title: Telomere Length and the Cancer-Atherosclerosis Trade-Off.
abstract: Modern humans, the longest-living terrestrial mammals, display short telomeres and repressed telomerase activity in somatic tissues compared with most short-living small mammals. The dual trait of short telomeres and repressed telomerase might render humans relatively resistant to cancer compared with short-living small mammals. However, the trade-off for cancer resistance is ostensibly increased age-related degenerative diseases, principally in the form of atherosclerosis. In this communication, we discuss (a) the genetics of human telomere length, a highly heritable complex trait that is influenced by genetic ancestry, sex, and paternal age at conception, (b) how cancer might have played a role in the evolution of telomere biology across mammals, (c) evidence that in modern humans telomere length is a determinant (rather than only a biomarker) of cancer and atherosclerosis, and (d) the potential influence of relatively recent evolutionary forces in fashioning the variation in telomere length across and within populations, and their likely lasting impact on major diseases in humans. Finally, we propose venues for future research on human telomere genetics in the context of its potential role in shaping the modern human lifespan.
authors.affiliation: The Center of Human Development and Aging, New Jersey Medical School, Rutgers, Newark, New Jersey, United States of America.
authors.forename: Rivka C
authors.initials: RC
authors.lastname: Stone
authors.affiliation: The Center of Human Development and Aging, New Jersey Medical School, Rutgers, Newark, New Jersey, United States of America.
authors.forename: Kent
authors.initials: K
authors.lastname: Horvath
authors.affiliation: Epidemiology Unit, Hebrew University-Hadassah School of Public Health and Community Medicine, Jerusalem, Israel.
authors.forename: Jeremy D
authors.initials: JD
authors.lastname: Kark
authors.affiliation: Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York, United States of America.|New York State Psychiatric Institute, New York, New York, United States of America.
authors.forename: Ezra
authors.initials: E
authors.lastname: Susser
authors.affiliation: Department of Genetics, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.|Department of Biology, School of Arts and Sciences, University of Pennsylvania, Philadelphia, Pennsylvania, United States of America.
authors.forename: Sarah A
authors.initials: SA
authors.lastname: Tishkoff
authors.affiliation: The Center of Human Development and Aging, New Jersey Medical School, Rutgers, Newark, New Jersey, United States of America.
authors.forename: Abraham
authors.initials: A
authors.lastname: Aviv
mesh_terms: D000375:Aging / Q000235:genetics; D050197:Atherosclerosis / Q000235:genetics* / Q000473:pathology; D006801:Humans; D008136:Longevity / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology; D016615:Telomere / Q000235:genetics*; D059505:Telomere Homeostasis / Q000235:genetics*; D059506:Telomere Shortening