Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients

  title={Regulation of Yeast Replicative Life Span by TOR and Sch9 in Response to Nutrients},
  author={Matt Kaeberlein and R. Wilson Powers and Kristan K. Steffen and Eric A. Westman and Di Hu and Nick Dang and Emily O. Kerr and Kathryn T. Kirkland and Stanley Fields and Brian K. Kennedy},
  pages={1193 - 1196}
Calorie restriction increases life span in many organisms, including the budding yeast Saccharomyces cerevisiae. [] Key Result From a large-scale analysis of 564 single-gene-deletion strains of yeast, we identified 10 gene deletions that increase replicative life span. Six of these correspond to genes encoding components of the nutrient-responsive TOR and Sch9 pathways.

Yeast Life Span Extension by Depletion of 60S Ribosomal Subunits Is Mediated by Gcn4

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

It is proposed 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.

Tor1/Sch9-Regulated Carbon Source Substitution Is as Effective as Calorie Restriction in Life Span Extension

Data is presented suggesting that yeast Tor1 and Sch9 is a central component of a network that controls a common set of genes implicated in a metabolic switch from the TCA cycle and respiration to glycolysis and glycerol biosynthesis.

Reprogramming Cell Survival and Longevity: The Role of Tor, Sch9, Ras, and Sir2

The role of Tor/Sch9, Ras, and Sir2 in reprogramming survival and chronological life span in S. cerevisiae and their potentially conserved role in higher eukaryotes are reviewed.

DNA Replication Stress Is a Determinant of Chronological Lifespan in Budding Yeast

It is shown that in the budding yeast S. cerevisiae, caloric restriction and osmotic stress increase the efficiency with which nutrient-depleted cells establish or maintain a cell cycle arrest in G1, and Ectopic expression of CLN3 encoding a G1 cyclin downregulated during nutrient depletion shortens chronological lifespan.

Life Span Extension by Calorie Restriction Depends on Rim15 and Transcription Factors Downstream of Ras/PKA, Tor, and Sch9

It is demonstrated that the serine/threonine kinase Rim15 is required for yeast chronological life span extension caused by deficiencies in Ras2, Tor1, and Sch9, and by calorie restriction, while the anti-aging effect caused by the inactivation of both pathways is much more potent than that caused by CR.

Caffeine extends yeast lifespan by targeting TORC1

Treatment of yeast cells with the specificTORC1 inhibitor rapamycin or caffeine releases Rim15 from TORC1‐Sch9‐mediated inhibition and consequently increases lifespan, suggesting that caffeine may extend lifespan in other eukaryotes, including man.

Increased Life Span due to Calorie Restriction in Respiratory-Deficient Yeast

It is demonstrated that respiration is not required for the longevity benefits of CR in yeast, and shows that nicotinamide inhibits life span extension by CR through a Sir2-independent mechanism, and suggests that CR acts through a conserved, Sir2 -independent mechanism in both PSY316 and BY4742.

Nutritional Control of Chronological Aging and Heterochromatin in Saccharomyces cerevisiae

Sir2 was involved in a response to nutrient cues including glucose that regulates chronological aging, possibly through Sir2-dependent modification of chromatin or deacetylation of a nonhistone protein.



Requirement of NAD and SIR2 for life-span extension by calorie restriction in Saccharomyces cerevisiae.

These findings suggest that the increased longevity induced by calorie restriction requires the activation of Sir2p by NAD, the oxidized form of nicotinamide adenine dinucleotide.

Sir2-Independent Life Span Extension by Calorie Restriction in Yeast

It is found that combining calorie restriction with either of these genetic interventions dramatically enhances longevity, resulting in the longest-lived yeast strain reported thus far and indicates that Sir2 and calorie restriction act in parallel pathways to promote longevity in yeast and, perhaps, higher eukaryotes.

HST2 Mediates SIR2-Independent Life-Span Extension by Calorie Restriction

It is shown that Sir2-independent life-span extension is mediated by Hst2, a Sir2 homolog that promotes the stability of repetitive ribosomal DNA, the same mechanism by which Sir2 extends life span.

The SIR2/3/4 complex and SIR2 alone promote longevity in Saccharomyces cerevisiae by two different mechanisms.

It is shown that life span regulation by the Sir proteins is independent of their role in nonhomologous end joining, and increasing the gene dosage extends the life span in wild-type cells.

A dynamic transcriptional network communicates growth potential to ribosome synthesis and critical cell size.

It is suggested that nutrient signals set the critical cell-size threshold via Sfp1 and Sch9-mediated control of ribosome biosynthetic rates.