The role of Caenorhabditis elegans in the discovery of natural products for healthy aging

Covering: 2012 to 2023 The human population is aging. Thus, the greatest risk factor for numerous diseases, such as diabetes, cancer and neurodegenerative disorders, is increasing worldwide. Age-related diseases do not typically occur in isolation, but as a result of multi-factorial causes, which in turn require holistic approaches to identify and decipher the mode of action of potential remedies. With the advent of C. elegans as the primary model organism for aging, researchers now have a powerful in vivo tool for identifying and studying agents that effect lifespan and health span. Natural products have been focal research subjects in this respect. This review article covers key developments of the last decade (2012-2023) that have led to the discovery of natural products with healthy aging properties in C. elegans. We (i) discuss the state of knowledge on the effects of natural products on worm aging including methods, assays and involved pathways; (ii) analyze the literature on natural compounds in terms of their molecular properties and the translatability of effects on mammals; (iii) examine the literature on multi-component mixtures with special attention to the studied organisms, extraction methods and efforts regarding the characterization of their chemical composition and their bioactive components. (iv) We further propose to combine small in vivo model organisms such as C. elegans and sophisticated analytical approaches ("wormomics") to guide the way to dissect complex natural products with anti-aging properties.