Role ofRAS2in Recovery from Chronic Stress: Effect on Yeast Life Span

Shama, Silvian; Kirchman, Paul A.; Jiang, James J.; Jazwinski, S. Michal

doi:10.1006/excr.1998.4276

Cited by 45 publications

(39 citation statements)

References 44 publications

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“…RAS2 is a G-protein that functions in sensing the nutritional status of the cell, and directly regulates cell cycle (Jazwinki et al 1993;Austriaco 1996). Recent studies have also demonstrated that RAS2 is involved in the retrograde response (communication between mitochondria and the nucleus) and the ability of cells to mount a successful stress response (Shama et al 1998;Sinclair et al 1998;MacLean et al 2001;Longo and Fabrizio 2002). Interestingly, studies early on documented a role for deletion of RAS2 positively regulating lifespan (Sinclair et al 1998;MacLean et al 2001;Longo and Fabrizio 2002).…”

Section: Chronological Lifespan or Stationary Phasementioning

confidence: 94%

The stationary phase model of aging in yeast for the study of oxidative stress and age-related neurodegeneration

2005

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Understanding the biochemical and genetic alterations that occur during the aging of post-mitotic cells is critical for understanding the etiology of abnormalities observed during the aging of the central nervous system (CNS). While many theories for cellular aging exist, the free radical theory of aging has proved useful in explaining multiple aspects of post-mitotic cell aging, including the aging of neuronal cells. It is well established that Saccharomyces cerevisiae are an invaluable model system for exploring the regulation of aging in actively dividing cells, but increasing evidence suggests that the chronological lifespan or stationary phase model of aging in S. cerevisiae may also be useful for understanding the aging process in post-mitotic cells. Interestingly, the stationary phase model of aging in S. cerevisiae recapitulates many pathological alterations observed during neuronal aging, including evidence for increased oxidative stress and proteasome inhibition. Studies using proteins relevant to multiple neurodegenerative conditions (prion, alpha-synuclein, huntingtin) have demonstrated the utility of S. cerevisiae as a model system for understanding the genetic regulation of protein aggregation and cell death. Taken together, these data highlight the potential importance of using S. cerevisiae as a model system with which to explore the molecular basis for neuronal alterations observed in normal brain aging as well as multiple age-related diseases of the CNS.

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Section: Chronological Lifespan or Stationary Phasementioning

confidence: 94%

The stationary phase model of aging in yeast for the study of oxidative stress and age-related neurodegeneration

2005

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“…The role of metabolism and its control in determining longevity is on a firm footing with the discovery that the retrograde response determines life span. The importance of resistance to heat stress and ultraviolet radiation (UV) has also been well documented 5,16. Genetic stability is also a factor in maintaining yeast life span 17–19…”

Section: Ras2 Functions As a Homeostat In Yeast Agingmentioning

confidence: 99%

“…Because of this activity, this gene tends to decrease survival when yeasts are exposed to a lethal heat shock. On the other hand, RAS2 has a protective effect when yeasts are exposed to chronic bouts of sublethal heat shock, due to its effective downregulation of stress genes and upregulation of growth‐promoting genes 5. RAS2 , along with RAS1 , is required for the increase in life span seen when yeasts are conditioned by a transient, sublethal heat stress 30.…”

Section: Ras2 Functions As a Homeostat In Yeast Agingmentioning

confidence: 99%

Metabolic Control and Gene Dysregulation in Yeast Aging

Jazwinski

2000

Annals of the New York Academy of Sciences

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Life span in the yeast Saccharomyces cerevisiae is usually measured by the number of divisions individual cells complete. Four broad physiologic processes that determine yeast life span have been identified: metabolic control, resistance to stress, chromatin‐dependent gene regulation, and genetic stability. A pathway of interorganelle communication involving mitochondria, the nucleus, and peroxisomes has provided a molecular mechanism of aging based on metabolic control. This pathway functions continuously, rather than as an on‐off switch, in determining life span. The longevity gene RAS2 modulates this pathway. RAS2 also modulates a variety of other cellular processes, including stress responses and chromatin‐dependent gene regulation. An optimal level of Ras2p activity is required for maximum longevity. This may be due to the integration of life maintenance processes by RAS2, which functions as a homeostatic device in yeast longevity. Loss of transcriptional silencing of heterochromatic regions of the genome is a mark of yeast aging. It is now clear that the functional status of chromatin plays an important role in aging. Changes in this functional status result in gene dysregulation, which can be altered by manipulation of the histone deacetylase genes. Silencing of ribosomal DNA appears to be of particular importance. Extrachromosomal ribosomal DNA circles are neither sufficient nor necessary for yeast aging.

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“…RAS2 modulates the response to a variety of stresses (Marchler et al 1993). Its activity is required to resist the life-spanshortening effect of sublethal, chronic heat stress (Shama et al 1998). This gene is required for resistance to ultraviolet radiation (Engelberg et al 1994), and its expression parallels the biphasic profile of ultraviolet radiation resistance during the yeast life span (Kale and Jazwinski 1996).…”

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confidence: 99%

Homologs of the Yeast Longevity Gene LAG1 in Caenorhabditis elegans and Human

Pa²,

Zagulski³

et al. 1998

Genome Res.

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131

146

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LAG1 is a longevity gene, the first such gene to be identified and cloned from the yeast Saccharomyces cerevisiae. A close homolog of this gene, which we call LAC1, has been found in the yeast genome. We have cloned the human homolog ofLAG1 with the ultimate goal of examining its possible function in human aging. In the process, we have also cloned a homolog from the nematode worm Caenorhabditis elegans. Both of these homologs,LAG1Hs and LAG1Ce-1, functionally complemented the lethality of a lag1Δ lac1Δdouble deletion, despite low overall sequence similarity to the yeast proteins. The proteins shared a short sequence, the Lag1 motif, and a similar transmembrane domain profile. Another, more distant human homolog, TRAM, which lacks this motif, did not complement.LAG1Hs also restored the life span of the double deletion, demonstrating that it functions in establishing the longevity phenotype in yeast. LAG1Hs mapped to 19p12, and it was expressed in only three tissues: brain, skeletal muscle, and testis. This gene possesses a trinucleotide (CTG) repeat within exon 1. This and its expression profile raise the possibility that it may be involved in neurodegenerative disease. This possibility suggests at least one way in which LAG1Hs might be involved in human aging.[The sequence data described in this paper have been submitted to GenBank under accession nos. AF105005–AF105009(LAG1Hs) and AF105010 (LAG1Ce-1).]

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Role ofRAS2in Recovery from Chronic Stress: Effect on Yeast Life Span

Cited by 45 publications

References 44 publications

The stationary phase model of aging in yeast for the study of oxidative stress and age-related neurodegeneration

The stationary phase model of aging in yeast for the study of oxidative stress and age-related neurodegeneration

Metabolic Control and Gene Dysregulation in Yeast Aging

Homologs of the Yeast Longevity Gene LAG1 in Caenorhabditis elegans and Human

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