Abstract
We present a list of basic functions to ensure viability of living systems and highlight the roles that telomerase plays. Telomere length is an intrinsic determinant of cellular and perhaps organismal lifespan. The limitation of DNA polymerases in replicating the end of linear replication is partly taken care of by addition of hexanucleotide repeats at the end of the template strands by telomerase reverse transcriptase. Interaction of telomerase with other cellular molecules enables it to perform several extra-curricular functions. It is essential for dividing cells such as those of developing embryo, activated immune cells, activated stem cells, and cancerous cells, to have active telomerase in them. Telomere length is a qualifying feature to monitor cellular health and let it proceed along cell cycle, and hence telomerase takes the center stage and communicates with diverse cellular phenomena involving key regulators like transforming growth factor B, translationally controlled tumor protein, survivin, and p53. It is an anti-apoptotic factor and promotes cell survival. It also influences redox homoeostasis of cells. Genetic and environmental factors influencing telomerase expression can influence the aging process. We also comment on the relevance of telomerase as a therapeutic target in cancers that necessarily depend on maintenance of telomere length.
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References
Allsop R, Cheshier S, Weissman I. Telomerase reactivation and rejuvenation of telomere length in stimulated T cells derived from serially transplanted hematopoietic stem cells. J Exp Med. 2002;196:1427–33.
Artandi SE, Alson S, Tietze MK, Sharpless NE, Ye S, Greenberg RA, Castrillon DH, Horner JW, Weiler SR, Carrasco RD, DePinho RA. Constitutive telomerase expression promotes mammary carcinomas in aging mice. Proc Natl Acad Sci. 2002;99:8191–6.
Atzmon G, Cho M, Cawthon RM, Budagov T, Katz M, Yang X, Siegel G, et al. Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians. Proc Natl Acad Sci U S A. 2009;107:1–8.. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/19915151
Aubert G, Baerlocher GM, Vulto I, Poon SS, Lansdorp PM. Collapse of telomere homeostasis in hematopoietic cells caused by heterozygous mutations in telomerase genes. PLoS Genet. 2012;8(5):e1002696.
Banks W a, Morley JE, Farr S a, Price TO, Ercal N, Vidaurre I, Schally AV. Effects of a growth hormone-releasing hormone antagonist on telomerase activity, oxidative stress, longevity, and aging in mice. Proc Natl Acad Sci U S A. 2010;107:22272–7.
Barnea E, Bergman Y. Synergy of SF1 and RAR in activation of Oct-3/4 promoter. J Biol Chem. 2000;275:6608–19.
Bernardes de Jesus B, Vera E, Schneeberger K, Tejera AM, Ayuso E, Bosch F, Blasco MA. Telomerase gene therapy in adult and old mice delays aging and increases longevity without increasing cancer. EMBO Mol Med. 2012;4(8):691–704.
Blasco. Mice with bad ends: mouse models for studying telomeres and telomerase in cancer and aging. EMBO J. 2005;24:1095–103.
Blasco MA, Lee H-W, Hande MP, Samper E, Lansdorp PM, DePinho RA, Greider CW. Telomere shortening and tumor formation by mouse cells lacking telomerase RNA. Cell. 1997;91:25–34.
Bryan TM, Englezou A, Dalla-Pozza L, Dunham MA, Redell RR. Evidence for an alternative mechanism for maintaining telomere length in human tumors and tumor-derived cell lines. Nat Med. 1997;3:1271–4.
Carrel A. "On the Permanent Life of Tissues Outside of the Organism" (PDF). J Exp Med. 1912;15(5):516–28.
Cherkas LF, Aviv A, Valdes AM, Hunkin JL, Gardner JP, Surdulescu GL, Kimura M, Spector TD. The effects of social status on biological aging as measured by white-blood-cell telomere length. Aging Cell. 2006;5(2006):361–5.
Cowell JK. Telomeres and telomerase in ageing and cancer. Age (Omaha). 1999;22:59–64.
Daubenmier J, Lin J, Blackburn E, Hecht FM, Kristeller J, Maninger N, Kuwata M, et al. Changes in stress, eating, and metabolic factors are related to changes in telomerase activity in a randomized mindfulness intervention pilot study. Psychoneuroendocrinology. 2012;37(7):917–28.
Effros R. Telomerase induction in T cell: a cure for aging and disease. Exp Gerentol. 2007;42:416–20.
Effros RB. Telomere/telomerase dynamics within the human immune system: effect of chronic infection and stress. Exp Gerontol. 2011;46:135–40.
Epel ES, Blackburn EH, Lin J, Dhabhar FS, Adler NE, Morrow JD, Cawthon RM. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci U S A. 2004;101(2004):17312–5.
Espejel S, Klatt P, Murcia JM-D, MartÃn-Caballero J, Flores JM, Taccioli G, De Murcia G, Blasco MA. Impact of telomerase ablation on organismal viability aging and tumorigenesis in mice lacking the DNA repair proteins PARP1, Ku86 or DNAPKc. J Cell Biol. 2004;167:627–38.
Garcia CK, Wright WE, Shay JW. Human diseases of telomerase dysfunction: insights into tissue aging. Nucleic Acids Res. 2007;35:7406–16.
Gnanasekar M, Ramaswamy K. Translationally controlled tumor protein of Brugia malayi functions as an antioxidant protein. Parasitol Res. 2007;101:1533–40.
Goto S. Biological mechanisms of aging, a historical and critical overview. In: Mori N, Mook-Jung I, editors. Aging Mechanisms: Springer; 2015. https://doi.org/10.1007/978-4-431-55763-0_1.
Graidist P, Yazawa M, Tonganunt M, Nakatomi A, Lin CC, Chang J, Phongdara A, Fujise K. Fortilin binds Ca2+ and blocks Ca2+ dependent apoptosis in vivo. Biochem J. 2007;408:181–91.
Harley CB, Liu W, Blasco M, Vera E, Andrews WH, Briggs LA, Raffaele JM. A natural product telomerase activator as part of a health maintenance program. Rejuvenation Res. 2011;14(1):45–56.
Hayflick L, Moorhead P. The serial cultivation of human diploid cell strains. Exp Cell Res. 1961;25:585–621.
Hornsby P. Telomerase and aging process. Exp Gerontol. 2007;42:575–81.
Hummelke GC, Cooney AJ. Germ cell nuclear factor is a transcriptioinal repressor for embryonic development. Front Biosci. 2001;6:1186–91.
Jacob S, Shroeder P, Buechner N, Kunze K, Altschmeid J, Haendeler J. Nuclear Shp-2 keeps telomerase reverse transcriptase in the nucleus- new potential anti-aging target. Cell Commun Signal. 2009;7:A60. https://doi.org/10.1186/1478-811X-7-S1-A60.
Koziol MJ, Garrett N, Gurdon JB. Tpt1 activates transcription of oct4 and nanog in transplanted nuclei. Curr Biol. 2007;17:801–7.
LeMenuet PGD, Chung AC, Mancini M, Wheeler DA, Cooney AJ. Orphan nuclear receptor LRH-1 is required to maintain Oct4 expression at the epiblast stage of embryonic development. Mol Cell Biol. 2005;25:3492–505.
Lesur I, Campbell JL. The transcriptome of prematurely aging yeast cell is similar to that of telomerase-deficient cells. Mol Cell Biol. 2003;15:1297–312.
Lin PC, Chiou TW, Liu PY, Chen SP, Wang HI, Huang PC, Lin SZ, et al. Food supplement 20070721-GX may increase CD34+ stem cells and telomerase activity. J Biomed Biotechnol. 2012;2012:498051.
Lloyd AC. Limits to lifespan. Comment Nat Cell Biol. 2002;4:E25–7.
Meyerson M, Counter CM, Eaton ENG, Ellisen LW, Steiner P, Dickinson Caddie S, Ziaugra L, Beijersbergen RL, Davidoff MJ, Qingyun L, Bacchetti S, Haber DA, Weinberg RA. hEST2, the putative human telomerase catalytic subunit gene, is up-regulated in tumor cells and during immortalization. Cell. 1997;90:785–95.
Nicholls C, Pinto AR, Li H, Li L, Wang L, Simpson R, Liu J-P. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) induces cancer cell senescence by interacting with telomerase RNA component. Proc Natl Acad Sci. 2012;109(33):13308–13.
Njajou OT, Blackburn EH, Pawlikowska L, Mangino M, Damcott CM, Kwok PY, Spector TD, et al. A common variant in the telomerase RNA component is associated with short telomere length. PLoS One. 2010;5(9):e13048.
O’Connor MS, Carlson ME, Conboy IM. Differentiation rather than aging of muscle stem cells abolishes their telomerase activity. Biotechnol Prog. 2009;25:1130–7.
Ouellette MM, Wright WE, Shay JW. Targeting telomerase-expressing cancer cells. J Cell Mol Med. 2011;15:1433–42.
Pont AR, Sadri N, Hsiao SJ, Smith S, Schneider RJ. MRNA decay factor AUF1 maintains Normal aging, telomere maintenance, and suppression of senescence by activation of telomerase transcription. Mol Cell. 2012;47(1):5–15.
Ramakrishnan SK, Varshney A, Sharma A, Das BC, Yadava PK. Expression of targeted ribozyme against telomerase RNA causes altered expression of several other genes in tumor cells. Tumor Biol. 2014;35:5539–50.
Samper E, Flores J, Blasco M. Restoration of telomerase activity rescues chromosomal instability and premature aging in mice. EMBO Rep. 2001;2:800–7.
Schmedt T, Chen Y, Nguyen TT, Li S, Bonanno JA, Jurkunas UV. Telomerase immortalization of human corneal endothelial cells yields functional hexagonal monolayers. PLoS One. 2012;7(12):e51427.
Senthilkumar PK, Klingelhutz AJ, Jacobus JA, Lehmler H, Robertson LW, Ludewig G. Airborne polychlorinated biphenyls (PCBs) reduce telomerase activity and shorten telomere length in immortal human skin keratinocytes (HaCat). Toxicol Lett. 2011;204(1):64–70.
Song LL, Ponomareva L, Shen H, Duan X, Alimirah F, Choubey D. Interferon-inducible IFI16, a negative regulator of cell growth, down-regulates expression of human telomerase reverse transcriptase (hTERT) gene. PLoS One. 2010;5(1):e8569.
Soohoo CY, Shi R, Lee TH, Huang P, Lu KP, Zhou XZ. Telomerase inhibitor PinX1 provides a link between TRF1 and telomerase to prevent telomere elongation. J Biol Chem. 2011;286(5):3894–906.
Varshney AK, Ramkrishnan SK, Sharma AK, Santosh B, Bala J, Yadava PK. Global expression profile of telomerase-associated genes in HeLa cells. Gene. 2014;547:211–7.
Westin ER, Aykin-Burns N, Buckingham EM, Spitz DR, Goldman FD, Klingelhutz AJ. The p53/p21(WAF/CIP) pathway mediates oxidative stress and senescence in dyskeratosis congenita cells with telomerase insufficiency. Antioxid Redox Signal. 2011;14(6):985–97.
Zhang J, Tam WL, Tong GQ, Wu Q, Chan HY, Soh BS, Lou Y, Yang J, Ma Y, Chai L, et al. Sal4 modulates embryonic stem cell lpluripotency and early embryonic development by the transcriptional regulation of Pou5f1. Nat Cell Biol. 2006;8:1114–23.
Zhu J, Zhao Y, Wang S. Chromatin and epigenetic regulation of the telomerase reverse transcriptase gene. Protein Cell. 2010;1:22–32.
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Mishra, D.K., Prasad, R., Yadava, P. (2020). Telomeres, Telomerase, and Aging. In: Rath, P. (eds) Models, Molecules and Mechanisms in Biogerontology. Springer, Singapore. https://doi.org/10.1007/978-981-32-9005-1_7
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