Extension of chronological life span in yeast by decreased TOR pathway signaling.

By R. Powers, Matt Kaeberlein, Seth D Caldwell, Brian K. Kennedy, Stanley Fields. Genes & Development, 2006

1,011 citations recorded by the source corpus.

Chronological life span (CLS) in Saccharomyces cerevisiae, defined as the time cells in a stationary phase culture remain viable, has been proposed as a model for the aging of post-mitotic tissues in mammals. We developed a high-throughput assay to determine CLS for approximately 4800 single-gene deletion strains of yeast, and identified long-lived strains carrying mutations in the conserved TOR pathway. TOR signaling regulates multiple cellular processes in response to nutrients, especially amino acids, raising the possibility that decreased TOR signaling mediates life span extension by calorie restriction. In support of this possibility, removal of either asparagine or glutamate from the media significantly increased stationary phase survival. Pharmacological inhibition of TOR signaling by methionine sulfoximine or rapamycin also increased CLS. Decreased TOR activity also promoted increased accumulation of storage carbohydrates and enhanced stress resistance and nuclear relocalization of the stress-related transcription factor Msn2. We propose that up-regulation of a highly conserved response to starvation-induced stress is important for life span extension by decreased TOR signaling in yeast and higher eukaryotes.

Subfields: Aging, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/0bce5ffae7601acbf63bae596dbd6fd7b50618c3

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Citations in the corpus

Nutritional Control of Growth and Development in Yeast (2012, background): “Such mutants also exhibit extended survival in stationary phase (Powers et al. 2006; Boer et al. 2008).”
Rapamycin, but not resveratrol or simvastatin, extends life span of genetically heterogeneous mice. (2011, background): “Involvement of mTOR in regulation of aging was suggested by evidence that impairment of mTOR activity in flies (9), worms (10,11), and yeast (12) could lead to life span extension, and by observations that mTOR function was lower in several mouse models of slow aging, including data on dwarf mice (1”
Target of Rapamycin (TOR) in Nutrient Signaling and Growth Control (2011, background): “A subsequent high-throughput assay involving 4800 viable single-gene yeast mutants further implicated TORC1 in CLS (Powers et al. 2006).”
Induction of autophagy by spermidine promotes longevity (2009, background): “One of these pathways is regulated by Tor kinases, and decreased TORC1 activity can promote longevity of various organism”
Inhibition of mTOR by Rapamycin Abolishes Cognitive Deficits and Reduces Amyloid-β Levels in a Mouse Model of Alzheimer's Disease (2010, background): “Background: Reduced TOR signaling has been shown to significantly increase lifespan in a variety of organisms [1,2,3,4].”
Sirtuins in aging and age-related disease. (2006, background): “A large-scale search for mutants with an extended replicative life span led to the identification of deletion mutants in sch9 and tor1, also implicated in chronological lifespan extension (Fabrizio et al., 2001; Kaeberlein et al., 2005d; Powers et al., 2006).”
With TOR less is more: a key role for the conserved nutrient sensing TOR pathway in aging (2010, neutral): “Inhibition of TOR also extends yeast chronological life span (CLS), which measures the ability of stationary (in the absence of nutrients) cultures to maintain viability over time (Bonawitz et al., 2007; Powers et al., 2006).”
Mechanisms of Life Span Extension by Rapamycin in the Fruit Fly Drosophila melanogaster (2010, background): “, 2007) and chronological (Powers et al., 2006) life span, and a recent study has shown that rapamycin also extends life span in mice when administered late in life (Harrison et al.”
The role of mitochondria in aging. (2013, neutral): “Impaired IIS and inhibition of TOR activity extend life span in worms, flies, and mammals (101, 103, 105–110).”