Caloric restriction or catalase inactivation extends yeast chronological lifespan by inducing H2O2 and superoxide dismutase activity.
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.
Mesquita
Ana
A
Instituto de Investigação em Ciências da Vida e Saúde, Escola de Ciências da Saúde, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal.
Weinberger
Martin
M
Silva
Alexandra
A
Sampaio-Marques
Belém
B
Almeida
Bruno
B
Leão
Cecília
C
Costa
Vítor
V
Rodrigues
Fernando
F
Burhans
William C
WC
Ludovico
Paula
P
D001483:Base Sequence; D002374:Catalase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003470:Culture Media; D017931:DNA Primers / Q000235:genetics; D006861:Hydrogen Peroxide / Q000378:metabolism*; D008954:Models, Biological; D018384:Oxidative Stress; D017382:Reactive Oxygen Species / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000166:cytology / Q000235:genetics / Q000254:growth & development / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000096:biosynthesis*
D003470:Culture Media; D017931:DNA Primers; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D002374:Catalase; D013482:Superoxide Dismutase