Is your environment making you older? Molecular biomarkers and new approaches to investigate the influences of environmental chemicals through aging

Main Article Content

Diddier Prada
Daniel Belsky
Andrea Baccarelli


Environment, Epigenetics, Age acceleration, Biological clocks, DNA methylation, Epitranscriptomics, Aging.


Aging is characterized by a gradual and progressive decline in system integrity that occurs with advancing chronological age. Although it is a physiological process, aging is associated with a myriad of age-related diseases (ARDs), including frailty, sarcopenia, chronic obstructive pulmonary disease, cardiovascular disease, cancer, and neurodegenerative diseases. While not exclusively ARDs, many of these diseases lead to death, a lesser quality of life, and increased healthcare costs for individuals and systems. ARDs share several underlying molecular mechanisms, such as cellular damage, inflammation, DNA methylation changes, stem cells exhaustion, and DNA mutations, which have been outlined as hallmarks of aging. Evidence suggests that environmental exposures, including but not limited to metals, air pollution, endocrine-disrupting chemicals, and noise, may accelerate biological aging. Over the past few years, aging research has identified new molecular biomarkers of the aging process. When applied to investigate environmental influences, these biomarkers can help identify individuals who are particularly susceptible to the influences of environmental exposures on aging processes and therefore guide in implementing possible preventive measures.


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1. Grimm SA, Shimbo T, Takaku M, et al. DNA methylation in mice is influenced by genetics as well as sex and life experience. Nat Commun. 2019;10(1):305. Published 2019 Jan 18. doi:10.1038/s41467-018-08067-z
2. Belsky DW, Caspi A, Arseneault L, et al. Quantification of the pace of biological aging in humans through a blood test, the DunedinPoAm DNA methylation algorithm. Elife. 2020;9:e54870. Published 2020 May 5. doi:10.7554/eLife.54870
3. Franceschi C, Garagnani P, Morsiani C, et al. The Continuum of Aging and Age-Related Diseases: Common Mechanisms but Different Rates. Front Med (Lausanne). 2018;5:61. Published 2018 Mar 12. doi:10.3389/ fmed.2018.00061
4. Cerella C, Grandjenette C, Dicato M, Diederich M. Roles of Apoptosis and Cellular Senescence in Cancer and Aging. Curr Drug Targets. 2016;17(4):405-415. doi: 10.2174/1389450116666150202155915
5. Cevenini E, Monti D, Franceschi C. Inflamm-ageing. Curr Opin Clin Nutr Metab Care. 2013;16(1):14- 20. doi:10.1097/MCO.0b013e32835ada13
6. Jones MJ, Goodman SJ, Kobor MS. DNA methylation and healthy human aging. Aging Cell. 2015;14(6):924- 932. doi:10.1111/acel.12349
7. de Haan G, Lazare SS. Aging of hematopoietic stem cells. Blood. 2018;131(5):479-487. doi:10.1182/ blood-2017-06-746412
8. Vijg J, Suh Y. Genome instability and aging. Annu Rev Physiol. 2013;75:645-668. doi:10.1146/annurev-physiol-030212-183715
9. Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194-1217. doi:10.1016/j.cell.2013.05.039
10. Mc Auley MT, Guimera AM, Hodgson D, et al. Modelling the molecular mechanisms of aging. Biosci Rep. 2017;37(1):BSR20160177. Published 2017 Feb 23. doi:10.1042/BSR20160177
11. Rappaport SM, Smith MT. Epidemiology. Environment and disease risks. Science. 2010;330(6003):460- 461. doi:10.1126/science.1192603
12. Prada D, Lopez G, Solleiro-Villavicencio H, Garcia- Cuellar C, Baccarelli AA. Molecular and cellular mechanisms linking air pollution and bone damage. Environ Res. 2020;185:109465. doi:10.1016/j.envres. 2020.109465
13. Prada D, Zhong J, Colicino E, et al. Association of air particulate pollution with bone loss over time and bone fracture risk: analysis of data from two independent studies. Lancet Planet Health. 2017;1(8):e337-e347. doi:10.1016 S2542-5196(17)30136-5
14. Kulick ER, Wellenius GA, Boehme AK, et al. Long-term exposure to air pollution and trajectories of cognitive decline among older adults. Neurology. 2020;94(17):e1782- e1792. doi:10.1212/WNL.0000000000009314
15. Lipfert FW, Wyzga RE. Longitudinal relationships between lung cancer mortality rates, smoking, and ambient air quality: a comprehensive review and analysis. Crit Rev Toxicol. 2019;49(9):790-818. doi:10.1080/10408444.2019.1700210
16. Hutchison K, Smith S, Faruqui S. The use of MODIS data and aerosol products for air quality prediction. Atmospheric Environment. 2004;38: 5057-5070. DOI: 10.1016/j.atmosenv.2004.06.032
17. Baccarelli AA, Hales N, Burnett RT, et al. Particulate Air Pollution, Exceptional Aging, and Rates of Centenarians: A Nationwide Analysis of the United States, 1980- 2010. Environ Health Perspect. 2016;124(11):1744- 1750. doi:10.1289/EHP197
18. Prada D, Gonzalez R, Sanchez L, Castro C, Fabian E, Herrera LA. Satellite 2 demethylation induced by 5-azacytidine is associated with missegregation of chromosomes 1 and 16 in human somatic cells. Mutat Res. 2012;729(1-2):100-105. doi:10.1016/j.mrfmmm. 2011.10.007
19. Zhong J, Karlsson O, Wang G, et al. B vitamins attenuate the epigenetic effects of ambient fine particles in a pilot human intervention trial [published correction appears in Proc Natl Acad Sci U S A. 2017 Apr 18;114(16):E3367]. Proc Natl Acad Sci U S A. 2017;114(13):3503-3508. doi:10.1073/pnas.1618545114
20. Peng C, Bind MC, Colicino E, et al. Particulate Air Pollution and Fasting Blood Glucose in Nondiabetic Individuals: Associations and Epigenetic Mediation in the Normative Aging Study, 2000-2011. Environ Health Perspect. 2016;124(11):1715-1721. doi:10.1289/EHP183
21. Carmona JJ, Sofer T, Hutchinson J, et al. Short-term airborne particulate matter exposure alters the epigenetic landscape of human genes associated with the mitogen- activated protein kinase network: a cross-sectional study. Environ Health. 2014;13:94. Published 2014 Nov 13. doi:10.1186/1476-069X-13-94
22. Rusiecki JA, Beane Freeman LE, Bonner MR, et al. High pesticide exposure events and DNA methylation among pesticide applicators in the agricultural health study. Environ Mol Mutagen. 2017;58(1):19-29. doi:10.1002/em.22067
23. Colicino E, Just A, Kioumourtzoglou MA, et al. Blood DNA methylation biomarkers of cumulative lead exposure in adults [published online ahead of print, 2019 Oct 21]. J Expo Sci Environ Epidemiol. 2019;10.1038/ s41370-019-0183-9. doi:10.1038/s41370-019-0183-9
24. Nwanaji-Enwerem JC, Colicino E. DNA Methylation-Based Biomarkers of Environmental Exposures for Human Population Studies. Curr Environ Health Rep. 2020;7(2):121-128. doi:10.1007/s40572-020-00269-2
25. Kennedy BK, Berger SL, Brunet A, et al. Geroscience: linking aging to chronic disease. Cell. 2014;159(4):709-713. doi:10.1016/j.cell.2014.10.039
26. Blackburn EH, Greider CW, Szostak JW. Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging. Nat Med. 2006;12(10):1133-1138. doi:10.1038/nm1006-1133
27. Holly AC, Melzer D, Pilling LC, et al. Towards a gene expression biomarker set for human biological age. Aging Cell. 2013;12(2):324-326. doi:10.1111/acel.12044
28. Peters MJ, Joehanes R, Pilling LC, et al. The transcriptional landscape of age in human peripheral blood. Nat Commun. 2015;6:8570. Published 2015 Oct 22. doi:10.1038/ncomms9570
29. Krištić J, Vučković F, Menni C, et al. Glycans are a novel biomarker of chronological and biological ages. J Gerontol A Biol Sci Med Sci. 2014;69(7):779-789. doi:10.1093/ gerona/glt190
30. Belsky DW, Caspi A, Houts R, et al. Quantification of biological aging in young adults. Proc Natl Acad Sci USA. 2015;112(30):E4104-E4110. doi:10.1073/pnas.1506264112
31. Jylhava J, Pedersen NL, Hagg S. Biological Age Predictors. EBioMedicine. 2017;21:29-36. doi:10.1016j.ebiom.2017.03.046
32. Jazwinski SM, Kim S. Examination of the Dimensions of Biological Age. Front Genet. 2019;10:263. Published
2019 Mar 26. doi:10.3389/fgene.2019.00263
33. Hannum G, Guinney J, Zhao L, et al. Genomewide methylation profiles reveal quantitative views of human aging rates. Mol Cell. 2013;49(2):359-367. doi:10.1016/j.molcel.2012.10.016
34. Horvath S. DNA methylation age of human tissues and cell types [published correction appears in Genome Biol. 2015;16:96]. Genome Biol. 2013;14(10):R115. doi:10.1186/gb-2013-14-10-r115
35. Horvath S, Raj K. DNA methylation-based biomarkers and the epigenetic clock theory of ageing. Nat Rev Genet. 2018;19(6):371-384. doi:10.1038/s41576-018-0004-3
36. Gao X, Colicino E, Shen J, et al. Accelerated DNA methylation age and the use of antihypertensive medication among older adults [published correction appears in Aging (Albany NY). 2019 May 15;11(9):2911]. Aging (Albany NY). 2018;10(11):3210-3228. doi:10.18632/aging.101626
37. Ward-Caviness CK, Nwanaji-Enwerem JC, Wolf K, et al. Long-term exposure to air pollution is associated with biological aging. Oncotarget. 2016;7(46):74510-74525. doi:10.18632/oncotarget.12903
38. Hou L, Wang S, Dou C, et al. Air pollution exposure and telomere length in highly exposed subjects in Beijing, China: a repeated-measure study. Environ Int. 2012;48:71-77. doi:10.1016/j.envint.2012.06.020
39. Marioni RE, Shah S, McRae AF, et al. DNA methylation age of blood predicts all-cause mortality in later life. Genome Biol. 2015;16(1):25. Published 2015 Jan 30. doi:10.1186/s13059-015-0584-6
40. White AJ, Kresovich JK, Keller JP, Xu Z, Kaufman JD, Weinberg CR, Taylor JA, Sandler DP. Air pollution, particulate matter composition and methylationbased biologic age. Environ Int. 2019 Nov;132:105071. doi: 10.1016/j.envint.2019.105071. Epub 2019 Aug 3. PMID: 31387022; PMCID: PMC6754788.
41. Nwanaji-Enwerem JC, Weisskopf MG, Baccarelli AA. Multi-tissue DNA methylation age: Molecular relationships and perspectives for advancing biomarker utility. Ageing Res Rev. 2018;45:15-23. doi:10.1016/j.arr.2018.04.005
42. Agha G, Mendelson MM, Ward-Caviness CK, et al. Blood Leukocyte DNA Methylation Predicts Risk of Future Myocardial Infarction and Coronary Heart Disease. Circulation. 2019;140(8):645-657. doi:10.1161CIRCULATIONAHA.118.039357
43. Barbieri I, Kouzarides T. Role of RNA modifications in cancer. Nat Rev Cancer. 2020;20(6):303-322. doi:10.1038/s41568-020-0253-2
44. Casella G, Tsitsipatis D, Abdelmohsen K, Gorospe M. mRNA methylation in cell senescence. Wiley Interdiscip Rev RNA. 2019;10(6):e1547. doi:10.1002/wrna.1547
45. Kupsco A, Gonzalez G, Baker BH, et al. Associations of smoking and air pollution with peripheral blood RNA N6-methyladenosine in the Beijing truck driver air pollution study. Environ Int. 2020;144:106021. doi:10.1016/j.envint.2020.106021
46. Lim SM, Choi JW, Hong MH, et al. Indoor radon exposure increases tumor mutation burden in never-smoker patients with lung adenocarcinoma. Lung Cancer. 2019;131:139-146. doi:10.1016/j.lungcan.2019.04.002
47. Risques RA, Kennedy SR. Aging and the rise of somatic cancer-associated mutations in normal tissues. PLoS Genet. 2018;14(1):e1007108. Published 2018 Jan 4. doi:10.1371/journal.pgen.1007108
48. Yizhak K, Aguet F, Kim J, et al. RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues. Science. 2019;364(6444):eaaw0726. doi: 10.1126/science.aaw0726
49. Alexandrov LB, Ju YS, Haase K, et al. Mutational signatures associated with tobacco smoking in human cancer. Science. 2016;354(6312):618-622. doi:10.1126/science. aag0299
50. Somers CM, Yauk CL, White PA, Parfett CL, Quinn JS. Air pollution induces heritable DNA mutations. Proc Natl Acad Sci U S A. 2002;99(25):15904-15907. doi:10.1073/pnas.252499499
51. Agudelo-Casta.eda DM, Teixeira EC, Schneider IL, Lara SR, Silva LFO. Exposure to polycyclic aromatic hydrocarbons in atmospheric PM1.0 of urban environments: Carcinogenic and mutagenic respiratory health risk by age groups. Environ Pollut. 2017;224:158-170. doi:10.1016/j.envpol.2017.01.075
52. Justice JN, Ferrucci L, Newman AB, et al. A framework for selection of blood-based biomarkers for geroscienceguided clinical trials: report from the TAME Biomarkers Workgroup. Geroscience.