Exploring age-related iron dysregulation: effects on longevity, body size, and behavior in C. elegans

Age-related iron accumulation is widely observed in various species and significantly impacts physiological processes. However, systematic investigation into how age-related iron dysregulation affects different life traits is still limited. This study utilizes the model organism C. elegans to examine the roles of iron regulatory genes throughout different life stages, focusing on their effects on iron homeostasis, longevity, mobility, size, and mechanosensation. Our expression analysis indicated that most iron-related genes are generally upregulated by day 15, with some peaking earlier, suggesting their crucial role in mid-life iron regulation. Lifespan assays revealed that certain mutants of non-transferrin bound iron (NTBI) uptake regulators, such as smf-1 and smf-3, are linked to extended lifespans, while zipt-17 mutants showed slightly reduced longevity. Mobility assessments indicated significant declines in speed among several mutant strains by day 7, pointing to mobility issues related to altered iron metabolism. Body size measurements varied considerably among mutant strains, with some demonstrating significant changes over time. Behavioral analyses found that most strains exhibited mechanosensory responses similar to wild-type worms at day 1; however, certain mutants displayed different rates of response reduction by day 7. FerroOrange staining confirmed increased iron accumulation with age in most mutant strains, except for zipt-16 and zipt-17, highlighting the connection between iron regulation and aging. Collectively, our current findings demonstrate that iron regulatory genes in C. elegans play diverse and critical roles in maintaining iron homeostasis, influencing lifespan, mobility, body size, and behavioral responses throughout the organism's life. These findings deepen our understanding of iron regulation's impact on health and aging in C. elegans.