Human telomere biology: A contributory and interactive factor in aging, disease risks, and protection

Telomeres are the protective end-complexes at the termini of eukaryotic chromosomes. Telomere attrition can lead to potentially maladaptive cellular changes, block cell division, and interfere with tissue replenishment. Recent advances in the understanding of human disease processes have clarified the roles of telomere biology, especially in diseases of human aging and in some aging-related processes. Greater overall telomere attrition predicts mortality and aging-related diseases in inherited telomere syndrome patients, and also in general human cohorts. However, genetically caused variations in telomere maintenance either raise or lower risks and progression of cancers, in a highly cancer type–specific fashion. Telomere maintenance is determined by genetic factors and is also cumulatively shaped by nongenetic influences throughout human life; both can interact. These and other recent findings highlight both causal and potentiating roles for telomere attrition in human diseases.

[1]  M. Haussmann,et al.  Telomere dynamics may link stress exposure and ageing across generations , 2015, Biology Letters.

[2]  S. Hägg,et al.  Telomere Length Shortening and Alzheimer Disease--A Mendelian Randomization Study. , 2015, JAMA neurology.

[3]  S. Savage,et al.  Unraveling the pathogenesis of Hoyeraal–Hreidarsson syndrome, a complex telomere biology disorder , 2015, British journal of haematology.

[4]  O. Wolkowitz,et al.  Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging , 2015, Neuroscience & Biobehavioral Reviews.

[5]  S. Elledge,et al.  Taking the brakes off telomerase , 2015, eLife.

[6]  T. Vulliamy,et al.  Triallelic and epigenetic-like inheritance in human disorders of telomerase. , 2015, Blood.

[7]  F. Kronenberg,et al.  Association of relative telomere length with progression of chronic kidney disease in two cohorts: effect modification by smoking and diabetes , 2015, Scientific Reports.

[8]  S. Gregorich,et al.  Leukocyte Telomere Length and Mortality in the National Health and Nutrition Examination Survey, 1999–2002 , 2015, Epidemiology.

[9]  Pui-Yan Kwok,et al.  Automated Assay of Telomere Length Measurement and Informatics for 100,000 Subjects in the Genetic Epidemiology Research on Adult Health and Aging (GERA) Cohort , 2015, Genetics.

[10]  Line Rode,et al.  Peripheral blood leukocyte telomere length and mortality among 64,637 individuals from the general population. , 2015, Journal of the National Cancer Institute.

[11]  S. E. Stanley,et al.  Telomere dysfunction causes alveolar stem cell failure , 2015, Proceedings of the National Academy of Sciences.

[12]  J. Malouff,et al.  THE ASSOCIATION BETWEEN DEPRESSION AND LEUKOCYTE TELOMERE LENGTH: A META‐ANALYSIS , 2015, Depression and anxiety.

[13]  C. Dalgård,et al.  The heritability of leucocyte telomere length dynamics , 2015, Journal of Medical Genetics.

[14]  Param Priya Singh,et al.  A Platform for Rapid Exploration of Aging and Diseases in a Naturally Short-Lived Vertebrate , 2015, Cell.

[15]  E. Blackburn,et al.  Early Telomerase Inactivation Accelerates Aging Independently of Telomere Length , 2015, Cell.

[16]  Joshua D. Podlevsky,et al.  Telomerase mutations in smokers with severe emphysema. , 2015, The Journal of clinical investigation.

[17]  Natalie L. Colich,et al.  Telomere length and cortisol reactivity in children of depressed mothers , 2014, Molecular Psychiatry.

[18]  E. Epel,et al.  Determinants of telomere attrition over one year in healthy older women: Stress and health behaviors matter , 2014, Molecular Psychiatry.

[19]  J. Gu,et al.  Depressive Symptoms and Short Telomere Length Are Associated with Increased Mortality in Bladder Cancer Patients , 2014, Cancer Epidemiology, Biomarkers & Prevention.

[20]  J. Campisi,et al.  Stress and Aging , 2014, Experimental Gerontology.

[21]  C. Fegan,et al.  Telomere dysfunction accurately predicts clinical outcome in chronic lymphocytic leukaemia, even in patients with early stage disease , 2014, British journal of haematology.

[22]  T. Illig,et al.  Glucose substitution prolongs maintenance of energy homeostasis and lifespan of telomere dysfunctional mice , 2014, Nature Communications.

[23]  Stephen Kaptoge,et al.  Leucocyte telomere length and risk of cardiovascular disease: systematic review and meta-analysis , 2014, BMJ : British Medical Journal.

[24]  E. Gilson,et al.  Transcriptional outcome of telomere signalling , 2014, Nature Reviews Genetics.

[25]  Xiuhai Ji,et al.  Clinical Interventions in Aging Dovepress Association between Previously Identified Loci Affecting Telomere Length and Coronary Heart Disease (chd) in Han Chinese Population , 2022 .

[26]  O. Rennert,et al.  Telomerase Protects Werner Syndrome Lineage-Specific Stem Cells from Premature Aging , 2014, Stem cell reports.

[27]  C. Lengacher,et al.  Influence of Mindfulness-Based Stress Reduction (MBSR) on Telomerase Activity in Women With Breast Cancer (BC) , 2014, Biological research for nursing.

[28]  E. Rietzschel,et al.  A non-genetic, epigenetic-like mechanism of telomere length inheritance? , 2013, European Journal of Human Genetics.

[29]  S. Humphries,et al.  Association of TERC and OBFC1 Haplotypes with Mean Leukocyte Telomere Length and Risk for Coronary Heart Disease , 2013, PloS one.

[30]  H. Ding,et al.  Association between Telomere Length and Type 2 Diabetes Mellitus: A Meta-Analysis , 2013, PloS one.

[31]  E. Epel,et al.  Longer leukocyte telomere length in Costa Rica's Nicoya Peninsula: A population-based study , 2013, Experimental Gerontology.

[32]  M. Cayuela,et al.  Premature aging in telomerase-deficient zebrafish , 2013, Disease Models & Mechanisms.

[33]  Susan M. Chang,et al.  Genetic variants in telomerase-related genes are associated with an older age at diagnosis in glioma patients: evidence for distinct pathways of gliomagenesis. , 2013, Neuro-oncology.

[34]  Anthony J. Cesare,et al.  The telomere deprotection response is functionally distinct from the genomic DNA damage response. , 2013, Molecular cell.

[35]  A. Protopopov,et al.  Role of Telomere Dysfunction in Cardiac Failure in Duchenne Muscular Dystrophy , 2013, Nature Cell Biology.

[36]  P. O’Reilly,et al.  Identification of seven loci affecting mean telomere length and their association with disease , 2013, Nature Genetics.

[37]  M. Armanios Telomeres and age-related disease: how telomere biology informs clinical paradigms. , 2013, The Journal of clinical investigation.

[38]  D. Schadendorf,et al.  TERT Promoter Mutations in Familial and Sporadic Melanoma , 2013, Science.

[39]  E. Epel,et al.  Association between telomere length and experimentally induced upper respiratory viral infection in healthy adults. , 2013, JAMA.

[40]  C. Aiken,et al.  Poor maternal nutrition followed by accelerated postnatal growth leads to alterations in DNA damage and repair, oxidative and nitrosative stress, and oxidative defense capacity in rat heart , 2013, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[41]  H. Kao,et al.  Telomeres and Early-Life Stress: An Overview , 2013, Biological Psychiatry.

[42]  E. Blackburn,et al.  The telomere syndromes , 2012, Nature Reviews Genetics.

[43]  T. de Lange,et al.  Removal of Shelterin Reveals the Telomere End-Protection Problem , 2012, Science.

[44]  E. Epel,et al.  Telomeres and lifestyle factors: roles in cellular aging. , 2012, Mutation research.

[45]  D. Hellhammer,et al.  Stress exposure in intrauterine life is associated with shorter telomere length in young adulthood , 2011, Proceedings of the National Academy of Sciences.

[46]  F. Kronenberg,et al.  Fifteen-year follow-up of association between telomere length and incident cancer and cancer mortality. , 2011, JAMA.

[47]  Q. Wei,et al.  Shortened Telomere Length Is Associated with Increased Risk of Cancer: A Meta-Analysis , 2011, PloS one.

[48]  R. Pfeiffer,et al.  The Association of Telomere Length and Cancer: a Meta-analysis , 2011, Cancer Epidemiology, Biomarkers & Prevention.

[49]  S. Shete,et al.  A Genome-Wide Association Study Identifies a Locus on Chromosome 14q21 as a Predictor of Leukocyte Telomere Length and as a Marker of Susceptibility for Bladder Cancer , 2011, Cancer Prevention Research.

[50]  P. Berggren,et al.  Short Telomeres Compromise β-Cell Signaling and Survival , 2011, PloS one.

[51]  L. Chin,et al.  Telomere dysfunction induces metabolic and mitochondrial compromise , 2011, Nature.

[52]  I. Dokal,et al.  Advances in the understanding of dyskeratosis congenita , 2009, British journal of haematology.

[53]  Wilhelm Palm,et al.  How shelterin protects mammalian telomeres. , 2008, Annual review of genetics.

[54]  R. Effros,et al.  Reduced telomerase activity in human T lymphocytes exposed to cortisol , 2008, Brain, Behavior, and Immunity.

[55]  G. Mcclearn,et al.  Telomere length predicts survival independent of genetic influences , 2007, Aging cell.

[56]  A. Jauch,et al.  Telomere dysfunction as a cause of genomic instability in Werner syndrome , 2007, Proceedings of the National Academy of Sciences.

[57]  E. Blackburn,et al.  Telomeres and telomerase: the path from maize, Tetrahymena and yeast to human cancer and aging , 2006, Nature Medicine.

[58]  J. Hodgkin,et al.  trt-1 Is the Caenorhabditis elegans Catalytic Subunit of Telomerase , 2006, PLoS genetics.

[59]  E. Furth,et al.  Telomere Shortening Exposes Functions for the Mouse Werner and Bloom Syndrome Genes , 2004, Molecular and Cellular Biology.

[60]  R. DePinho,et al.  Essential role of limiting telomeres in the pathogenesis of Werner syndrome , 2004, Nature Genetics.

[61]  T. Vulliamy,et al.  The RNA component of telomerase is mutated in autosomal dominant dyskeratosis congenita , 2001, Nature.

[62]  S. Petersen,et al.  Preferential accumulation of single-stranded regions in telomeres of human fibroblasts. , 1998, Experimental cell research.

[63]  María A Blasco,et al.  Telomere Shortening and Tumor Formation by Mouse Cells Lacking Telomerase RNA , 1997, Cell.

[64]  H. Biessmann,et al.  The unusual telomeres of Drosophila. , 1995, Trends in genetics : TIG.