生物医学研究中常见的非人灵长类物种的寿命和健康寿命比较

Hillary F Huber, Hannah C Ainsworth, Ellen E Quillen, Adam Salmon, Corinna Ross, Adinda D Azhar, Karen Bales, Michele A Basso, Kristine Coleman, Ricki Colman, Huda S Darusman, Bill Hopkins, Charlotte E Hotchkiss, Matthew J Jorgensen, Kylie Kavanagh, Cun Li, Julie A Mattison, Peter W Nathanielsz, Suryo Saputro, Diana G Scorpio, Paul-Michael Sosa, Eric J Vallender, Yaomin Wang, Caroline J Zeiss, Carol A Shively, Laura A Cox
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引用次数: 0

摘要

生物医学研究中使用的非人灵长类动物(NHP)亟需生成年龄和性别特异性生存曲线,以一致地描述其计时衰老的特征。准确测量计时衰老对于推断物种内和物种间非人灵长类寿命差异的遗传、人口和生理变量至关重要。了解 NHP 的寿命与公共卫生息息相关,因为揭示与转化相关的 NHP 物种在整个生命过程中的人口、分子和临床健康基础对于研究人类衰老具有根本性的重要意义。15 家主要研究机构提供了超过 110,000 只圈养个体 NHP 的数据,在 12 个转化衰老模型中使用统一方法生成了性别特异性 Kaplan-Meier 生存曲线:Callithrix jacchus (common marmoset)、Chlorocebus aethiops sabaeus (vervet/African green)、Macaca fascicularis (cynomolgus macaque)、M. fuscata (Japanese macaque)、M. mulatta (rhesus macaque)、M. nemestrina (pigtail macaque)、M.黑猩猩)、Papio hamadryas spp.(狒狒)、Plecturocebus cupreus(铜金丝猴)、Saguinus oedipus(棉顶狨)和 Saimiri spp.(松鼠猴)。在采用严格的纳入标准后,主要分析结果基于存活至成年期并死于自然/健康相关原因的 12,269 只国家保护动物。我们还对 32,616 只死于任何原因的 NHP 进行了二次分析。在主要分析中,我们报告了存活率第 25、50、75 和 85 百分位数的年龄、最大观察年龄、存活率以及通过量子回归模型和 Kolmogorov-Smirnov 检验所捕捉到的性别差异。我们的研究结果表明,在猫科动物(非洲和亚洲灵长类动物)中,尤其是猕猴,雄性存活率较低,而在板手类(中美洲和南美洲灵长类动物)中则没有这种现象。许多物种的中位寿命都低于以前的报道。一个重要的考虑因素是,这些分析可能比寿命更能反映健康状况。用于研究的圈养 NHP 通常在其自然寿命结束前出于人道福利原因被实施安乐死,通常是在确诊其首次患上需要长期治疗且生活质量下降的重大疾病(如子宫内膜异位症、癌症、骨关节炎)之后。在一些物种中,慢性疾病的典型发病年龄与中位寿命估计值相近,这也证明了这些数据能够捕捉到健康寿命。该数据资源代表了迄今为止对 12 个生物医学相关物种的性别特异性寿命和死亡年龄分布的最全面描述。这些结果澄清了非家养动物年龄之间的关系,并将为老龄化研究界提供宝贵的资源,改善人类-非家养动物的年龄对应关系,使研究人员了解分配到研究中的非家养动物的预期存活率,为未来的研究提供比较指标,并有助于我们了解物种内部和物种之间寿命差异的驱动因素。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Comparative lifespan and healthspan of nonhuman primate species common to biomedical research
There is a critical need to generate age- and sex-specific survival curves to characterize chronological aging consistently across nonhuman primates (NHP) used in biomedical research. Accurate measures of chronological aging are essential for inferences into genetic, demographic, and physiological variables driving differences in NHP lifespan within and between species. Understanding NHP lifespans is relevant to public health because unraveling the demographic, molecular, and clinical bases of health across the life course in translationally relevant NHP species is fundamentally important to the study of human aging. Data from more than 110,000 captive individual NHP were contributed by 15 major research institutions to generate sex-specific Kaplan-Meier survival curves using uniform methods in 12 translational aging models: Callithrix jacchus (common marmoset), Chlorocebus aethiops sabaeus (vervet/African green), Macaca fascicularis (cynomolgus macaque), M. fuscata (Japanese macaque), M. mulatta (rhesus macaque), M. nemestrina (pigtail macaque), M. radiata (bonnet macaque), Pan troglodytes spp. (chimpanzee), Papio hamadryas spp. (baboon), Plecturocebus cupreus (coppery titi monkey), Saguinus oedipus (cotton-top tamarin), and Saimiri spp. (squirrel monkey). After employing strict inclusion criteria, primary analysis results are based on 12,269 NHP that survived to adulthood and died of natural/health-related causes. A secondary analysis was completed for 32,616 NHP that died of any cause. For the primary analyses, we report ages of 25th, 50th, 75th, and 85th percentiles of survival, maximum observed ages, rates of survivorship, and sex-based differences captured by quantile regression models and Kolmogorov-Smirnov tests. Our findings show a pattern of reduced male survival among catarrhines (African and Asian primates), especially macaques, but not platyrrhines (Central and South American primates). For many species, median lifespans were lower than previously reported. An important consideration is that these analyses may offer a better reflection of healthspan than lifespan. Captive NHP used in research are typically euthanized for humane welfare reasons before their natural end of life, often after diagnosis of their first major disease requiring long-term treatment with reduced quality of life (e.g., endometriosis, cancer, osteoarthritis). Supporting the idea that these data are capturing healthspan, for several species typical age at onset of chronic disease is similar to the median lifespan estimates. This data resource represents the most comprehensive characterization of sex-specific lifespan and age-at-death distributions for 12 biomedically relevant species, to date. The results clarify the relationships among NHP ages and will provide a valuable resource for the aging research community, improving human-NHP age equivalencies, informing investigators of the expected survival rates of NHP assigned to studies, providing a metric for comparisons in future studies, and contributing to our understanding of the factors that drive lifespan differences within and among species.
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