-1 and POT-2 and thereby influence telomere-related regulatory processes. This was associated with altered expression of telomere-related factors and increased telomerase activity, ultimately correlating with a modest attenuation of telomere shortening. Chromone derivatives from S. apetala, particularly SCA–SCC, exhibit promising anti-aging activity in C. elegans and are associated with coordinated modulation of telomere–telomerase-related processes, including changes in POT-1/POT-2-associated regulation, telomerase activity, and telomere length dynamics. These findings provide new insights into the anti-aging mechanisms of mangrove-derived chromone derivatives and support their potential as lead compounds for the development of natural anti-aging agents.