Theaflavin monomers extend Caenorhabditis elegans lifespan through insulin/IGF-1 signaling pathway

Aging is a vital contributor to numerous disorders, including diabetes, cardiovascular illnesses, and neurodegeneration. Theaflavins (TFs) exert anti-aging effects, including antioxidant, anti-inflammatory, and neuroprotective activities. Nevertheless, prior investigations mainly employed crude TF extracts, while the anti-aging active monomers and their molecular mechanisms remain unclear. This study investigated the anti-aging activities of the main monomeric compounds of TFs in Caenorhabditis elegans and explored the molecular mechanism. 100 μM TF1 and 500 μM TF2B markedly increased lifespan, enhanced resistance, and reduced lipofuscin accumulation without affecting reproductive capacity. Mechanistically, TF1 and TF2B suppressed the DAF-2-mediated insulin/IGF-1 signaling pathway. The lifespan-extending effect relied on the DAF-16/FOXO transcription factor and was independent of dietary restriction, as supported by molecular docking and mutant strain validation. Furthermore, TF1 upregulated the ubiquitin-proteasome system-related gene levels. This research revealed the molecular mechanisms for the anti-aging activity of theaflavin monomers and supports tea-based dietary strategies for healthy aging.