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telomere

Function: - complex of DNA & protein that constitute the caps of chromosome ends - telomeres function as a buffer to prevent loss of genomic sequence information during replication (see telomerase) - loss of telomeres provides a mechanism of cellular senescence & protection against malignant transformation Structure: - in humans, telomeres consist of a 5-15 kilobase repeated array of the sequence TTAGGG - telomeres are protected by a capping protein that binds single stranded DNA - capping protein may include rad51B, RAP1 & TRTF2. Pathology: 1) increased mortality in patients with dementia correlates with lesser telomere length in peripheral blood leukocytes [4] (it is difficult to envision a mechanism) 2) shorter telomere length in peripheral blood mononuclear cells a) allegedly predicts cognitive decline, dementia & death after stroke [5] - difficult to envision mechanism b) independent predictor of coronary artery disease [6] again, - difficult to envision mechanism 3) shorter telomere length in leukocytes is associated with increased risk of cancer & mortality [8,17] 4) shorter telomere length in peripheral blood leukocytes is associated with increased cardiovascular risk [14] again, - difficult to envision mechanism 5) shorter telomere length & greater telomerase activity in leukocytes of men with hostility [11] 6) telomere length in leukocytes predicts susceptibility to upper respiratory tract infections in young adults [12] 7) shorter telomere length in patients with depression [13] 8) shorter leukjocyte telomere length is associated with increased morality [17] 9) shortening of telomeres does not play a causative role in aging [16] 10) leukocyte telomere length of 5 kb defined as telomeric brink - a subset of adults may reach the telomeric brink within 100 years [18] Physiology: - longer telomere length in peripheral blood mononuclear cells - associated with heavy exercise - telomere dysfunction activates p53-mediated cellular growth arrest, senescence & apoptosis to drive progressive atrophy & functional decline in high-turnover tissues [9] Comparative biology: - in mice null for either telomerase reverse transcriptase (Tert) or telomerase RNA component (Terc) genes, repression of PPAR-gamma & its coactivators Ppargc1a & Ppargc1b inhibit mitochondrial biogenesis & function [9]

Related

POT1 protein (protection of telomeres 1, POT1-like telomere end-binding protein) telomerase telomeres & telomerase in tumor cells

General

macromolecular complex

Properties

References

  1. de Lange T Cell biology. Telomere capping--one strand fits all. Science 292:1075-6 2001 PMID: 11352055
  2. Baumann P & Cech TR. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292:1171-5 2001 PMID: 11349150
  3. Hoeijmakers JH Genome maintenance mechanisms for preventing cancer. Nature 411:366, 2001 PMID: 11357144
  4. Honig LS et al, Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia. Ann Neurol 2006, 60:181 PMID: 16807921
  5. Martin-Ruiz C et al, Telomer length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol 2006, 60:174 PMID: 16685698
  6. Brouilette SW et al, Telomere length, risk of coronary artery disease, and statin treatment in the West of Scottlan Primary Prevention Study: A nested case-control study. Lancet 2007, 369:107 PMID: 17223473
  7. Cherkas LF et al, The association between physical activity in leisure time and leukocyte telomer length. Arch Intern Med 2008, 168:154 PMID: 18227361
  8. Willeit P Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010 Jul 7;304(1):69-75. PMID: 20606151
  9. Sahin E et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011 Feb 17; 470:359 PMID: 21307849
  10. Mather KA. Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci 2011; 66(2):202-213. PMID: 21030466
  11. Brydon L et al. Hostility and cellular aging in men from the Whitehall II cohort. Biol Psychiatry 2012 May 1; 71:767. PMID: 21974787
  12. Cohen S et al. Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. JAMA 2013 Feb 20; 309:699. PMID: 23423415
  13. Verhoeven JE et al. Major depressive disorder and accelerated cellular aging: Results from a large psychiatric cohort study. Mol Psychiatry 2013 Nov 12 PMID: 24217256
  14. Haycock PC et al. Leucocyte telomere length and risk of cardiovascular disease: Systematic review and meta-analysis. BMJ 2014 Jul 8; 349:g4227 PMID: 25006006 http://www.bmj.com/content/349/bmj.g4227
  15. Cong Y, Shay JW Actions of human telomerase beyond telomeres. Cell Research (2008) 18:725-732 PMID: 18574498 http://www.nature.com/cr/journal/v18/n7/full/cr200874a.html
  16. Simons MJ Questioning causal involvement of telomeres in aging. Ageing Res Rev. 2015 Aug 21 PMID: 26304838
  17. Arbeev KG, Verhulst S, Steenstrup T et al Association of Leukocyte Telomere Length With Mortality Among Adult Participants in 3 Longitudinal Studies. JAMA Netw Open. 2020;3(2):e200023. PMID: 32101305 Free Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2761863
  18. Steenstrup T, Kark JD, Verhulst S et al Telomeres and the natural lifespan limit in humans. Aging (Albany NY). 2017 Apr;9(4):1130-1142. PMID: 28394764 Free PMC Article

Component-of

non human chromosome