Curcumin attenuates PM2.5-triggered pulmonary senescence via the mTOR/S6K1 signaling pathway

Exposure to fine particulate matter (PM2.5) triggers pulmonary inflammation and oxidative stress, which can lead to cellular senescence and a decline in lung function. Curcumin, a yellow polyphenol derived from the rhizome of Curcuma longa, is traditionally used to treat respiratory ailments. However, its potential to counteract PM2.5-induced pulmonary senescence remains underexplored. In this study, we established a murine model of PM2.5-triggered lung senescence and used BEAS-2B cells to investigate the mechanisms of curcumin. We assessed senescence markers (p16, p21, and senescence-associated β-galactosidase [SA-β-gal]) and evaluated pulmonary function. Levels of inflammatory cytokines (e.g., interleukin-1β [IL-1β], interleukin-6 [IL-6], and tumor necrosis factor-α [TNF-α]) and oxidative stress markers (e.g., malondialdehyde [MDA], superoxide dismutase [SOD], catalase [CAT], and reactive oxygen species [ROS]) were also measured. To elucidate the underlying mechanism, we examined the expression of proteins in the mammalian target of rapamycin (mTOR)/S6K1 pathway. PM2.5 exposure induced senescence, as shown by increased levels of p16, p21, and SA-β-gal, accompanied by impaired lung function. These changes coincided with elevated pro-inflammatory mediators and increased oxidative stress. PM2.5 exposure also activated the mTOR/S6K1 pathway. Curcumin treatment attenuated the senescence markers and improved lung function. It reduced oxidative stress (e.g., lowered MDA and ROS levels) and enhanced the activity of antioxidant enzymes (SOD and CAT). Curcumin also effectively inhibited mTOR/S6K1 signaling. However, its protective effects were diminished by MHY1485, an mTOR activator, which exacerbated senescence, inflammation, and oxidative stress. These findings suggest that curcumin alleviates PM2.5-induced pulmonary senescence, likely through a hormetic effect that inhibits excessive activation of the mTOR/S6K1 axis. This study highlights the translational potential of curcumin as a phytochemical intervention against PM2.5-associated respiratory damage.