A novel gene, ecl1+, extends the chronological lifespan in fission yeast (original) (raw)
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Genes to Cells, 2012
+ , ecl2 + and ecl3 + genes encode highly homologous small proteins, and their over-expressions confer both H 2 O 2 stress resistance and chronological lifespan extension on Schizosaccharomyces pombe. However, the mechanisms of how these Ecl1 family proteins function have not been elucidated. In this study, we conducted microarray analysis and identified that the expression of genes involved in sexual development and stress responses was affected by the over-expression of Ecl1 family proteins. In agreement with the mRNA expression profile, the cells over-expressing Ecl1 family proteins showed high mating efficiency and resistant phenotype to H 2 O 2. We showed that the H 2 O 2-resistant phenotype depends on catalase Ctt1, and over-expression of ctt1 + does not affect chronological lifespan. Furthermore, we showed that six genes, ste11 + , spk1 + , hsr1 + , rsv2 + , hsp9 + and lsd90 + , whose expressions are increased in cells over-expressing Ecl1 family proteins are involved in chronological lifespan in fission yeast. Among these genes, the induction of ste11 + and hsr1 + was dependent on a transcription factor Prr1, and we showed that the extensions of chronological lifespan by Ecl1 family proteins are remarkably diminished in prr1 deletion mutant. From these results, we propose that Ecl1-family proteins conduct H 2 O 2 stress resistance and chronological lifespan extension in ctt1 +-and prr1 +-dependent manner, respectively.
Regulation of chronological aging in Schizosaccharomyces pombe by the protein kinases Pka1 and Sck2
Aging Cell, 2006
Budding yeast shows a progressive decline in viability after entering stationary phase, a phenomenon known as chronological aging. We show here that the fission yeast Schizosaccharomyces pombe also undergoes chronological aging and that the process is regulated by genes controlling two related nutrient signalling pathways. The first pathway includes the serine/threonine cAMP-activated protein kinase Pka1 and the second pathway comprises the serine/threonine kinase Sck2, a homologue of Saccharomyces cerevisiae SCH9. A double mutant for pka1 and sck2 displayed an additive effect on prolonging the fission yeast lifespan, suggesting that these genes regulate related but independent pathways. These long-lived mutants also accumulated less reactive oxygen species and had a delayed initiation of apoptosis compared with wild-type cells. We also found that strains carrying pka1 deletion but not those with sck2 deletion gained resistance to oxidative stress due to exposure to H2O2 or menadione. On the other hand, the additional increase in lifespan shown by the Δpka1Δsck2 double-mutant strain correlated with an increased resistance to both oxidative stress and heat shock. These results underscore the importance of nutrient signalling pathways and reactive oxygen species on organismal lifespan and establish S. pombe as a new model organism to study the molecular mechanisms underlying aging.
Yeast Chronological Lifespan: Longevity Regulatory Genes and Mechanisms
Cells
S. cerevisiae plays a pivotal role as a model system in understanding the biochemistry and molecular biology of mammals including humans. A considerable portion of our knowledge on the genes and pathways involved in cellular growth, resistance to toxic agents, and death has in fact been generated using this model organism. The yeast chronological lifespan (CLS) is a paradigm to study age-dependent damage and longevity. In combination with powerful genetic screening and high throughput technologies, the CLS has allowed the identification of longevity genes and pathways but has also introduced a unicellular “test tube” model system to identify and study macromolecular and cellular damage leading to diseases. In addition, it has played an important role in studying the nutrients and dietary regimens capable of affecting stress resistance and longevity and allowing the characterization of aging regulatory networks. The parallel description of the pro-aging roles of homologs of RAS, S6 k...
Molecular Microbiology, 2017
SummaryNutritional restrictions such as calorie restrictions are known to increase the lifespan of various organisms. Here, we found that a restriction of sulfur extended the chronological lifespan (CLS) of the fission yeast Schizosaccharomyces pombe. The restriction decreased cellular size, RNA content, and ribosomal proteins and increased sporulation rate. These responses depended on Ecl1 family genes, the overexpression of which results in the extension of CLS. We also showed that the Zip1 transcription factor results in the sulfur restriction‐dependent expression of the ecl1+ gene. We demonstrated that a decrease in ribosomal activity results in the extension of CLS. Based on these observations, we propose that sulfur restriction extends CLS through Ecl1 family genes in a ribosomal activity‐dependent manner.
Chronological Aging in Saccharomyces cerevisiae
Sub-cellular biochemistry, 2012
The two paradigms to study aging in Saccharomyces cerevisiae are the chronological life spanchronological life span (CLS) and the replicative life spanreplicative life span (RLS). The chronological life span is a measure of the mean and maximum survival time of non-dividing yeast populations while the replicative life span is based on the mean and maximum number of daughter cells generated by an individual mother cell before cell division stops irreversibly. Here we review the principal discoveries associated with yeast chronological aging and how they are contributing to the understanding of the aging process and of the molecular mechanisms that may lead to healthy aging in mammals. We will focus on the mechanisms of life span regulation by the Tor/Sch9Tor/Sch9 and the Ras/adenylateRas/adenylate cyclase/PKA pathwayscyclase/PKA pathways with particular emphasis on those implicating age-dependent oxidativeoxidative stressstress and DNA damage/repairDNA damage/repair .
The Fission Yeastphp2Mutant Displays a Lengthened Chronological Lifespan
Bioscience, Biotechnology, and Biochemistry, 2013
The Schizosaccharomyces pombe php2 þ gene encodes a subunit of the CCAAT-binding factor complex. We found that disruption of the php2 þ gene extended the chronological lifespan of the fission yeast. Moreover, the lifespan of the Áphp2 mutant was barely extended under calorie restricted (CR) conditions. Many other phenotypes of the Áphp2 mutant resembled those of wild-type cells grown under CR conditions, suggesting that the Áphp2 mutant might undergo CR. The mutant also showed low respiratory activity concomitant with decreased expression of the cyc1 þ and rip1 þ genes, both of which are involved in mitochondrial electron transport. On the basis of a chromatin immunoprecipitation assay, we determined that Php2 binds to a DNA region upstream of cyc1 þ and rip1 þ in S. pombe. Here we discuss the possible mechanisms by which the chronological lifespan of Áphp2 mutant is extended.
Fission Yeast and Other Yeasts as Emergent Models to Unravel Cellular Aging in Eukaryotes
Journals of Gerontology Series A-biological Sciences and Medical Sciences, 2010
In the past years, simple organisms such as yeasts and worms have contributed a great deal to aging research. Studies pioneered in Saccharomyces cerevisiae were useful to elucidate a signifi cant number of molecular mechanisms underlying cellular aging and to discover novel longevity genes. Importantly, these genes proved many times to be conserved in multicellular eukaryotes. Consequently, such discovery approaches are being extended to other yeast models, such as Schizosaccharomyces pombe , Candida albicans , Kluyveromyces lactis , and Cryptococcus neoformans . In fi ssion yeast, researchers have found links between asymmetrical cell division and nutrient signaling pathways with aging. In this review, we discuss the state of knowledge on the mechanisms controlling both replicative and chronological aging in S pombe and the other emergent yeast models.