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Epigenetic alterati...
Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice
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- Xie, Kan (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Ryan, Devon P. (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Pearson, Brandon L. (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Henzel, Kristin S. (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Neff, Frauke (author)
- Institute of Pathology, Helmholtz Zentrum München, German Research Center for Environmental Health, 85764 Neuherberg, Germany;;German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
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- Vidal, Ramon O. (author)
- Computational Systems Biology Lab, German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany;
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- Hennion, Magali (author)
- Computational Systems Biology Lab, German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany;
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- Lehmann, Isabelle (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Schleif, Melvin (author)
- Selective Vulnerability of Neurodegenerative Diseases Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Schröder, Susanne (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Adler, Thure (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;;Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany;
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- Rathkolb, Birgit (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;;Chair of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, 81377 Munich, Germany;
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- Rozman, Jan (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;;German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;
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- Schütz, Anna-Lena (author)
- Computational Systems Biology Lab, German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany;
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- Prehn, Cornelia (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
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- Mickael, Michel E. (author)
- Computational Systems Biology Lab, German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany;
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- Weiergräber, Marco (author)
- Research Group Experimental Neuropsychopharmacology, Federal Institute for Drugs and Medical Devices, 53175 Bonn, Germany;
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- Adamski, Jerzy (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;;Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85350 Freising-Weihenstephan, Germany;
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- Busch, Dirk H. (author)
- Institute for Medical Microbiology, Immunology and Hygiene, Technische Universität München, 81675 Munich, Germany;
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- Ehninger, Gerhard (author)
- Department of Internal Medicine I, University Hospital Carl Gustav Carus, Technical University Dresden, 01307 Dresden, Germany;
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- Matynia, Anna (author)
- Jules Stein Eye Institute, University of California, Los Angeles, CA 90095;
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- Jackson, Walker S. (author)
- Selective Vulnerability of Neurodegenerative Diseases Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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- Wolf, Eckhard (author)
- Chair of Molecular Animal Breeding and Biotechnology, Gene Center, Ludwig-Maximilians-Universität München, 81377 Munich, Germany;
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- Fuchs, Helmut (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
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- Gailus-Durner, Valerie (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;
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- Bonn, Stefan (author)
- Computational Systems Biology Lab, German Center for Neurodegenerative Diseases (DZNE), 37077 Göttingen, Germany;;German Center for Neurodegenerative Diseases (DZNE), 72076 Tübingen, Germany;;Center for Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, 20251 Hamburg, Germany
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- Hrabě de Angelis, Martin (author)
- German Mouse Clinic, Institute of Experimental Genetics, Helmholtz Zentrum München, 85764 Neuherberg, Germany;;German Center for Diabetes Research (DZD), 85764 München-Neuherberg, Germany;;Chair of Experimental Genetics, Center of Life and Food Sciences Weihenstephan, Technische Universität München, 85350 Freising-Weihenstephan, Germany;
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- Ehninger, Dan (author)
- Molecular and Cellular Cognition Lab, German Center for Neurodegenerative Diseases (DZNE), 53127 Bonn, Germany;
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(creator_code:org_t)
- 2018-02-21
- 2018
- English.
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In: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences (PNAS). - 0027-8424 .- 1091-6490. ; 115:10, s. E2348-E2357
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https://liu.diva-por... (primary) (Raw object)
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https://www.pnas.org...
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https://doi.org/10.1...
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Abstract
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- Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice.
Keyword
- aging; epigenetics; intergenerational inheritance; mTOR; sperm
Publication and Content Type
- ref (subject category)
- art (subject category)
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Xie, Kan
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Ryan, Devon P.
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Pearson, Brandon ...
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Henzel, Kristin ...
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Neff, Frauke
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Vidal, Ramon O.
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Hennion, Magali
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Lehmann, Isabell ...
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Schleif, Melvin
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Schröder, Susann ...
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Adler, Thure
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Rathkolb, Birgit
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Rozman, Jan
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Schütz, Anna-Len ...
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Prehn, Cornelia
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Mickael, Michel ...
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Weiergräber, Mar ...
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Adamski, Jerzy
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Busch, Dirk H.
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Ehninger, Gerhar ...
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Matynia, Anna
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Jackson, Walker ...
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Wolf, Eckhard
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Fuchs, Helmut
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Gailus-Durner, V ...
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Bonn, Stefan
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Hrabě de Angelis ...
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Ehninger, Dan
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Linköping University