我们为什么会衰老？是什么让我们当中的一些人比其他人活得更长？几十年来，研究人员一直在试图通过阐明衰老的分子病因来解答这些问题。最为流行的理论之一就是随着时间的推移，活性氧积累可能是导致衰老的潜在罪魁祸首。活性氧能够导致诸如脂质、蛋白和核酸之类的细胞组分发生损伤，从而造成氧化应激(oxidative stress)。然而，氧化应激在衰老中所起的作用仍然充满争议，而用来对抗氧化应激的抗氧化剂疗效也是存在争议。
根据2012年7月19日在线发表在Molecular Cell期刊上的一篇论文，来自美国密歇根大学分子生物学家Ursula Jakob和她的同事们在线虫中测量活性氧并鉴定出遭受氧化应激影响的过程。
他们利用秀丽隐杆线虫(C. Elegans)作为研究对象，令人吃惊地发现这种线虫在远未到老年时就被迫处理高水平活性氧。在发育早期，线虫体内堆积这高水平的活性氧。一旦这些线虫达到成年时，活性氧水平下降，而且只在生命的较后阶段才急剧上升。令人关注的是，能够存活非常长时间的线虫突变体要比寿命短的线虫突变体更好地处理活性氧和更早地从中恢复。这些发现提示着处理较早期的活性氧并从中恢复过来的能力可能能够预测动物寿命。
如今，这项研究仍在继续开展，以便发现这种较早期的活性氧积累背后的机制，以及是否可能通过操纵生命早期的活性氧水平来潜在性地影响有机体的寿命。(生物谷：Bioon.com)
本文编译自Does presence of oxidants early in life help determine life span?
doi: 10.1016/j.molcel.2012.06.016
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Quantitative In Vivo Redox Sensors Uncover Oxidative Stress as an Early Event in Life
Daniela Knoefler1, 5, Maike Thamsen1, 5, Martin Koniczek2, 4, Nicholas J. Niemuth3, Ann-Kristin Diederich1, Ursula Jakob
Obstacles in elucidating the role of oxidative stress in aging include difficulties in (1) tracking in vivo oxidants, in (2) identifying affected proteins, and in (3) correlating changes in oxidant levels with life span. Here, we used quantitative redox proteomics to determine the onset and the cellular targets of oxidative stress during Caenorhabditis elegans’ life span. In parallel, we used genetically encoded sensor proteins to determine peroxide levels in live animals in real time. We discovered that C. elegans encounters significant levels of oxidants as early as during larval development. Oxidant levels drop rapidly as animals mature, and reducing conditions prevail throughout the reproductive age, after which age-accompanied protein oxidation sets in. Long-lived daf-2 mutants transition faster to reducing conditions, whereas short-lived daf-16 mutants retain higher oxidant levels throughout their mature life. These results suggest that animals with improved capacity to recover from early oxidative stress have significant advantages later in life.
