telomere
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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
- increased mortality in patients with dementia correlates with lesser telomere length in peripheral blood leukocytes[4] (it is difficult to envision a mechanism)
- shorter telomere length in peripheral blood mononuclear cells
- allegedly predicts cognitive decline, dementia & death after stroke[5] - difficult to envision mechanism
- independent predictor of coronary artery disease[6] again, - difficult to envision mechanism
- shorter telomere length in leukocytes is associated with increased risk of cancer & mortality[8][17]
- shorter telomere length in peripheral blood leukocytes is associated with increased cardiovascular risk[14] again, - difficult to envision mechanism
- shorter telomere length & greater telomerase activity in leukocytes of men with hostility[11]
- telomere length in leukocytes predicts susceptibility to upper respiratory tract infections in young adults[12]
- shorter telomere length in patients with depression[13]
- shorter leukjocyte telomere length is associated with increased morality[17]
- shortening of telomeres does not play a causative role in aging[16]
- 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]
More general terms
Additional terms
- POT1 protein (protection of telomeres 1, POT1-like telomere end-binding protein)
- telomerase
- telomeres & telomerase in tumor cells
Component of
References
- ↑ de Lange T Cell biology. Telomere capping--one strand fits all. Science 292:1075-6 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11352055
- ↑ Baumann P & Cech TR. Pot1, the putative telomere end-binding protein in fission yeast and humans. Science 292:1171-5 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11349150
- ↑ Hoeijmakers JH Genome maintenance mechanisms for preventing cancer. Nature 411:366, 2001 PMID: https://www.ncbi.nlm.nih.gov/pubmed/11357144
- ↑ 4.0 4.1 Honig LS et al, Shorter telomeres are associated with mortality in those with APOE epsilon4 and dementia. Ann Neurol 2006, 60:181 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16807921
- ↑ 5.0 5.1 Martin-Ruiz C et al, Telomer length predicts poststroke mortality, dementia, and cognitive decline. Ann Neurol 2006, 60:174 PMID: https://www.ncbi.nlm.nih.gov/pubmed/16685698
- ↑ 6.0 6.1 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: https://www.ncbi.nlm.nih.gov/pubmed/17223473
- ↑ Cherkas LF et al, The association between physical activity in leisure time and leukocyte telomer length. Arch Intern Med 2008, 168:154 PMID: https://www.ncbi.nlm.nih.gov/pubmed/18227361
- ↑ 8.0 8.1 Willeit P Telomere length and risk of incident cancer and cancer mortality. JAMA. 2010 Jul 7;304(1):69-75. PMID: https://www.ncbi.nlm.nih.gov/pubmed/20606151
- ↑ 9.0 9.1 9.2 Sahin E et al. Telomere dysfunction induces metabolic and mitochondrial compromise. Nature 2011 Feb 17; 470:359 PMID: https://www.ncbi.nlm.nih.gov/pubmed/21307849
- ↑ Mather KA. Is telomere length a biomarker of aging? A review. J Gerontol A Biol Sci Med Sci 2011; 66(2):202-213. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21030466
- ↑ 11.0 11.1 Brydon L et al. Hostility and cellular aging in men from the Whitehall II cohort. Biol Psychiatry 2012 May 1; 71:767. PMID: https://www.ncbi.nlm.nih.gov/pubmed/21974787
- ↑ 12.0 12.1 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: https://www.ncbi.nlm.nih.gov/pubmed/23423415
- ↑ 13.0 13.1 Verhoeven JE et al. Major depressive disorder and accelerated cellular aging: Results from a large psychiatric cohort study. Mol Psychiatry 2013 Nov 12 PMID: https://www.ncbi.nlm.nih.gov/pubmed/24217256
- ↑ 14.0 14.1 Haycock PC et al. Leucocyte telomere length and risk of cardiovascular disease: Systematic review and meta-analysis. BMJ 2014 Jul 8; 349:g4227 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/25006006 <Internet> http://www.bmj.com/content/349/bmj.g4227
- ↑ Cong Y, Shay JW Actions of human telomerase beyond telomeres. Cell Research (2008) 18:725-732 <PubMed> PMID: https://www.ncbi.nlm.nih.gov/pubmed/18574498 <Internet> http://www.nature.com/cr/journal/v18/n7/full/cr200874a.html
- ↑ 16.0 16.1 Simons MJ Questioning causal involvement of telomeres in aging. Ageing Res Rev. 2015 Aug 21 PMID: https://www.ncbi.nlm.nih.gov/pubmed/26304838
- ↑ 17.0 17.1 17.2 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: https://www.ncbi.nlm.nih.gov/pubmed/32101305 Free Article https://jamanetwork.com/journals/jamanetworkopen/fullarticle/2761863
- ↑ 18.0 18.1 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: https://www.ncbi.nlm.nih.gov/pubmed/28394764 Free PMC Article