Conservation of physiological dysregulation signatures of aging across primates
Conservation of physiological dysregulation signatures of aging across primates
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DOI：
10.1111/acel.12925
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发表时间：
2019-04-01
期刊：
影响因子：
7.8
通讯作者：
Cohen, Alan A.
中科院分区：
文献类型：
--
作者：
Dansereau, Gabriel;Wey, Tina W.;Cohen, Alan A.
当前衰老生物学的两个主要目标是确定衰老过程的一般机制和解释衰老的物种差异。最近对人类的研究表明，衰老的一个重要驱动因素是失调，即复杂生物网络中稳态的逐渐丧失。然而，这一假设缺乏比较数据，我们不知道失调是否与衰老广泛相关，或者稳态信号的保守程度如何。为了解决这一知识缺口，我们使用来自研究中心的10种非人灵长类动物的异常详细的纵向生物标志物数据和来自两个人类群体的数据来检验以下假设：（a）更大的失调与灵长类动物的衰老相关，（B）表征稳态的生理状态在灵长类动物中保守到与系统发育接近相关的程度。为了评估失调，我们采用了多变量距离测量，从生物标志物组计算，这是与人口老龄化和死亡率。在大多数非人灵长类动物研究中，失调评分与年龄和死亡风险呈正相关，稳态信号在不同物种间显着保守，随着系统发育距离的增加而下降。我们的研究首次广泛证明了多种非人类灵长类动物中与衰老和死亡风险相关的生理失调。我们的研究结果还意味着，紧急信号的稳态进化保守，虽然与物种之间的显着变化，并建议有前途的方向，为未来的比较研究失调和衰老过程。
Two major goals in the current biology of aging are to identify general mechanisms underlying the aging process and to explain species differences in aging. Recent research in humans suggests that one important driver of aging is dysregulation, the progressive loss of homeostasis in complex biological networks. Yet, there is a lack of comparative data for this hypothesis, and we do not know whether dysregulation is widely associated with aging or how well signals of homeostasis are conserved. To address this knowledge gap, we use unusually detailed longitudinal biomarker data from 10 species of nonhuman primates housed in research centers and data from two human populations to test the hypotheses that (a) greater dysregulation is associated with aging across primates and (b) physiological states characterizing homeostasis are conserved across primates to degrees associated with phylogenetic proximity. To evaluate dysregulation, we employed a multivariate distance measure, calculated from sets of biomarkers, that is associated with aging and mortality in human populations. Dysregulation scores positively correlated with age and risk of mortality in most nonhuman primates studied, and signals of homeostatic state were significantly conserved across species, declining with phylogenetic distance. Our study provides the first broad demonstration of physiological dysregulation associated with aging and mortality risk in multiple nonhuman primates. Our results also imply that emergent signals of homeostasis are evolutionarily conserved, although with notable variation among species, and suggest promising directions for future comparative studies on dysregulation and the aging process.