Increased aerobic metabolism is essential for the beneficial effects of caloric restriction on yeast life span

Abstract

Calorie restriction is a dietary regimen capable of extending life span in a variety of multicellular organisms. A yeast model of calorie restriction has been developed in which limiting the concentration of glucose in the growth media of Saccharomyces cerevisiae leads to enhanced replicative and chronological longevity. Since S. cerevisiae are Crabtree-positive cells that present repression of aerobic catabolism when grown in high glucose concentrations, we investigated if this phenomenon participates in life span regulation in yeast. S. cerevisiae only exhibited an increase in chronological life span when incubated in limited concentrations of glucose. Limitation of galactose, raffinose or glycerol plus ethanol as substrates did not enhance life span. Furthermore, in Kluyveromyces lactis, a Crabtree-negative yeast, glucose limitation did not promote an enhancement of respiratory capacity nor a decrease in reactive oxygen species formation, as is characteristic of conditions of caloric restriction in S. cerevisiae. In addition, K. lactis did not present an increase in longevity when incubated in lower glucose concentrations. Altogether, our results indicate that release from repression of aerobic catabolism is essential for the beneficial effects of glucose limitation in the yeast calorie restriction model. Potential parallels between these changes in yeast and hormonal regulation of respiratory rates in animals are discussed.

Caloric restriction and redox state: Does this diet increase or decrease oxidant production?

“…S. cerevisiae is a Crabtree-positive yeast that, when cultured in high glucose, presents predominantly fermentative metabolism and undergoes respiratory de-repression when cultured under CR, an effect central toward lifespan expansion. 84 As a result of lower fermentative activity, CR cells present pronounced increases in pH compared to control cells (up to 3 pH points, Tahara and Kowaltowski, unpublished results), which can, alone, explain large increases in DCF fluorescence in this model even in the absence of changes in redox state.…”

“…29 The oxidized product of DHR is positively charged, and used as a mitochondrial membrane potential marker. 85 Since CR in S. cerevisiae significantly increases mitochondrial activity, 25,26,84 the accumulation of this dye in CR cells may be attributable to enhancement of mitochondrial density and membrane potentials, and not to increased H 2 O 2 . In addition, DHR is not a selective probe for H 2 O 2 , 80 as claimed by the authors.…”

Oxidative Stress: Noxious but Also Vital

“…Mitochondria, as the major site of ROS production, have been associated with aging process [55,56]. Moreover, studies with caloric restriction in yeast and mammals have shown that the mitochondria, ROS, and RNS have an important role in the aging process [34,[56][57][58][59][60][61]. …”

Caracterização da tolerância ao estresse oxidativo, capacidade de remoção de proteínas oxidadas e a expectativa de vida de linhagens da levedura S. cerevisiae com mutações sítio-específicas na subunidade α5 do proteassomo 20S: implicações na prevenção de agregação.

“…Para analisar a sensibilidade das linhagens selvagem e mutantes C221 e C76 a diferentes tratamentos com peróxido de hidrogênio utilizamos o método adaptado a partir de OLIVEIRA et al, 2008;TAHARA et al, 2007).…”

“…Identificamos também uma proteína down-regulated relacionada indiretamente com a longevidade, a FKBP (FK506-binding protein 1). As FKBPs são proteína que interagem com drogas imunossupressoras como a Rapamicina formando complexos capazes de inibir a via de TOR (BROWN et al, 1994;HARRISON et al, 2009 (BALCH et al, 2008;HIPP et al, 2014;KNOWLES et al, 2014;OLZSCHA et al, 2011). No entanto, estudos com C. elegans conduzidos por Walther et al, (2015) mostraram um aumento na formação de agregados associados a pequenas proteínas de choque térmico (small-heat shock proteins) na linhagem mutante de maior durabilidade (daf-2).…”