Mouse Research Bolsters Controversial Theory of Aging
Aging is a process we humans tend to fight every step of the way. The results of a mouse study underscore the potential of antioxidants as a tool in that battle: animals genetically modified to produce more antioxidant enzymes lived longer than control animals did. They also exhibited fewer age-related health problems overall.
The free radical theory of aging posits that substances with unpaired electrons attack the body's molecules and cause the functional decline of organs over time. Thus, antioxidants, which neutralize free radicals, should slow this deterioration. But animal models of aging designed to test the hypothesis have so far shown contradictory results.
In the new work, Peter S. Rabinovitch of the University of Washington and his colleagues engineered mice to produce higher-than-normal amounts of the enzyme catalase. Within cells, catalase removes hydrogen peroxide, a waste product of metabolism that could otherwise lead to damaging oxygen free radicals. In a paper published online this week by Science, the team reports that animals with higher levels of catalase in their mitochondria--the cell's energy-producing organelles--lived 20 percent longer on average than control animals did. What is more, mice in this so-called MCAT group had healthier heart tissue than normal mice and showed fewer mutations in their mitochondrial DNA. "This study is very supportive of the free-radical theory of aging," Rabinovitch says. "It shows the significance of free radicals, and of reactive oxygen species in particular, in the aging process."
Animals that overexpressed catalase in other parts of the cell, such as the nucleus, also exhibited longer life spans than their normal counterparts did, but the gains were modest. As such, the scientists note, the results reinforce the importance of mitochondria as a supplier of free radicals. The researchers have no plans to modify humans to increase protein expression, but they point out that future drug development could focus on protecting the body from free radicals. --Sarah Graham
2005年5月6日，来自美国华盛顿大学的Peter S. Rabinovitch及其同事在《科学》杂志的网站上发表的一篇论文指出，线粒体（细胞的能量制造器官）内有较多过氧化氢酶的动物比一般动物的寿命长20%。过氧化氢作为新陈代谢的废物会破坏氧自由基（oxygen free radical），而过氧化氢酶则能排除细胞内的过氧化氢。研究人员使试验老鼠产生的过氧化氢酶数量多于正常标准，发现这不仅能延长老鼠的寿命，而且其心脏组织也比普通老鼠健康，线粒体DNA的突变也比较少。Rabinovitch指出，这项研究能有效地支持衰老的自由基学说（free-radical theory of aging），同时表明了自由基、活性氧粒子在老化过程中的重要性。
衰老的自由基学说指出，自由基中的不配对电子攻击人体内其他物质的分子，从而进行配对，引起器官功能衰退。这样，用来抑制自由基活动的抗氧化剂，将会减缓细胞的衰老。很多用来验证这一学说的动物实验产生的结果并不是统一的，而这一研究结果有力地支持了衰老的自由基学说。
动物细胞的其他部分（如核子）拥有过度表达过氧化氢酶的话，其寿命也会比相应较长。同样，科学家指出这项研究结果加强了线粒体作为自由基供应者的重要性。研究人员未曾打算增加人类体内的蛋白质表达，但他们指出未来的药物开发可以集中于保护人体免受自由基的侵害。
