Instituto de Investigação em Ciências da Vida e Saúde, Escola de Ciências da Saúde, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Proc Natl Acad Sci U S A. 2010 Aug 24;107(34):15123-8. doi: 10.1073/pnas.1004432107. Epub 2010 Aug 9.
The free radical theory of aging posits oxidative damage to macromolecules as a primary determinant of lifespan. Recent studies challenge this theory by demonstrating that in some cases, longevity is enhanced by inactivation of oxidative stress defenses or is correlated with increased, rather than decreased reactive oxygen species and oxidative damage. Here we show that, in Saccharomyces cerevisiae, caloric restriction or inactivation of catalases extends chronological lifespan by inducing elevated levels of the reactive oxygen species hydrogen peroxide, which activate superoxide dismutases that inhibit the accumulation of superoxide anions. Increased hydrogen peroxide in catalase-deficient cells extends chronological lifespan despite parallel increases in oxidative damage. These findings establish a role for hormesis effects of hydrogen peroxide in promoting longevity that have broad implications for understanding aging and age-related diseases.
衰老的自由基理论认为，大分子的氧化损伤是决定寿命的主要因素。最近的研究挑战了这一理论，表明在某些情况下，通过抑制氧化应激防御的失活或与增加而不是减少活性氧物种和氧化损伤相关联，可以延长寿命。在这里，我们表明，在酿酒酵母中，通过诱导活性氧物种过氧化氢水平升高，热量限制或过氧化氢酶的失活可延长酵母的程序性寿命，从而激活超氧化物歧化酶，抑制超氧阴离子的积累。尽管过氧化氢酶缺陷细胞中的氧化损伤平行增加，但过氧化氢的增加仍延长了程序性寿命。这些发现确立了过氧化氢的应激效应在促进长寿中的作用，这对理解衰老和与年龄相关的疾病具有广泛的意义。
