Aspartame at 100 μM concentrations activated autophagy genes (bec-1, unc-51, lgg-1, lgg-2, atg-5) in C. elegans worms, extending lifespan while enhancing resistance to Pseudomonas aeruginosa infections. Among six artificial sweeteners tested, only aspartame demonstrated these protective effects, reducing bacterial burden in the intestine and improving antioxidant capacity through the evolutionarily conserved autophagy pathway. This finding challenges prevailing narratives about aspartame's health effects by revealing a potential longevity mechanism. Autophagy, the cellular 'housekeeping' process that removes damaged components, declines with age and represents a key hallmark of aging. The ability of aspartame to upregulate this pathway suggests possible benefits for cellular maintenance and stress resistance. However, the 100 μM concentration used exceeds typical human dietary exposure levels, and C. elegans findings don't always translate to mammals. The research contradicts widespread concerns about aspartame safety, though the worm model limits direct human applicability. This represents an intriguing mechanistic discovery that warrants investigation in mammalian models, particularly given autophagy's central role in aging and age-related diseases.