Journal
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
Volume 107, Issue 34, Pages 15123-15128Publisher
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1004432107
Keywords
aging; hydrogen peroxide; hormesis; antioxidant enzymes; oxidative damage
Categories
Funding
- Fundacao para a Ciencia e Tecnologia, Portugal [PTDC/AGR-ALI/71460/2006]
- Fundacao para a Ciencia e Tecnologia [SFRH/BD/32464/2006, SFRH/BD/33125/2007, SFRH/BD/41674/2007]
- National Cancer Institute Cancer Center [P30 CA016056]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/32464/2006, SFRH/BD/33125/2007, SFRH/BD/41674/2007, PTDC/AGR-ALI/71460/2006] Funding Source: FCT
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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.
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