Nakamura E, Lane M A, Roth G S, Cutler R G, Ingram D K
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institute on Aging, National Institutes of Health, Baltimore, Maryland 21224.
Exp Gerontol. 1994 Mar-Apr;29(2):151-77. doi: 10.1016/0531-5565(94)90048-5.
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.
可靠且有效的衰老生物标志物可为检验可能影响衰老进程速率的干预措施的有效性提供有价值的工具。然而，尚未开发出一种标准化的方法来识别衰老生物标志物。当前的分析聚焦于从一项对雄性恒河猴（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，这些猴子采用一种已知可延缓衰老进程并延长实验室啮齿动物寿命（摄入量为对照组的70%）的饮食限制方案。对于当前的分析，识别衰老候选生物标志物的主要筛选标准是与实足年龄（CA）的横断面和纵向相关性以及个体差异的稳定性。从一系列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）血尿素氮与肌酐比值；6）磷酸盐。当进行主成分分析时，这些变量加载到一个占总方差超过50%的单一成分上，表明它们之间存在显著的协方差。通过应用第一个主成分的因子得分系数，推导出一个用于估计每只猴子生物年龄得分（BAS）的方程。对照组和饮食限制组猴子之间的BAS比较目前未显示出统计学上的显著差异；然而，与实验组相比，对照组中BAS对CA的回归斜率似乎更陡。因此，虽然候选生物标志物有效性的证明有待进一步证据，但提出了一种识别更多衰老生物标志物的策略，作为对过去方法的改进。
