Human telomere biology: pitfalls of moving from the laboratory to epidemiology.

Remarkable progress has been made during the last 2 decades in understanding telomere biology at the molecular and cellular levels. Clinical epidemiology research of human telomeres, in contrast, is a discipline just coming into its own. The most important observation in studying human telomere biology is that telomere length is highly variable among humans. Here we explain some of the reasons for this variability and propose several principles that should be considered in conducting epidemiological telomere research. Ignoring these principles could lead to misleading conclusions.

[1]  R. Kronmal,et al.  Leukocyte telomere length and cardiovascular disease in the cardiovascular health study. , 2006, American journal of epidemiology.

[2]  T. Spector,et al.  The effects of social status on biological aging as measured by white‐blood‐cell telomere length , 2006, Aging cell.

[3]  D. Levy,et al.  Insulin resistance, oxidative stress, hypertension, and leukocyte telomere length in men from the Framingham Heart Study , 2006, Aging cell.

[4]  T. Spector,et al.  Mapping genetic loci that determine leukocyte telomere length in a large sample of unselected female sibling pairs. , 2006, American journal of human genetics.

[5]  G. Hughes,et al.  Atherogenesis in rheumatology , 2006, Lupus.

[6]  J. Vaupel,et al.  No Association Between Telomere Length and Survival Among the Elderly and Oldest Old , 2006, Epidemiology.

[7]  T. Spector,et al.  Menopause modifies the association of leukocyte telomere length with insulin resistance and inflammation. , 2006, The Journal of clinical endocrinology and metabolism.

[8]  R. Westendorp,et al.  Telomere length in white blood cells is not associated with morbidity or mortality in the oldest old: a population‐based study , 2005, Aging cell.

[9]  A. Aviv,et al.  Rise in Insulin Resistance Is Associated With Escalated Telomere Attrition , 2005, Circulation.

[10]  S. Chanock,et al.  Mutations in TERT, the gene for telomerase reverse transcriptase, in aplastic anemia. , 2005, The New England journal of medicine.

[11]  K. Riabowol,et al.  Paternal age is positively linked to telomere length of children , 2005, Aging cell.

[12]  F. Miedema,et al.  Significance of senescence for virus-specific memory T cell responses: rapid ageing during chronic stimulation of the immune system. , 2005, Immunology letters.

[13]  A. Tzankov,et al.  Age‐related loss of naïve T cells and dysregulation of T‐cell/B‐cell interactions in human lymph nodes , 2005, Immunology.

[14]  A. Aviv.  Telomeres and human aging: facts and fibs. , 2004, Science of aging knowledge environment : SAGE KE.

[15]  E. Epel,et al.  Accelerated telomere shortening in response to life stress. , 2004, Proceedings of the National Academy of Sciences of the United States of America.

[16]  Rita B. Effros,et al.  Genetic Manipulation of Telomerase in HIV-Specific CD8+ T Cells: Enhanced Antiviral Functions Accompany the Increased Proliferative Potential and Telomere Length Stabilization1 , 2004, The Journal of Immunology.

[17]  J. O. D. Buijs,et al.  Mathematical modeling confirms the length-dependency of telomere shortening , 2004, Mechanisms of Ageing and Development.

[18]  J. Staessen,et al.  Telomere length and possible link to X chromosome , 2004, The Lancet.

[19]  R. Effros.  Impact of the Hayflick Limit on T cell responses to infection: lessons from aging and HIV disease , 2004, Mechanisms of Ageing and Development.

[20]  A. Aviv,et al.  Short Telomeres Are Associated With Increased Carotid Atherosclerosis in Hypertensive Subjects , 2004, Hypertension.

[21]  S. Schönland,et al.  Premature telomeric loss in rheumatoid arthritis is genetically determined and involves both myeloid and lymphoid cell lineages , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[22]  J. Shay,et al.  Developmental differences in the immortalization of lung fibroblasts by telomerase , 2003, Aging cell.

[23]  P. Lansdorp,et al.  Telomere length measurements in leukocyte subsets by automated multicolor flow‐FISH , 2003, Cytometry. Part A : the journal of the International Society for Analytical Cytology.

[24]  S. Saito,et al.  Telomerase activity and telomere length of peripheral blood mononuclear cells in SLE patients , 2003, Lupus.

[25]  E. Mariani,et al.  Different rates of telomere shortening and telomerase activity reduction in CD8 T and CD16 NK lymphocytes with ageing , 2003, Experimental Gerontology.

[26]  J. Ambrose,et al.  Reactive Oxygen Species Are Involved in Smoking-Induced Dysfunction of Nitric Oxide Biosynthesis and Upregulation of Endothelial Nitric Oxide Synthase: An In Vitro Demonstration in Human Coronary Artery Endothelial Cells , 2003, Circulation.

[27]  N. Samani,et al.  White Cell Telomere Length and Risk of Premature Myocardial Infarction , 2003, Arteriosclerosis, thrombosis, and vascular biology.

[28]  J. Cummings,et al.  Telomere shortening in T cells correlates with Alzheimer’s disease status , 2003, Neurobiology of Aging.

[29]  R. Cawthon,et al.  Association between telomere length in blood and mortality in people aged 60 years or older , 2003, The Lancet.

[30]  P. Lansdorp,et al.  Telomere maintenance in human B lymphocytes , 2002, British journal of haematology.

[31]  Alan S. Perelson,et al.  In vivo dynamics of T cell activation, proliferation, and death in HIV-1 infection: Why are CD4+ but not CD8+ T cells depleted? , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[32]  J. Skurnick,et al.  Telomere Length in the Newborn , 2002, Pediatric Research.

[33]  R. Cawthon.  Telomere measurement by quantitative PCR. , 2002, Nucleic acids research.

[34]  N. Weng.  Interplay between telomere length and telomerase in human leukocyte differentiation and aging , 2001, Journal of leukocyte biology.

[35]  T. Fischer,et al.  Particulate and vapor phase constituents of cigarette mainstream smoke and risk of myocardial infarction. , 2001, Atherosclerosis.

[36]  N. Samani,et al.  Telomere shortening in atherosclerosis , 2001, The Lancet.

[37]  J. Skurnick,et al.  Telomere Length as an Indicator of Biological Aging: The Gender Effect and Relation With Pulse Pressure and Pulse Wave Velocity , 2001, Hypertension.

[38]  E. Blackburn,et al.  Telomere states and cell fates , 2000, Nature.

[39]  A. Risch,et al.  Short Telomeres in Patients with Vascular Dementia: An Indicator of Low Antioxidative Capacity and a Possible Risk Factor? , 2000, Laboratory Investigation.

[40]  R. Effros,et al.  Ageing of lymphocytes and lymphocytes in the aged. , 2000, Immunology today.

[41]  R. Hodes,et al.  Lineage-Specific Telomere Shortening and Unaltered Capacity for Telomerase Expression in Human T and B Lymphocytes with Age , 2000, The Journal of Immunology.

[42]  J. Skurnick,et al.  Telomere length inversely correlates with pulse pressure and is highly familial. , 2000, Hypertension.

[43]  Nathalie Rufer,et al.  Telomere Fluorescence Measurements in Granulocytes and T Lymphocyte Subsets Point to a High Turnover of Hematopoietic Stem Cells and Memory T Cells in Early Childhood , 1999, The Journal of experimental medicine.

[44]  W. Telford,et al.  Postthymic development of CD28-CD8+ T cell subset: age-associated expansion and shift from memory to naive phenotype. , 1999, Journal of immunology.

[45]  G. Roos,et al.  Telomere analysis by fluorescence in situ hybridization and flow cytometry. , 1998, Nucleic acids research.

[46]  J. Haines,et al.  Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium. , 1997, JAMA.

[47]  H. Ostrer,et al.  Shortened telomeres in clonally expanded CD28-CD8+ T cells imply a replicative history that is distinct from their CD28+CD8+ counterparts. , 1996, Journal of immunology.

[48]  H. Tanke,et al.  Heterogeneity in telomere length of human chromosomes. , 1996, Human molecular genetics.

[49]  B L Levine,et al.  Human naive and memory T lymphocytes differ in telomeric length and replicative potential. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[50]  D I Boomsma,et al.  Genetic determination of telomere size in humans: a twin study of three age groups. , 1994, American journal of human genetics.

[51]  T. Reichert,et al.  Age-related changes in human blood lymphocyte subpopulations. II. Varying kinetics of percentage and absolute count measurements. , 1994, Clinical immunology and immunopathology.

[52]  W. Pryor,et al.  Oxidants in Cigarette Smoke Radicals, Hydrogen Peroxide, Peroxynitrate, and Peroxynitrite a , 1993, Annals of the New York Academy of Sciences.

[53]  C B Harley,et al.  Loss of telomeric DNA during aging of normal and trisomy 21 human lymphocytes. , 1993, American journal of human genetics.

[54]  V. Deneys,et al.  Age-related changes in human blood lymphocyte subpopulations. , 1992, The Journal of pediatrics.

[55]  C. Harley,et al.  Telomeres shorten during ageing of human fibroblasts , 1990, Nature.

[56]  R. Collins,et al.  Blood pressure, stroke, and coronary heart disease Part 1, prolonged differences in blood pressure: prospective observational studies corrected for the regression dilution bias , 1990, The Lancet.

[57]  William A. Pryor,et al.  The Tar Radical ( s ) in Cigarette Smoke : ESR Studies , 2006 .

[58]  N. Amso,et al.  Telomere instability in the male germline. , 2006, Human molecular genetics.

[59]  G. Moneta.  Short Telomeres Are Associated With Increased Carotid Atherosclerosis in Hypertensive SubjectsBenetos A, Gardner JP, Zureik M, et al (Centre d'Investigations Préventives et Cliniques, Paris; Med School of Nancy, France; INSERM U258, Villejuif, France; et al) Hypertension 43:182–185, 2004§ , 2006 .

[60]  Andrea H. Mason,et al.  Mapping of a major locus that determines telomere length in humans. , 2005, American journal of human genetics.

[61]  Lieu Tl,et al.  Obesity, cigarette smoking, and telomere length in women , 2005 .

[62]  T. von Zglinicki.  Replicative senescence and the art of counting. , 2003, Experimental gerontology.

[63]  S. Thompson,et al.  Correcting for regression dilution bias: comparison of methods for a single predictor variable , 2000 .

[64]  P. Lansdorp,et al.  Telomere length dynamics in human lymphocyte subpopulations measured by flow cytometry , 1998, Nature Biotechnology.

[65]  G. Casella,et al.  Statistical Inference , 2003, Encyclopedia of Social Network Analysis and Mining.