Telomere dynamics and cellular senescence: an emerging field in environmental and occupational toxicology

Abstract

There has been a steady output of epidemiological studies linking environmental and occupational exposures to altered telomere length, showing mainly positive associations with persistent organic pollutants, inverse association with cadmium and inconsistent results with arsenic and lead. A bell-shaped dose–response relationship has been observed for ionizing radiation with telomere shortening at a low dose. Long-term air pollution is associated with telomere shortening, whereas the short-term exposure studies have shown mixed results. There are surprisingly few studies on telomere dynamics in animals. Studies on telomere dynamics and senescence in target tissues of animal strains used in toxicology are warranted. Cell culture studies on ionizing radiation have shown mixed results on telomere length, whereas both telomerase activity and cellular senescence are increased. Studies on persistent organic pollutants indicate telomere shortening, decreased telomerase activity and increased cellular senescence. Cell culture studies on heavy metals and air pollution particles are inconsistent. There is no coherent relationship between exposures, oxidative stress, telomere length, telomerase activity and cellular senescence in experimental studies on environmental or occupational exposures. This may be due to differences in exposure levels (including dose rate), exposure time and models (i.e. cell types and animal strains). Guidelines are needed for best practices on assays for telomere dynamics and cellular senescence in toxicology. However, it deserves notice that experimental studies in cells and animals have revealed important information on the effects of environmental and occupational agents on the maintenance of telomeres and cellular senescence.

Keywords:

• Particles
• heavy metals
• endocrine disruptors
• senescence
• telomere length

Acknowledgments

The authors express appreciation to the three external reviewers selected by the Editor and anonymous to the authors for their valuable comments. These comments were very useful in revising the original manuscript.

Declaration of interest

The authors have sole responsibility for the writing and content of the paper. The authors have sole responsibility for the conceptualization and conduct of the study and the conclusions and recommendations contained therein. None of the authors have appeared during the past 5 years in any legal or regulatory proceedings related to the contents of the paper. The authors report no conflict of interest relevant to this review article. The author’s affiliation is as shown on the cover page.

Additional information

Funding

This work was supported by the Danish Council of Independent Research [Medical Sciences, grant No. 6110–00103].