Department of Cell Biology, University of Calabria, Rende, Italy.
PLoS One. 2011;6(12):e29650. doi: 10.1371/journal.pone.0029650. Epub 2011 Dec 27.
In humans Uncoupling Proteins (UCPs) are a group of five mitochondrial inner membrane transporters with variable tissue expression, which seem to function as regulators of energy homeostasis and antioxidants. In particular, these proteins uncouple respiration from ATP production, allowing stored energy to be released as heat. Data from experimental models have previously suggested that UCPs may play an important role on aging rate and lifespan. We analyzed the genetic variability of human UCPs in cohorts of subjects ranging between 64 and 105 years of age (for a total of 598 subjects), to determine whether specific UCP variability affects human longevity. Indeed, we found that the genetic variability of UCP2, UCP3 and UCP4 do affect the individual's chances of surviving up to a very old age. This confirms the importance of energy storage, energy use and modulation of ROS production in the aging process. In addition, given the different localization of these UCPs (UCP2 is expressed in various tissues including brain, hearth and adipose tissue, while UCP3 is expressed in muscles and Brown Adipose Tissue and UCP4 is expressed in neuronal cells), our results may suggest that the uncoupling process plays an important role in modulating aging especially in muscular and nervous tissues, which are indeed very responsive to metabolic alterations and are very important in estimating health status and survival in the elderly.
在人类中，解偶联蛋白（UCPs）是一组具有不同组织表达的线粒体内膜转运体，它们似乎作为能量平衡和抗氧化剂的调节剂发挥作用。特别是，这些蛋白将呼吸与 ATP 产生解偶联，允许储存的能量以热量的形式释放。来自实验模型的数据先前表明，UCPs 可能在衰老速度和寿命方面发挥重要作用。我们分析了 64 至 105 岁年龄组（总共 598 名受试者）中人类 UCPs 的遗传变异性，以确定特定的 UCP 变异性是否会影响人类的长寿。事实上，我们发现 UCP2、UCP3 和 UCP4 的遗传变异性确实会影响个体活到非常高龄的机会。这证实了能量储存、能量利用和 ROS 产生的调节在衰老过程中的重要性。此外，鉴于这些 UCPs 的不同定位（UCP2 表达在包括大脑、心脏和脂肪组织在内的各种组织中，而 UCP3 则表达在肌肉和棕色脂肪组织中，UCP4 则表达在神经元细胞中），我们的结果可能表明解偶联过程在调节衰老中发挥着重要作用，特别是在肌肉和神经组织中，这些组织对代谢改变非常敏感，对于评估老年人的健康状况和生存至关重要。
