, 95447, Bayreuth, Germany.
School of Life Sciences, Center for Evolution and Medicine, School for Human Evolution and Social Change, Arizona State University, Tempe, AZ, USA.
Geroscience. 2023 Apr;45(2):627-643. doi: 10.1007/s11357-022-00653-w. Epub 2022 Sep 6.
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.
虽然小体型和杂种优势的寿命优势已被反复记录,但遗传多样性对犬种的影响证据尚存在争议。我们假设,这可能是由于可用的特定犬种寿命估计中存在强烈的右删失偏差,其中来自尚未完全死亡的出生队列的早逝狗不成比例地被抽样,尤其是在人口快速增长的犬种中。我们利用来自大型公共数据库的主人报告的寿命和死因数据,根据超过 40,000 只狗的数据,根据 118 个犬种量化了体型和遗传多样性(杂合度)对死亡率模式的影响。在通过仅包括已完成的出生队列来记录并从特定犬种的寿命估计中消除右删失偏差后,我们表明小体型和遗传多样性都与各犬种的平均寿命显著增加有关。为了更好地理解这些模式的潜在机制,我们随后研究了犬类的两个主要死亡原因——老年和癌症的累积病理生理学。老年寿命以及老年死亡率的百分比随着体型的增加而减少,随着遗传多样性的增加而增加。死于癌症的狗的寿命也遵循相同的模式,但虽然大体型显著增加了癌症的比例死亡率,但我们无法检测到遗传多样性增加与癌症死亡率降低的显著信号。我们的发现表明,杂交计划将有益于犬种的健康和长寿。它们还强调了兽医流行病学以及将犬作为人类老年学转化模型开发所需的高质量死亡率数据的必要性。