Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians
Edited by Stephen Curtis Stearns, Yale University, New Haven, CT, and accepted by the Editorial Board October 7, 2009 (received for review July 20, 2009)
Abstract
Telomere length in humans is emerging as a biomarker of aging because its shortening is associated with aging-related diseases and early mortality. However, genetic mechanisms responsible for these associations are not known. Here, in a cohort of Ashkenazi Jewish centenarians, their offspring, and offspring-matched controls, we studied the inheritance and maintenance of telomere length and variations in two major genes associated with telomerase enzyme activity, hTERT and hTERC. We demonstrated that centenarians and their offspring maintain longer telomeres compared with controls with advancing age and that longer telomeres are associated with protection from age-related diseases, better cognitive function, and lipid profiles of healthy aging. Sequence analysis of hTERT and hTERC showed overrepresentation of synonymous and intronic mutations among centenarians relative to controls. Moreover, we identified a common hTERT haplotype that is associated with both exceptional longevity and longer telomere length. Thus, variations in human telomerase gene that are associated with better maintenance of telomere length may confer healthy aging and exceptional longevity in humans.
Acknowledgments
We are indebted to all participants and their families for their dedication and enthusiasm to enroll in the longevity study. We are also grateful to the Hebrew Home for the Aging (Riverdale, NY), Kittay House (Bronx, NY), Hebrew Home Hospital (West Hartford, CT), and Jewish Home for the Aged (New Haven, CT), all under the aegis of the association for the Jewish Aging Services (Washington, DC). This work was supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, Ellison Medical Foundation Senior Scholar Award, Glenn Award for Research in Biological Mechanisms of Aging, and theResnick Gerontology Center, and by National Institutes of Health Grants RO1 AG-18728-01A1, RO1 AG024391, PO1 AG027734, PO1 AG17242 and RO1 AG7992, General Clinical Research Center Grant MO1-RR12248, and Diabetes Research and Training Center Grant DK 20541 at the Albert Einstein College of Medicine. Some of the results of this paper were obtained by using the program package S.A.G.E., which is supported by a U.S. Public Health Service Resource Grant (RR03655) from the National Center for Research Resources.
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Information & Authors
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Published in
Proceedings of the National Academy of Sciences
Vol. 107 | No. suppl_1
January 26, 2010
January 26, 2010
PubMed: 19915151
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Submission history
Published online: November 13, 2009
Published in issue: January 26, 2010
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Acknowledgments
We are indebted to all participants and their families for their dedication and enthusiasm to enroll in the longevity study. We are also grateful to the Hebrew Home for the Aging (Riverdale, NY), Kittay House (Bronx, NY), Hebrew Home Hospital (West Hartford, CT), and Jewish Home for the Aged (New Haven, CT), all under the aegis of the association for the Jewish Aging Services (Washington, DC). This work was supported by grants from the Paul Beeson Physician Faculty Scholar in Aging Award, Ellison Medical Foundation Senior Scholar Award, Glenn Award for Research in Biological Mechanisms of Aging, and theResnick Gerontology Center, and by National Institutes of Health Grants RO1 AG-18728-01A1, RO1 AG024391, PO1 AG027734, PO1 AG17242 and RO1 AG7992, General Clinical Research Center Grant MO1-RR12248, and Diabetes Research and Training Center Grant DK 20541 at the Albert Einstein College of Medicine. Some of the results of this paper were obtained by using the program package S.A.G.E., which is supported by a U.S. Public Health Service Resource Grant (RR03655) from the National Center for Research Resources.
Notes
This paper results from the Arthur M. Sackler Colloquium of the National Academy of Sciences, “Evolution in Health and Medicine” held April 2–3, 2009, at the National Academy of Sciences in Washington, DC. The complete program and audio files of most presentations are available on the NAS web site at www.nasonline.org/Sackler_Evolution_Health_Medicine.
This article is a PNAS Direct Submission. S.C.S. is a guest editor invited by the Editorial Board.
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Competing Interests
The authors declare no conflict of interest.
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Genetic variation in human telomerase is associated with telomere length in Ashkenazi centenarians, Proc. Natl. Acad. Sci. U.S.A.
107 (suppl_1) 1710-1717,
https://doi.org/10.1073/pnas.0906191106
(2010).
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