Camille K. Stevenson, Jiang Wang, Chunying Du
), and sirtuin reduction (SIRT1 and SIRT7). Mechanistically, chronic PFOS downregulated autophagy complexes (ULK1-FIP200-ATG13 and ATG14L-Beclin1-Vps34) and reduced LC3B-I/II conversion, indicating impaired autophagosome formation and blocked flux. Pharmacological restoration of autophagy in PFOS-treated AML12 cells ameliorated intracellular lipid droplets, canalicular disruption, oxidative stress and aging pigment buildup, suggesting PFOS as a silent driver of irreversible liver aging at least through autophagy suppression. Finally, transcriptomics of PFOS-exposed human liver spheroids recapitulated aging and cholestasis, underscoring translational relevance. These findings redefine the occupational toxicological profile of PFOS, supporting the inclusion of congestion, pigment, and aging biomarkers in occupational PFAS assessments.