我們?yōu)槭裁磿ダ?？是什么讓我們當中的一些人比其他人活得更長,？幾十年來，研究人員一直在試圖通過闡明衰老的分子病因來解答這些問題,。最為流行的理論之一就是隨著時間的推移,，活性氧積累可能是導(dǎo)致衰老的潛在罪魁禍首?；钚匝跄軌?qū)е轮T如脂質(zhì),、蛋白和核酸之類的細胞組分發(fā)生損傷，從而造成氧化應(yīng)激(oxidative stress),。然而,，氧化應(yīng)激在衰老中所起的作用仍然充滿爭議，而用來對抗氧化應(yīng)激的抗氧化劑療效也是存在爭議,。
根據(jù)2012年7月19日在線發(fā)表在Molecular Cell期刊上的一篇論文,，來自美國密歇根大學分子生物學家Ursula Jakob和她的同事們在線蟲中測量活性氧并鑒定出遭受氧化應(yīng)激影響的過程。
他們利用秀麗隱桿線蟲(C. Elegans)作為研究對象,，令人吃驚地發(fā)現(xiàn)這種線蟲在遠未到老年時就被迫處理高水平活性氧,。在發(fā)育早期，線蟲體內(nèi)堆積這高水平的活性氧,。一旦這些線蟲達到成年時,，活性氧水平下降，而且只在生命的較后階段才急劇上升,。令人關(guān)注的是,，能夠存活非常長時間的線蟲突變體要比壽命短的線蟲突變體更好地處理活性氧和更早地從中恢復(fù)。這些發(fā)現(xiàn)提示著處理較早期的活性氧并從中恢復(fù)過來的能力可能能夠預(yù)測動物壽命,。
如今,，這項研究仍在繼續(xù)開展，以便發(fā)現(xiàn)這種較早期的活性氧積累背后的機制,，以及是否可能通過操縱生命早期的活性氧水平來潛在性地影響有機體的壽命,。(生物谷：Bioon.com)
本文編譯自Does presence of oxidants early in life help determine life span?
doi: 10.1016/j.molcel.2012.06.016
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PMID:
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.
