Abstract
Purpose of Review
Innovations in agriculture and medicine as well as industrial and domestic technologies are essential for the growing and aging global population. These advances generally require the use of novel natural or synthetic chemical agents with the potential to affect human health. Here, we attempt to highlight environmental chemicals and select drugs with the potential to exacerbate aging by directly affecting molecular aging cascades focusing particular attention on the brain. Finally, we call attention to some potential fruitful areas of research, particularly with advanced molecular profiling that could aid in prevention or mitigation of environmental chemical toxic influences in the periphery and the brain.
Recent Findings
We briefly summarize new research and highlight a recent study designed to prospectively identify agrochemicals with the potential to induce neurological diseases and place these discoveries into the already rich neurodegeneration and aging literature.
Summary
Collectively, the research reviewed briefly here highlight chemicals with the true potential to accelerate aging, particularly in the brain, by eliciting elevated free radical stress and mitochondrial dysfunction. We make general recommendations about improved methodological approaches toward identification and regulation of chemicals that are gerontogenic to the brain.
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References
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
•• Lopez-Otin C, Blasco MA, Partridge L, Serrano M, Kroemer G. The hallmarks of aging. Cell. 2013;153(6):1194–217. An essential review distinguishing the biological hallmarks of aging
Perls T, Puca A. The genetics of aging—implications for pharmacogenomics. Pharmacogenomics. 2002;3(4):469–84.
Grandjean P, Landrigan PJ. Neurobehavioural effects of developmental toxicity. Lancet Neurol. 2014;13(3):330–8.
EEA. Chemicals in the European Environment: Low Doses, High Stakes? the EEA and UNEP Annual Message 2 on the State of Europe’s Environment. 1998:32.
•• Sorrentino JA, Sanoff HK, Sharpless NE. Defining the toxicology of aging. Trends Mol Med. 2014;20(7):375–84. This review expertly articulates the concept of a gerontogen and aging biology and summarizes prominent gerontogen candidates as well as critical parameters for their discovery
Sanoff HK, Deal AM, Krishnamurthy J, Torrice C, Dillon P, Sorrentino J, et al. Effect of cytotoxic chemotherapy on markers of molecular age in patients with breast cancer. J Natl Cancer Inst. 2014;106(4):dju057.
Martin GM. Interactions of aging and environmental agents: the gerontological perspective. Prog Clin Biol Res. 1987;228:25–80.
Bondy SC. Anthropogenic pollutants may increase the incidence of neurodegenerative disease in an aging population. Toxicology. 2016;341-343:41–6.
Neff F, Flores-Dominguez D, Ryan DP, Horsch M, Schroder S, Adler T, et al. Rapamycin extends murine lifespan but has limited effects on aging. J Clin Invest. 2013;123(8):3272–91.
• Lu T, Pan Y, Kao SY, Li C, Kohane I, Chan J, et al. Gene regulation and DNA damage in the ageing human brain. Nature. 2004;429(6994):883–91. This study carefully examined postmortem forebrain transcriptomes as a function of age. In doing so, these researchers defined sets of up- and downregulated genes in aging thereby improving the field of aging neurobiology
Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.
Rikans LE, Hornbrook KR. Lipid peroxidation, antioxidant protection and aging. Biochim Biophys Acta. 1997;1362(2–3):116–27.
Alexander P. The role of DNA lesions in the processes leading to aging in mice. Symp Soc Exp Biol. 1967;21:29–50.
Cuervo AM, Dice JF. Age-related decline in chaperone-mediated autophagy. J Biol Chem. 2000;275(40):31505–13.
Cooke MS, Evans MD, Dizdaroglu M, Lunec J. Oxidative DNA damage: mechanisms, mutation, and disease. FASEB J. 2003;17(10):1195–214.
Wang X, Michaelis ML, Michaelis EK. Functional genomics of brain aging and Alzheimer’s disease: focus on selective neuronal vulnerability. Curr Genomics. 2010;11(8):618–33.
Wetmore BA, Wambaugh JF, Ferguson SS, Sochaski MA, Rotroff DM, Freeman K, et al. Integration of dosimetry, exposure, and high-throughput screening data in chemical toxicity assessment. Toxicol Sci. 2012;125(1):157–74.
Rotroff DM, Wetmore BA, Dix DJ, Ferguson SS, Clewell HJ, Houck KA, et al. Incorporating human dosimetry and exposure into high-throughput in vitro toxicity screening. Toxicol Sci. 2010;117(2):348–58.
Madani FZ, Hafida M, Merzouk SA, Loukidi B, Taouli K, Narce M. Hemostatic, inflammatory, and oxidative markers in pesticide user farmers. Biomarkers. 2016;21(2):138–45.
Pearson BL, Simon JM, McCoy ES, Salazar G, Fragola G, Zylka MJ. Identification of chemicals that mimic transcriptional changes associated with autism, brain aging and neurodegeneration. Nat Commun. 2016;7:11173.
Tanner CM, Kamel F, Ross GW, Hoppin JA, Goldman SM, Korell M, et al. Rotenone, paraquat, and Parkinson’s disease. Environ Health Perspect. 2011;119(6):866–72.
Sherer TB, Richardson JR, Testa CM, Seo BB, Panov AV, Yagi T, et al. Mechanism of toxicity of pesticides acting at complex I: relevance to environmental etiologies of Parkinson’s disease. J Neurochem. 2007;100(6):1469–79.
Krishnamurthy J, Torrice C, Ramsey MR, Kovalev GI, Al-Regaiey K, Su L, et al. Ink4a/Arf expression is a biomarker of aging. J Clin Invest. 2004;114(9):1299–307.
Tsygankov D, Liu Y, Sanoff HK, Sharpless NE, Elston TC. A quantitative model for age-dependent expression of the p16INK4a tumor suppressor. Proc Natl Acad Sci U S A. 2009;106(39):16562–7.
Martin N, Beach D, Gil J. Ageing as developmental decay: insights from p16(INK4a.). Trends Mol Med. 2014;20(12):667–74.
Lu T, Aron L, Zullo J, Pan Y, Kim H, Chen Y, et al. REST and stress resistance in ageing and Alzheimer’s disease. Nature. 2014;507(7493):448–54.
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):1133–8.
Daniali L, Benetos A, Susser E, Kark JD, Labat C, Kimura M, et al. Telomeres shorten at equivalent rates in somatic tissues of adults. Nat Commun. 2013;4:1597.
Hou L, Andreotti G, Baccarelli AA, Savage S, Hoppin JA, Sandler DP, et al. Lifetime pesticide use and telomere shortening among male pesticide applicators in the agricultural health study. Environ Health Perspect. 2013;121(8):919–24.
Andreotti G, Hoppin JA, Hou L, Koutros S, Gadalla SM, Savage SA, et al. Pesticide use and relative leukocyte telomere length in the agricultural health study. PLoS One. 2015;10(7):e0133382.
Kahl VF, Simon D, Salvador M, Branco Cdos S, Dias JF, da Silva FR, et al. Telomere measurement in individuals occupationally exposed to pesticide mixtures in tobacco fields. Environ Mol Mutagen. 2016;57(1):74–84.
Carlson ME, Conboy IM. Loss of stem cell regenerative capacity within aged niches. Aging Cell. 2007;6(3):371–82.
Boyd WA, Smith MV, Co CA, Pirone JR, Rice JR, Shockley KR, et al. Developmental effects of the ToxCast phase I and phase II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environ Health Perspect. 2016;124(5):586–93.
Bigarella CL, Liang R, Ghaffari S. Stem cells and the impact of ROS signaling. Development. 2014;141(22):4206–18.
Pereira SL, Graos M, Rodrigues AS, Anjo SI, Carvalho RA, Oliveira PJ, et al. Inhibition of mitochondrial complex III blocks neuronal differentiation and maintains embryonic stem cell pluripotency. PLoS One. 2013;8(12):e82095.
Mandal S, Lindgren AG, Srivastava AS, Clark AT, Banerjee U. Mitochondrial function controls proliferation and early differentiation potential of embryonic stem cells. Stem Cells. 2011;29(3):486–95.
Malik S, Vinukonda G, Vose LR, Diamond D, Bhimavarapu BB, Hu F, et al. Neurogenesis continues in the third trimester of pregnancy and is suppressed by premature birth. J Neurosci. 2013;33(2):411–23.
Huttenlocher PR, Dabholkar AS. Regional differences in synaptogenesis in human cerebral cortex. J Comp Neurol. 1997;387(2):167–78.
Tau GZ, Peterson BS. Normal development of brain circuits. Neuropsychopharmacology. 2010;35(1):147–68.
Mattson MP, Magnus T. Ageing and neuronal vulnerability. Nat Rev Neurosci. 2006;7(4):278–94.
Kole AJ, Annis RP, Deshmukh M. Mature neurons: equipped for survival. Cell Death Dis. 2013;4:e689.
Sykora P, Yang JL, Ferrarelli LK, Tian J, Tadokoro T, Kulkarni A, et al. Modulation of DNA base excision repair during neuronal differentiation. Neurobiol Aging. 2013;34(7):1717–27.
Laughlin SB, de Ruyter van Steveninck RR, Anderson JC. The metabolic cost of neural information. Nat Neurosci. 1998;1(1):36–41.
Russell WMS, Burch RL. The principles of humane experimental technique. London. Methuen. 1959:238.
Oeppen J, Vaupel JW. Demography. Broken limits to life expectancy. Science. 2002;296(5570):1029–31.
Fu G, Dai J, Zhang D, Zhu L, Tang X, Zhang L, et al. 2016 Di(2-ethylhexyl) phthalate induces apoptosis through mitochondrial pathway in GC-2spd cells. Environ Toxicol.
Ore A, Olayinka ET. 2016 Fluazifop-p-butyl, an aryloxyphenoxypropionate herbicide, diminishes renal and hepatic functions and triggers testicular oxidative stress in orally exposed rats. Toxicol Ind Health.
Kazemi S, Mousavi SN, Aghapour F, Rezaee B, Sadeghi F, Moghadamnia AA. Induction effect of bisphenol A on gene expression involving hepatic oxidative stress in rat. Oxidative Med Cell Longev. 2016;2016:6298515.
Jang TC, Jang JH, Lee KW. Mechanism of acute endosulfan intoxication-induced neurotoxicity in Sprague-Dawley rats/Mehanizam akutne neurotoksicnosti u Sprague-Dawley stakora izazvane trovanjem endosulfanom. Arh Hig Rada Toksikol. 2016;67(1):9–17.
Qiu W, Chen J, Li Y, Chen Z, Jiang L, Yang M, et al. Oxidative stress and immune disturbance after long-term exposure to bisphenol A in juvenile common carp (Cyprinus carpio). Ecotoxicol Environ Saf. 2016;130:93–102.
Duan P, Hu C, Butler HJ, Quan C, Chen W, Huang W, et al. 2016 4-Nonylphenol induces disruption of spermatogenesis associated with oxidative stress-related apoptosis by targeting p53-Bcl-2/Bax-Fas/FasL signaling. Environ Toxicol.
Jin X, Coughlan M, Roberts J, Mehta R, Raju J. Dietary acrylamide exposure in male F344 rats: dataset of systemic oxidative stress and inflammation markers. Data Brief. 2016;7:460–7.
Ma T, Chen L, Wu L, Zhang H, Luo Y. Oxidative stress, cytotoxicity and genotoxicity in earthworm Eisenia fetida at different di-n-butyl phthalate exposure levels. PLoS One. 2016;11(3):e0151128.
Ilavenil S, Al-Dhabi NA, Srigopalram S, Ock Kim Y, Agastian P, Baru R, et al. Acetaminophen induced hepatotoxicity in Wistar rats—a proteomic approach. Molecules. 2016;21(2):161.
Zhang JQ, Gao BW, Wang J, Wang XW, Ren QL, Chen JF, et al. Chronic exposure to diquat causes reproductive toxicity in female mice. PLoS One. 2016;11(1):e0147075.
Charvatova N, Zelinska G, Dobsikova R, Stancova V, Zivna D, Plhalova L, et al. The effect of the fluoroquinolone norfloxacin on somatic indices and oxidative stress parameters in early stages of common carp (Cyprinus carpio L.). Neuro Endocrinol Lett. 2015;36(Suppl 1):79–87.
Lefevre PL, Berger RG, Ernest SR, Gaertner DW, Rawn DF, Wade MG, et al. Exposure of female rats to an environmentally relevant mixture of brominated flame retardants targets the ovary. Affecting Folliculogenesis and Steroidogenesis Biol Reprod. 2016;94(1):9.
Tao S, Zhang Y, Yuan C, Gao J, Wu F, Wang Z. Oxidative stress and immunotoxic effects of bisphenol A on the larvae of rare minnow Gobiocypris rarus. Ecotoxicol Environ Saf. 2016;124:377–85.
Song Q, Zheng P, Qiu L, Jiang X, Zhao H, Zhou H, et al. Toxic effects of male Perna viridis gonad exposed to BaP, DDT and their mixture: a metabolomic and proteomic study of the underlying mechanism. Toxicol Lett. 2016;240(1):185–95.
Abolaji AO, Toloyai PE, Odeleye TD, Akinduro S, Teixeira Rocha JB, Farombi EO. Hepatic and renal toxicological evaluations of an industrial ovotoxic chemical, 4-vinylcyclohexene diepoxide, in both sexes of Wistar rats. Environ Toxicol Pharmacol. 2016;45:28–40.
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Brandon L. Pearson and Dan Ehninger declare that they have no conflict of interest.
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This article does not include data from any original/unpublished studies. However, this review refers to published work by both authors which was performed under appropriate institutional ethical approval.
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Pearson, B.L., Ehninger, D. Environmental Chemicals and Aging. Curr Envir Health Rpt 4, 38–43 (2017). https://doi.org/10.1007/s40572-017-0131-6
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DOI: https://doi.org/10.1007/s40572-017-0131-6