External environmental agents influence telomere length and telomerase activity by modulating internal cellular processes: Implications in human aging
Authors: Rebecca Dsouza
Stina George Fernandes
Ekta Khattar
Journal: Environmental Toxicology and Pharmacology (2021)
Discipline: PHARMACOLOGY & TOXICOLOGY
Keywords: Environmental agents; Inflammation; Oxidative stress; Telomerase; Telomere length.
Affiliations: Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Vile Parle West, Mumbai, 400056, India., Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Vile Parle West, Mumbai, 400056, India. Electronic address: .

Abstract:  External environment affects cellular physiological processes and impact the stability of our genome. The most important structural components of our linear chromosomes which endure the impact by these agents, are the chromosomal ends called telomeres. Telomeres preserve the integrity of our genome by preventing end to end fusions and telomeric loss through by inhibiting DNA damage response (DDR) activation. This is accomplished by the presence of a six membered shelterin complex at telomeres. Further, telomeres cannot be replicated by normal DNA polymerase and require a special enzyme called telomerase which is expressed only in stem cells, few immune cells and germ cells. Telomeres are rich in guanine content and thus become extremely prone to damage arising due to physiological processes like oxidative stress and inflammation. External environmental factors which includes various physical, biological and chemical agents also affect telomere homeostasis by increasing oxidative stress and inflammation. In the present review, we highlight the effect of these external factors on telomerase activity and telomere length. We also discuss how the external agents affect the physiological processes, thus modulating telomere stability. Further, we describe its implication in the development of aging and its related pathologies. 

Retracted: No

PubPeer comments:
 1 . Introduction, last paragraph: The authors state that  we comprehensively describe the role of physiological processes like oxidative stress and inflammatory response in modulating the length of telomere and the activity of telomerase - this is not correct as the authors do not describe these processes in this articles as this is not a research article, they just review the published articles on the processes. If they are going to describe the processes, are they showing any primary research data in this article? 2.  We discuss how various external environmental agents impact these physiological processes and affect telomere homeostasis - again, they are discussing the association by reviewing the published articles but not discussing their primary research data. Therefore, the authors are not correct in stating those sentences in the last paragraph of Introduction section. 3. Section 2, Internal Cellular Processes 2.1.1 Oxidative stress modulates telomere length - couple of original reports from Dr V A Bohr s laboratory is not highlighted in this section -published earlier than 2002.. 4. 2.1.1 last sentence  However, in vivo observations in mice support the role of oxidative stress in telomere shortening - no citations here - this is not the conclusion from the authors previous studies. there are many instances where authors state the obvious without any reference to previous work. This is one example. 5. 3.1.1 Radiation: The authors selectively chose references in this review. One of the earliest observations missed on radiation effect on telomere in mice - 10.1016 s0027-5107(98)00115-8 (1999) and in cancer cells (10.1016 s0027-5107(97)00321-7 - 1998). 6. 3.2 Chemical Agents: There are sufficient number of publications to quote here on environmental arsenic exposure and effects on telomeres from West Bengal, India. a. Epigenetic regulations in alternative telomere lengthening: Understanding the mechanistic insight in arsenic-induced skin cancer patients. Bhattacharjee P, Das A, Giri AK, Bhattacharjee P. Sci Total Environ. 2020 Feb 20;704:135388. doi: 10.1016 j.scitotenv.2019.135388. Epub 2019 Nov 23. PMID: 31837846 b. Evaluation of health effects, genetic damage and telomere length in children exposed to arsenic in West Bengal, India. Chatterjee D, Adak S, Banerjee N, Bhattacharjee P, Bandyopadhyay AK, Giri AK. Mutat Res Genet Toxicol Environ Mutagen. 2018 Dec;836(Pt A):82-88. doi: 10.1016 j.mrgentox.2018.06.012. Epub 2018 Jun 7. PMID: 30389167 c. Arsenic exposure through drinking water leads to senescence and alteration of telomere length in humans: A case-control study in West Bengal, India. Chatterjee D, Bhattacharjee P, Sau TJ, Das JK, Sarma N, Bandyopadhyay AK, Roy SS, Giri AK. Mol Carcinog. 2015 Sep;54(9):800-9. doi: 10.1002 mc.22150. Epub 2014 Mar 24. PMID: 24665044 7. in the concluding remarks  Some of the studies report contradictory results, which could be understood if integrated with other biomarkers of telomere length regulation, for example, combining with genetic factors which are known to regulate telomere length or telomerase activity. - it would be good to highlight the other  biomarkers the authors kept on mentioning in the review. They fail to mention genome instability, chromosome instability which are the results of telomere dysfunction. 8. A matured view on the historical evidence and current prospects would have been idea. ,