TY - JOUR
T1 - How size and genetic diversity shape lifespan across breeds of purebred dogs
AU - Kraus, Cornelia
AU - Snyder-Mackler, Noah
AU - Promislow, Daniel E.L.
N1 - Funding Information:
NSM and DELP were supported in part by the Dog Aging Project U19 grant AG057377 (PI: Daniel Promislow) from the National Institute on Aging, a part of the National Institutes of Health. We would also like to thank the koiranet team and the Finnish Kennel Club for providing such a valuable resource and making it publicly available. Thanks to Mirka Jantunen and Karina Whittington for breed-specific info. We are grateful for the helpful comments made by the anonymous reviewers on the manuscript.
Funding Information:
NSM and DELP were supported in part by the Dog Aging Project U19 grant AG057377 (PI: Daniel Promislow) from the National Institute on Aging, a part of the National Institutes of Health. We would also like to thank the koiranet team and the Finnish Kennel Club for providing such a valuable resource and making it publicly available. Thanks to Mirka Jantunen and Karina Whittington for breed-specific info. We are grateful for the helpful comments made by the anonymous reviewers on the manuscript.
Publisher Copyright:
© 2022, The Author(s), under exclusive licence to American Aging Association.
PY - 2023/4
Y1 - 2023/4
N2 - While the lifespan advantage of small body size and mixed breed status has been documented repeatedly, evidence for an effect of genetic diversity across dog breeds is equivocal. We hypothesized that this might be due to a strong right-censoring bias in available breed-specific lifespan estimates where early-dying dogs from birth cohorts that have not died off completely at the time of data collection are sampled disproportionately, especially in breeds with rapidly growing populations. We took advantage of data on owner reported lifespan and cause of death from a large public database to quantify the effect of size and genetic diversity (heterozygosity) on mortality patterns across 118 breeds based on more than 40,000 dogs. After documenting and removing the right-censoring bias from the breed-specific lifespan estimates by including only completed birth cohorts in our analyses, we show that small size and genetic diversity are both linked to a significant increase in mean lifespan across breeds. To better understand the proximate mechanisms underlying these patterns, we then investigated two major mortality causes in dogs — the cumulative pathophysiologies of old age and cancer. Old age lifespan, as well as the percentage of old age mortality, decreased with increasing body size and increased with increasing genetic diversity. The lifespan of dogs dying of cancer followed the same patterns, but while large size significantly increased proportional cancer mortality, we could not detect a significant signal for lowered cancer mortality with increasing diversity. Our findings suggest that outcross programs will be beneficial for breed health and longevity. They also emphasize the need for high-quality mortality data for veterinary epidemiology as well as for developing the dog as a translational model for human geroscience.
AB - While the lifespan advantage of small body size and mixed breed status has been documented repeatedly, evidence for an effect of genetic diversity across dog breeds is equivocal. We hypothesized that this might be due to a strong right-censoring bias in available breed-specific lifespan estimates where early-dying dogs from birth cohorts that have not died off completely at the time of data collection are sampled disproportionately, especially in breeds with rapidly growing populations. We took advantage of data on owner reported lifespan and cause of death from a large public database to quantify the effect of size and genetic diversity (heterozygosity) on mortality patterns across 118 breeds based on more than 40,000 dogs. After documenting and removing the right-censoring bias from the breed-specific lifespan estimates by including only completed birth cohorts in our analyses, we show that small size and genetic diversity are both linked to a significant increase in mean lifespan across breeds. To better understand the proximate mechanisms underlying these patterns, we then investigated two major mortality causes in dogs — the cumulative pathophysiologies of old age and cancer. Old age lifespan, as well as the percentage of old age mortality, decreased with increasing body size and increased with increasing genetic diversity. The lifespan of dogs dying of cancer followed the same patterns, but while large size significantly increased proportional cancer mortality, we could not detect a significant signal for lowered cancer mortality with increasing diversity. Our findings suggest that outcross programs will be beneficial for breed health and longevity. They also emphasize the need for high-quality mortality data for veterinary epidemiology as well as for developing the dog as a translational model for human geroscience.
KW - Cancer
KW - Dog breeds
KW - Genetic diversity
KW - Lifespan
KW - Old age
KW - Size
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UR - http://www.scopus.com/inward/citedby.url?scp=85137523869&partnerID=8YFLogxK
U2 - 10.1007/s11357-022-00653-w
DO - 10.1007/s11357-022-00653-w
M3 - Article
C2 - 36066765
AN - SCOPUS:85137523869
SN - 2509-2715
VL - 45
SP - 627
EP - 643
JO - GeroScience
JF - GeroScience
IS - 2
ER -