Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome

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

Research output: Contribution to journalArticle

Abstract

All mammals progress through similar physiological stages throughout life, from early development to puberty, aging, and death. Yet, the extent to which this conserved physiology reflects underlying genomic events is unclear. Here, we map the common methylation changes experienced by mammalian genomes as they age, focusing on comparison of humans with dogs, an emerging model of aging. Using oligo-capture sequencing, we characterize methylomes of 104 Labrador retrievers spanning a 16-year age range, achieving >150× coverage within mammalian syntenic blocks. Comparison with human methylomes reveals a nonlinear relationship that translates dog-to-human years and aligns the timing of major physiological milestones between the two species, with extension to mice. Conserved changes center on developmental gene networks, which are sufficient to translate age and the effects of anti-aging interventions across multiple mammals. These results establish methylation not only as a diagnostic age readout but also as a cross-species translator of physiological aging milestones. Wang et al. create an oligo-capture system to characterize the canine DNA methylome, targeting syntenic regions of the genome conserved across all mammals. Cross-species comparisons reveal a nonlinear epigenetic signature that aligns the progression of life events in dogs, humans, and mice. This conserved signature occurs primarily in modules of developmental genes, leading the team to create a conserved epigenetic clock model of aging that can be trained and operated across different species.

Original languageEnglish (US)
Pages (from-to)176-185.e6
JournalCell Systems
Volume11
Issue number2
DOIs
StatePublished - Aug 26 2020

Keywords

  • aging
  • canine
  • dog
  • epigenetic aging
  • epigenetic clock
  • epigenetics
  • epigenome
  • evolution
  • methylation
  • methylome

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Histology
  • Cell Biology

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  • Cite this

    Wang, T., Ma, J., Hogan, A. N., Fong, S., Licon, K., Tsui, B., Kreisberg, J. F., Adams, P. D., Carvunis, A. R., Bannasch, D. L., Ostrander, E. A., & Ideker, T. (2020). Quantitative Translation of Dog-to-Human Aging by Conserved Remodeling of the DNA Methylome. Cell Systems, 11(2), 176-185.e6. https://doi.org/10.1016/j.cels.2020.06.006