Long-term exposure to third-hand smoke could accelerate biological aging via mitochondrial dysfunction: Evidence from population and animal studies

The relationship between third-hand smoke (THS) exposure and lifespan remains inadequately explored. Our study sought to clarify the effects of THS on aging and lifespan. In this pursuit, our cross-sectional analysis assessed hematological aging markers in 986 non-smokers and examined lifespan alterations using a Drosophila model. THS exposure levels were quantified through survey metrics consistent with the Global Adult Tobacco Survey. The findings revealed that THS exposure significantly accelerated biological aging, with exposed individuals exhibiting an average increase in biological age of 3.04 years compared to their unexposed counterparts (p < 0.05). Correspondingly, the Drosophila model reflected these outcomes, showing a reduction in lifespan by 16.07 days (p < 0.01). Proteomic analyses identified MRPL2 as a pivotal protein in THS-induced aging, linking its expression to mitochondrial dysfunction and oxidative stress. Further metabolomic profiling highlighted disruptions in energy metabolism pathways. Follow-up in vitro experiments confirmed the role of MRPL2 in the aging processes at the cellular level. Overall, our results indicate that THS exposure is a significant accelerant of aging, providing new perspectives on the health consequences of environmental smoke residues.