Influence of aging in the modulation of epigenetic biomarkers of carcinogenesis after exposure to air pollution

Exp Gerontol. 2018 Sep:110:125-132. doi: 10.1016/j.exger.2018.05.018. Epub 2018 May 31.

Abstract

Background: Classified as carcinogenic to humans by the IARC in 2013, fine air particulate matter (PM2.5) can be inhaled and retained into the lung or reach the systemic circulation. This can cause or exacerbate numerous pathologies to which the elderly are often more sensitive.

Methods: In order to estimate the influence of age on the development of early cellular epigenetic alterations involved in carcinogenesis, peripheral blood mononuclear cells sampled from 90 patients from three age classes (25-30, 50-55 and 75-80 years old) were ex vivo exposed to urban PM2.5.

Results: Particles exposure led to variations in telomerase activity and telomeres length in all age groups without any influence of age. Conversely, P16INK4A gene expression increased significantly with age after exposure to PM2.5. Age could enhance MGMT gene expression after exposure to particles, by decreasing the level of promoter methylation in the oldest people.

Conclusion: Hence, our results demonstrated several tendencies in cells modification depending on age, even if all epigenetic assays were carried out after a limited exposure time allowing only one or two cell cycles. Since lung cancer symptoms appear only at an advanced stage, our results underline the needs for further investigation on the studied biomarkers for early diagnosis of carcinogenesis to improve survival.

Keywords: Aging; Biomarkers; Epigenotoxicity; PBMC; PM(2.5).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Aging*
  • Air Pollutants / analysis
  • Air Pollution / adverse effects*
  • Carcinogenesis / chemically induced*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics
  • DNA Methylation
  • DNA Modification Methylases / genetics
  • DNA Repair Enzymes / genetics
  • Epigenesis, Genetic*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genetic Markers
  • Humans
  • Leukocytes, Mononuclear / metabolism
  • Male
  • Middle Aged
  • Particulate Matter / adverse effects
  • Promoter Regions, Genetic
  • Telomerase / metabolism
  • Telomere Shortening
  • Tumor Suppressor Proteins / genetics

Substances

  • Air Pollutants
  • Cyclin-Dependent Kinase Inhibitor p16
  • Genetic Markers
  • Particulate Matter
  • Tumor Suppressor Proteins
  • DNA Modification Methylases
  • MGMT protein, human
  • Telomerase
  • DNA Repair Enzymes