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Why study aging in dogs? The Dog Aging Project: • Genetic variation for aging and age-related disease A Multi-Omic National Study of Healthy • Live in our own environment Aging in Companion Dogs • Much shorter lifespan than humans Daniel Promislow1, Kate Creevy2, Jessica Hoffman3, Josh Akey4, and Elinor Karlsson5 • Spectrum of diseases similar to those found in humans 1University of Washington, Seattle, WA, • Highly sophisticated health care system 2Texas A&M University, College Station, TX, 3Department of Biology, Birmingham, AL, • Owners are passionate about pet health 4Princeton University, Princeton, NJ 5Broad Institute & U Mass Med School, Cambridge, MA • Potential for long-term longitudinal studies www.dogagingproject.com @DPromislow [email protected] @dogagingproject
The Dog Aging Project Team What have we learned about dog aging Scientific Leadership Group Administration Daniel Promislow (PI) Charlie Lieu (Director of Program Operations) Matt Kaeberlein (Co-Director) Ellen Cravens (Lead Admin Assistant) • Breeds vary in duration of life, cause of death Kate Creevy (Chief Veterinary Officer) Julia Lawrence (Grant Management) • PMID 21352376;PMID 23535614 Josh Akey (Genetics) Erica Jonlin (Compliance) Elhanan Borenstein (Micriobiome) • Similarities and differences in age-related disease in dogs vs. Advisory Kyle Crowder (Environment & Health) Scientific Advisory Board (Chair, Brian Kennedy) humans Matt Dunbar (Demography) Animal Welfare Advisory Board (Chair, Patty • PMID: 29457329 With Kate Creevy Annette Fitzpatrick (Public Health) Olson, DVM) Elinor Karlsson (Genetics) Data and Safety Monitoring Board (TBD) • Comorbidity: Age- and disease-specific Kathleen Kerr (Statistics) • PMC5120387 Jon Levine (Vet Clinical Trials) NIA Jing Ma (Multi-omic Statistics) Felipe Sierra • Sterilized dogs live longer, more likely to die of cancer & autoimmune Sean Mooney (Informatics) Francesca Macchiarini disease Ron Kohanski Audrey Ruple (Vet Epidemiology) • PMC3629191 Carrie Sturts-Dossick (Engineering) Luigi Ferrucci Steve Schwartz (Epidemiology) • Low-dose rapamycin in middle-aged dogs (Phase I) Jon Wakefield (Statistics Genetics) • PMC5411365;PMC5352585 Ben Wilfond (Pediatric Ethics) With Matt Kaeberlein Andrea Wills (Epigenetics) • Good safety profile, some improvement in left ventricular heart function Liz Zampino (Informatics)
Why study The Dog Aging Project (NIA U19)
gGeenonmees ++ Eennvvirioronmnmenet nt aging in dogs? P1. Define “healthy aging” in a dog P2. Genetic determinants of healthy Maddy: 5 years & 10 years aging transcript -ome
P3. Systems biology to study metabol -ome mechanisms by which genotype Aaggee epigen phenotype (metabolome, -ome ATAC-seq epigenome, proteome
microbiome) etc. P4. TRIAD trial (Test of Rapamycin Lily: 8 months & 15 years In Aging Dogs) http://www.amandajones.com/ Aging and agaeg-inreglated disease
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Dog Aging Project Cohorts Outreach (1000’s of Shared Terabytes)
• The Dog Aging Project is an Open Science project Foundation Cohort 10,000 dogs • Partnerships with human studies (DNA, EMRs) • Ancillary studies Vet data, Environmental data, • Citizen geroscience Intervention Cohort Precision Cohort owner-provided data • Educational goals 500 dogs 1200 dogs (+ rapamycin) (+ omics, activity)
DAP Logistics Current status
Public EMR mgmt data • Infrastructure development (Early 2019) Participant info Home DATA Key: data - Website, Data Core - Smart phone app Core
s i - DAP-client, DAP-vet, and client-client communication
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R&R Sample kits ß Data transfer - Choose 10,000 (by breed, sex, age, geography, and SES)
Reference Lab Sample transfer - Sample collection & Projects Vets distribution - Clinical chemistry
1000’s Terabytes A few of our goals
1. Identify disease-specific genes 2. Identify genetic determinants of age-related frailty and survival 3. Genetic signature of ‘canine centenarians’ 4. G E effects on aging and age-related disease. 5. Epigenetic clock as aging biomarker 6. Genetic determinants of –omic variation [email protected] dogagingproject.com
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Mortality and Comorbidity in Dogs
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Sterilization and Cause of Death Immune-mediated *** Neoplastic ***
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