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,，來(lái)自美國(guó)華盛頓大學(xué)的Peter S. Rabinovitch及其同事在《科學(xué)》雜志的網(wǎng)站上發(fā)表的一篇論文指出，線粒體（細(xì)胞的能量制造器官）內(nèi)有較多過(guò)氧化氫酶的動(dòng)物比一般動(dòng)物的壽命長(zhǎng)20%,。過(guò)氧化氫作為新陳代謝的廢物會(huì)破壞氧自由基（oxygen free radical）,，而過(guò)氧化氫酶則能排除細(xì)胞內(nèi)的過(guò)氧化氫,。研究人員使試驗(yàn)老鼠產(chǎn)生的過(guò)氧化氫酶數(shù)量多于正常標(biāo)準(zhǔn),，發(fā)現(xiàn)這不僅能延長(zhǎng)老鼠的壽命，而且其心臟組織也比普通老鼠健康,，線粒體DNA的突變也比較少,。Rabinovitch指出，這項(xiàng)研究能有效地支持衰老的自由基學(xué)說(shuō)（free-radical theory of aging）,，同時(shí)表明了自由基,、活性氧粒子在老化過(guò)程中的重要性。

    衰老的自由基學(xué)說(shuō)指出,，自由基中的不配對(duì)電子攻擊人體內(nèi)其他物質(zhì)的分子,，從而進(jìn)行配對(duì)，引起器官功能衰退,。這樣,，用來(lái)抑制自由基活動(dòng)的抗氧化劑，將會(huì)減緩細(xì)胞的衰老,。很多用來(lái)驗(yàn)證這一學(xué)說(shuō)的動(dòng)物實(shí)驗(yàn)產(chǎn)生的結(jié)果并不是統(tǒng)一的,，而這一研究結(jié)果有力地支持了衰老的自由基學(xué)說(shuō)。

    動(dòng)物細(xì)胞的其他部分（如核子）擁有過(guò)度表達(dá)過(guò)氧化氫酶的話,，其壽命也會(huì)比相應(yīng)較長(zhǎng),。同樣，科學(xué)家指出這項(xiàng)研究結(jié)果加強(qiáng)了線粒體作為自由基供應(yīng)者的重要性,。研究人員未曾打算增加人類體內(nèi)的蛋白質(zhì)表達(dá),，但他們指出未來(lái)的藥物開(kāi)發(fā)可以集中于保護(hù)人體免受自由基的侵害。