EVALUATING MEASURES OF HEMATOLOGY AND BLOOD-CHEMISTRY IN MALE RHESUS-MONKEYS AS BIOMARKERS OF AGING
EVALUATING MEASURES OF HEMATOLOGY AND BLOOD-CHEMISTRY IN MALE RHESUS-MONKEYS AS BIOMARKERS OF AGING
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DOI：
10.1016/0531-5565(94)90048-5
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发表时间：
1994-03-01
影响因子：
3.9
通讯作者：
INGRAM, DK
中科院分区：
文献类型：
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作者：
NAKAMURA, E;LANE, MA;INGRAM, DK
可靠和有效的衰老生物标志物可以为检查可能影响衰老过程速度的干预措施的有效性提供有价值的工具。然而，识别衰老生物标志物的标准化方法尚未开发出来。目前的分析集中在对雄性恒河猴(N=29)进行的为期5年的纵向研究中获得的血液学和血液化学变量，这些研究采用了一种已知的饮食限制制度，该制度可以延缓实验室啮齿动物的衰老过程并延长寿命(对照组饮食摄入量的70%)。在目前的分析中，确定衰老候选生物标志物的主要筛选标准是与实际年龄(CA)的横断面和纵向相关性以及个体差异的稳定性。从一组血液化学测试中确定了六个潜在变量：1)血清谷草转氨酶；2)碱性磷酸酶；3)总蛋白；4)球蛋白；5)尿素氮/肌酐比率；以及6)磷酸盐。当提交主成分分析时，这些变量被加载到占总方差50%以上的单个分量上，以表明它们之间的显著协方差。通过应用第一主成分的因子得分系数，推导出估计每只猴子的生物学年龄得分(BAS)的方程。对照和限制饮食的猴子的BAS的比较显示，目前没有统计学上的显著差异；然而，与实验组相比，对照组的BAS回归到CA的斜率似乎更陡峭。因此，尽管候选生物标记物的有效性有待于进一步的证据，但作为对过去方法的改进，提出了一种可以识别更多衰老生物标记物的策略。
Reliable and valid biomarkers of aging can provide valuable tools for examining the effectiveness of interventions that may influence the rate of aging processes. However, a standardized method for identifying biomarkers of aging has yet to be developed. The current analysis focused on hematology and blood chemistry variables obtained from a 5-year longitudinal study of male rhesus monkeys (N = 29) on a diet restriction regime known to retard aging processes and extend lifespan in laboratory rodents (70% of the diet intake of controls). For the current analysis, the major screening criteria for identifying candidate biomarkers of aging were cross-sectional and longitudinal correlation with chronological age (CA) and stability of individual differences. Six potential variables from the battery of blood chemistry tests were identified: 1) serum glutamic oxalacetic transaminase; 2) alkaline phosphatase; 3) total protein; 4) globulin; 5) blood urea nitrogen to creatinine ratio; and 6) phosphates. When submitted to principle component analysis, these variables loaded onto a single component that accounted for over 50% of the total variance to indicate marked covariance among them. By applying the factor score coefficients from the first principle component, an equation was derived for estimating a biological age score (BAS) for each individual monkey. A comparison of BAS between control and diet-restricted monkeys revealed no statistically significant difference at present; however, the slope of the regression of BAS onto CA appeared steeper for the control group compared to the experimental group. Thus, while demonstration of the validity of the candidate biomarkers awaits further evidence, a strategy by which additional biomarkers of aging can be identified is proposed as an improvement over past approaches.