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Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks

View ORCID ProfileTina Wang, View ORCID ProfileJianzhu Ma, Andrew N. Hogan, View ORCID ProfileSamson Fong, Katherine Licon, View ORCID ProfileBrian Tsui, View ORCID ProfileJason F. Kreisberg, Peter D. Adams, View ORCID ProfileAnne-Ruxandra Carvunis, Danika L. Bannasch, Elaine A. Ostrander, View ORCID ProfileTrey Ideker
doi: https://doi.org/10.1101/829192
Tina Wang
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, US
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  • ORCID record for Tina Wang
Jianzhu Ma
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, US
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Andrew N. Hogan
2National Human Genome Research Institute, Bethesda, MD 20892, USA
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Samson Fong
3Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
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Katherine Licon
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, US
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Brian Tsui
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, US
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Jason F. Kreisberg
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, US
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Peter D. Adams
4Sanford Burnham Prebys Medical Discovery Institute, La Jolla, CA 92093, USA
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Anne-Ruxandra Carvunis
5Department of Computational and Systems Biology, Pittsburgh Center for Evolutionary Biology and Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
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Danika L. Bannasch
6Department of Population Health and Reproduction, School of Veterinary Medicine, University of California Davis, Davis, CA, United States of America
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Elaine A. Ostrander
2National Human Genome Research Institute, Bethesda, MD 20892, USA
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Trey Ideker
1Division of Genetics, Department of Medicine, University of California San Diego, La Jolla, CA 92093, US
3Department of Bioengineering, University of California San Diego, La Jolla, CA 92093, USA
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  • For correspondence: tideker@ucsd.edu
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SUMMARY

Mammals progress through similar physiological stages during life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects conserved molecular events is unclear. Here, we map common epigenetic changes experienced by mammalian genomes as they age, focusing on evolutionary comparisons of humans to dogs, an emerging model of aging. Using targeted sequencing, we characterize the methylomes of 104 Labrador retrievers spanning a 16 year age range, achieving >150X coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship which translates dog to human years, aligns the timing of major physiological milestones between the two species, and extends to mice. Conserved changes center on specific developmental gene networks which are sufficient to capture the effects of anti-aging interventions in multiple mammals. These results establish methylation not only as a diagnostic age readout but as a cross-species translator of physiological aging milestones.

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Posted November 04, 2019.
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Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks
Tina Wang, Jianzhu Ma, Andrew N. Hogan, Samson Fong, Katherine Licon, Brian Tsui, Jason F. Kreisberg, Peter D. Adams, Anne-Ruxandra Carvunis, Danika L. Bannasch, Elaine A. Ostrander, Trey Ideker
bioRxiv 829192; doi: https://doi.org/10.1101/829192
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Quantitative translation of dog-to-human aging by conserved remodeling of epigenetic networks
Tina Wang, Jianzhu Ma, Andrew N. Hogan, Samson Fong, Katherine Licon, Brian Tsui, Jason F. Kreisberg, Peter D. Adams, Anne-Ruxandra Carvunis, Danika L. Bannasch, Elaine A. Ostrander, Trey Ideker
bioRxiv 829192; doi: https://doi.org/10.1101/829192

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