Ambient PM2.5 exposure causes cellular senescence via DNA damage, micronuclei formation, and cGAS activation

Abstract

Ambient PM2.5 is one of the environmental risk factors and was correlated with senescence-related diseases based on the epidemiologic investigation. However, little is known about senescence induced by PM2.5 as well as the underlying mechanisms. In this study, we demonstrated that PM2.5 exposure aggravated cellular senescence in vivo and in vitro, and disrupted micronuclei (MN) played a vital role in this process. Our results suggested that the nuclear envelope (NE) of PM2.5-induced MN was ruptured. Subsequently, cGAS was found to localize to approximately 80% of the disrupted MN but few for intact MN. Upon examination of cGAMP and SA-β-Gal, the cGAS-STING pathway was found activated and related to cellular senescence induced by PM2.5. Taken together, we reported a novel finding that PM2.5 exposure causes cellular senescence via DNA damage, MN formation, and cGAS activation. These results revealed the potential toxicity of PM2.5 and its related mechanisms in cellular senescence.

Keywords:

• PM2.5
• senescence
• cGAS
• micronuclei
• DNA damage

Ethics approval

Ethical approval was given by the Institutional Animal Care and Use Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (Reference number: SWYX-Y-2021-10) for isolation of fibroblasts. Informed consent was obtained. All mice in the study were allowed free access to water and food and all procedures were approved by the Institutional Animal Care and Use Committee of Hefei Institutes of Physical Science, Chinese Academy of Sciences (Laboratory Animal Facility License Number: SYXK-2019-010). All animals were treated humanely in accordance with the National Institutes of Health Guide for the Care and Use of Laboratory Animals.

Acknowledgments

The authors thank Prof. Sang for giving PM2.5 sample. The original NHEJ and HR Reporter was a gift from Dr. Gorbunova. A portion of the work was performed on the Steady High Magnetic Field Facilities, CAS and supported by the High Magnetic Field Laboratory of Anhui Province' should be 'The work was performed on the High Magnetic Field Laboratory of Anhui Province.

Disclosure statement

The authors report there are no competing interests to declare.

Authorship statement

Performed research: W.T., C.B., B.L., and M.J.; Conceived of study: W.T.; Analyzed data: W.T., H.W., X.S.; Designed study: X.A., W.L., and C.S.; Wrote the article: K.N. Yu, W.L., C.S.

Additional information

Funding

The work was supported by NSFC Regional Innovation and Development Joint Fund (U22A20406), the Key Program of 13th five-year plan, CASHIPS (No. KP-2017-05), and Anhui Provincial Natural Science Foundation (2108085MB41 and 2008085MC66).