Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity

Kyle M Schachtschneider; Lawrence B Schook; Jennifer J Meudt; Dhanansayan Shanmuganayagam; Joseph A Zoller; Amin Haghani; Caesar Z Li; Joshua Zhang; Andrew Yang; Ken Raj; Steve Horvath

doi:10.1007/s11357-021-00439-6

Epigenetic clock and DNA methylation analysis of porcine models of aging and obesity

Geroscience. 2021 Oct;43(5):2467-2483. doi: 10.1007/s11357-021-00439-6. Epub 2021 Sep 15.

Authors

Kyle M Schachtschneider^{1

2

3}, Lawrence B Schook^{1

4}, Jennifer J Meudt⁵, Dhanansayan Shanmuganayagam^{5

6}, Joseph A Zoller⁷, Amin Haghani⁷, Caesar Z Li⁷, Joshua Zhang⁸, Andrew Yang⁷, Ken Raj⁹, Steve Horvath^{10

11}

Affiliations

¹ Department of Radiology, University of Illinois At Chicago, Chicago, IL, USA.
² Department of Biochemistry and Molecular Genetics, University of Illinois At Chicago, Chicago, IL, USA.
³ National Center for Supercomputing Applications, University of Illinois At Urbana-Champaign, Urban, IL, USA.
⁴ Department of Animal Sciences, University of Illinois At Urbana-Champaign, Urbana, IL, USA.
⁵ Biomedical & Genomic Research Group, Department of Animal and Dairy Sciences, University of Wisconsin - Madison, Madison, WI, USA.
⁶ Department of Surgery, University of Wisconsin School of Medicine and Public Health, Madison, WI, USA.
⁷ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Gonda Building, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA.
⁹ Radiation Effects Department, Centre for Radiation, Chemical and Environmental Hazards, Public Health England, Chilton, Didcot, UK.
¹⁰ Department of Biostatistics, Fielding School of Public Health, University of California, Los Angeles, Los Angeles, CA, USA. shorvath@mednet.ucla.edu.
¹¹ Department of Human Genetics, David Geffen School of Medicine, University of California, Los Angeles, Gonda Building, 695 Charles Young Drive South, Los Angeles, CA, 90095, USA. shorvath@mednet.ucla.edu.

Abstract

DNA-methylation profiles have been used successfully to develop highly accurate biomarkers of age, epigenetic clocks, for many species. Using a custom methylation array, we generated DNA methylation data from n = 238 porcine tissues including blood, bladder, frontal cortex, kidney, liver, and lung, from domestic pigs (Sus scrofa domesticus) and minipigs (Wisconsin Miniature Swine™). Samples used in this study originated from Large White X Landrace crossbred pigs, Large White X Minnesota minipig crossbred pigs, and Wisconsin Miniature Swine™. We present 4 epigenetic clocks for pigs that are distinguished by their compatibility with tissue type (pan-tissue and blood clock) and species (pig and human). Two dual-species human-pig pan-tissue clocks accurately measure chronological age and relative age, respectively. We also characterized CpGs that differ between minipigs and domestic pigs. Strikingly, several genes implicated by our epigenetic studies of minipig status overlap with genes (ADCY3, TFAP2B, SKOR1, and GPR61) implicated by genetic studies of body mass index in humans. In addition, CpGs with different levels of methylation between the two pig breeds were identified proximal to genes involved in blood LDL levels and cholesterol synthesis, of particular interest given the minipig's increased susceptibility to cardiovascular disease compared to domestic pigs. Thus, breed-specific differences of domestic and minipigs may potentially help to identify biological mechanisms underlying weight gain and aging-associated diseases. Our porcine clocks are expected to be useful for elucidating the role of epigenetics in aging and obesity, and the testing of anti-aging interventions.

Keywords: Aging; DNA methylation; Development; Epigenetic clock; Minipigs; Pig; Porcine.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Aging / genetics
Animals
DNA Methylation*
Epigenesis, Genetic*
Obesity
Swine / genetics
Swine, Miniature