Comment on "HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction"

Department of Biochemistry , University of Washington Seattle, Seattle, Washington, United States
Science (Impact Factor: 33.61). 07/2006; 312(5778):1312; author reply 1312. DOI: 10.1126/science.1124608
Source: PubMed


Calorie restriction (CR) increases life span in yeast independently of Sir2. Lamming et al. (Reports, 16 September 2005, p. 1861) recently proposed that Sir2-independent life-span extension by CR is mediated by the
Sir2 paralogs Hst1 and Hst2. Contradictory to this, we find that CR greatly increases life span in cells lacking Sir2, Hst1,
and Hst2, which suggests that CR is not mediated by Sir2, Hst2, or Hst1.

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Available from: Matt Kaeberlein
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    • "This result is similar to those observed in most higher eukaryotes in that starvation does not extend lifespan, and high food intake results in high reproduction and shorter lifespan [23]. The difference between our results and those observations that severe DR (0.05%) extended lifespan could arise from different culture conditions [24], [25], [26]. "
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    ABSTRACT: The traditional view on dietary restriction has been challenged with regard to extending lifespan of the fruit fly Drosophila melanogaster. This is because studies have shown that changing the balance of dietary components without reduction of dietary intake can increase lifespan, suggesting that nutrient composition other than dietary restriction play a pivotal role in regulation of longevity. However, this opinion has not been reflected in yeast aging studies. Inspired by this new finding, response surface methodology was applied to evaluate the relationships between nutrients (glucose, amino acids and yeast nitrogen base) and lifespan as well as biomass production in four Saccharomyces cerevisiae strains (wild-type BY4742, sch9Δ, tor1Δ, and sir2Δ mutants) using a high throughput screening assay. Our results indicate that lifespan extension by a typical dietary restriction regime was dependent on the nutrients in media and that nutrient composition was a key determinant for yeast longevity. Four different yeast strains were cultured in various media, which showed similar response surface trends in biomass production and viability at day two but greatly different trends in lifespan. The pH of aging media was dependent on glucose concentration and had no apparent correlation with lifespan under conditions where amino acids and YNB were varied widely, and simply buffering the pH of media could extend lifespan significantly. Furthermore, the results showed that strain sch9Δ was more responsive in nutrient-sensing than the other three strains, suggesting that Sch9 (serine-threonine kinase pathway) was a major nutrient-sensing factor that regulates cell growth, cell size, metabolism, stress resistance and longevity. Overall, our findings support the notion that nutrient composition might be a more effective way than simple dietary restriction to optimize lifespan and biomass production from yeast to other organisms.
    Full-text · Article · May 2013 · PLoS ONE
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    • "Also, deletion of AFG3 results in slow growth and respiratory deficiency in the W303AR strain background, but fails to extend RLS in this strain (Fig. S4d). This is consistent with our prior data that DR also fails to extend RLS in this strain background (Kaeberlein et al., 2006). A second alternative explanation is the possibility that loss of AFG3 induces yeast cells to lose their mitochondrial DNA (become rho 0 ), which can reduce growth rate and has previously been shown to extend RLS in some strain backgrounds (Kirchman et al., 1999). "
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    ABSTRACT: While environmental stress likely plays a significant role in promoting aging, the relationship remains poorly understood. In order to characterize this interaction in a more comprehensive manner, we examined the stress response profiles for 46 long-lived yeast mutant strains across four different stress conditions (oxidative, ER, DNA damage, and thermal), grouping genes based on their associated stress response profiles. Unexpectedly, cells lacking the mitochondrial AAA protease gene AFG3 clustered strongly with long-lived strains lacking cytosolic ribosomal proteins of the large subunit. Similar to these ribosomal protein mutants, afg3∆ cells show reduced cytoplasmic mRNA translation, enhanced resistance to tunicamycin that is independent of the ER unfolded protein response, and Sir2-independent but Gcn4-dependent life span extension. These data demonstrate an unexpected link between a mitochondrial protease, cytoplasmic mRNA translation, and aging. © 2012 The Authors Aging Cell © 2012 Blackwell Publishing Ltd/Anatomical Society of Great Britain and Ireland.
    Full-text · Article · Nov 2012 · Aging cell
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    • "SIRT2 is the mammalian ortholog of yeast HST2 (Perrod et al., 2001). Similar to SIR2, HST2 is upregulated by CR as well as oxidative stress and extends lifespan by a SIR2-independent mechanism (Lamming et al., 2005; Zhu et al., 2012). In future experiments, it will be important to determine if mice overexpressing SIRT2 mice show an altered lifespan. "
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    ABSTRACT: Sirtuin proteins are conserved regulators of aging that have recently emerged as important modifiers of several diseases which commonly occur later in life such as cancer, diabetes, cardiovascular, and neurodegenerative diseases. In mammals, there are seven sirtuins (SIRT1-7), which display diversity in subcellular localization and function. SIRT1 has received much of attention due to its possible impact on longevity, while important biological and therapeutic roles of other sirtuins have been underestimated and just recently recognized. Here we focus on SIRT2, a member of the sirtuin family, and discuss its role in cellular and tissue-specific functions. This review summarizes the main scientific advances on SIRT2 protein biology and explores its potential as a therapeutic target for treatment of age-related disorders.
    Full-text · Article · May 2012 · Frontiers in Pharmacology
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