Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life span

Chiocchetti, Andreas G.; Zhou, Jia; Zhu, Huashun; Karl, Thomas R.; Haubenreisser, Olaf; Rinnerthaler, Mark; Heeren, Gino; Oender, Kamil; Bauer, Johann; Hintner, Helmut; Breitenbach, Michael; Breitenbach-Koller, Hannelore

doi:10.1016/j.exger.2006.11.002

Cited by 105 publications

(94 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Similarly, C. elgans lifespan was extended and stress resistance enhanced when translation was inhibited when synthesis of eleven ribosomal proteins was suppressed using inhibiting-RNAs (RNAi) (Hansen et al, 2007). Furthermore, certain ribosomal protein defects have beneficial effects on yeast longevity (Chiocchetti et al, 2007). While the explanation of these effects is debated (Kaeberlein and Kennedy, 2007), it is likely that the lowered rate of bulk protein synthesis, resulting from the lowered translation initiation frequency, also decreases biosynthesis of erroneous proteins (Hipkiss, 2007a).…”

Section: Carnosine Slowing Protein Synthesis and Ageingmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

View full text Add to dashboard Cite

Carnosine ( -alanyl-L-histidine) has described as a forgotten and enigmatic dipeptide. Carnosine's enigma is particularly exemplified by its apparent anti-ageing actions; it suppresses cultured human fibroblast senescence and delays ageing in senescence-accelerated mice and Drosophila, but the mechanisms reponsible remain uncertain. In addition to carnosine's well-documented anti-oxidant, anti-glycating, aldehyde-scavenging and toxic metal-ion chelating properties, its ability to influence the metabolism of altered polypeptides, whose accumulation characterises the senescent phenotype, should also be considered. When added to cultured cells, carnosine was found in a recent study to suppress phosphorylation of the translational initiation factor eIF4E resulting in decreased translation frequency of certain mRNA species. Mutations in the gene coding for eIF4E in nemtodes extend organism lifespan, hence carnosine's anti-ageing effects may be a consequence of decreased error-protein synthesis which in turn lowers formation of protein carbonyls and increases protease availability for degradation of polypeptides altered postsynthetically. Other studies have revealed carnosine-induced upregulation of stress protein expression and nitric oxide synthesis, both of which may stimulate proteasomal elimination of altered proteins. Some anti-convulsants can enhance nematode longevity and suppress the effects of a protein repair defect in mice, and as carnosine exerts anti-convulsant effects in rodents, it is speculated that the dipeptide may participate in the repair of protein isoaspartyl groups. These new observations only add to the enigma of carnosine's real in vivo functions. More experimentation is clearly required. ACCEPTED MANUSCRIPT 3 Carnosine and ageing.The naturally-occurring dipeptide carnosine ( -alanyl-L-histidine) has been described as forgotten and enigmatic (Bauer, 2005): the present paper is an attempt to rectify the former opinion, but, however only adds to the latter view. Amongst carnosine's enigmatic properties are its apparent anti-ageing actions; the dipeptide is one of a very few naturally-occurring compounds which suppresses cell senescence, induces rejuvenating effects Holliday, 1994 and, and protects against telomere shortening (Shao et al., 2004) in cultured human fibroblasts. The dipeptide also extends the life-span of senescence-accelerated mice (Yuneva et al., 1999) and Drosophila (Yuneva et al., 2002). There are many possible mechanisms by which carnosine exerts these anti-ageing actions however, some of which were summarized a decade ago (Hipkiss, 1998). Meanwhile there have been a number of publications suggesting further possible routes by which carnosine could suppress

show abstract

Section: Carnosine Slowing Protein Synthesis and Ageingmentioning

confidence: 99%

On the enigma of carnosine’s anti-ageing actions

Hipkiss¹

2009

Experimental Gerontology

View full text Add to dashboard Cite

show abstract

“…Deletion of a single ribosomal protein gene has been shown to extend life span (Kaeberlein et al, 2005b;Chiocchetti et al, 2007), so this global down-regulation would be expected to contribute to the longevity of this strain.…”

Section: Transcripts That Influence Replicative Life Span Arementioning

confidence: 99%

Budding YeastSSD1-VRegulates Transcript Levels of Many Longevity Genes and Extends Chronological Life Span in Purified Quiescent Cells

Qin

et al. 2009

MBoC

View full text Add to dashboard Cite

Ssd1 is an RNA-binding protein that affects literally hundreds of different processes and is polymorphic in both wild and lab yeast strains. We have used transcript microarrays to compare mRNA levels in an isogenic pair of mutant (ssd1-d) and wild-type (SSD1-V) cells across the cell cycle. We find that 15% of transcripts are differentially expressed, but there is no correlation with those mRNAs bound by Ssd1. About 20% of cell cycle regulated transcripts are affected, and most show sharper amplitudes of oscillation in SSD1-V cells. Many transcripts whose gene products influence longevity are also affected, the largest class of which is involved in translation. Ribosomal protein mRNAs are globally down-regulated by SSD1-V. SSD1-V has been shown to increase replicative life span¤ and we show that SSD1-V also dramatically increases chronological life span (CLS). Using a new assay of CLS in pure populations of quiescent prototrophs, we find that the CLS for SSD1-V cells is twice that of ssd1-d cells. INTRODUCTIONSsd1 is an RNA-binding protein (Uesono et al., 1997;Hogan et al., 2008) that can be distinguished from the hundreds of other RNA-binding proteins by its unusual properties. First of all, ssd1 is highly pleiotropic. This locus has at least nine different names because of its having been identified in genetic screens for its effect on minichromosome stability, stress tolerance, membrane trafficking, and cell wall integrity, among other things Kosodo et al., 2001;Vannier et al., 2001;Reinke et al., 2004). Systematic global screens have identified ϳ200 genes that show genetic or physical interactions with Ssd1 (Reguly et al., 2006). These genes show a striking enrichment (Hong et al., 2008) for posttranslational modifiers (p ϭ 10 Ϫ14 ), including 19 kinases and nine histone deacetylases, and genes involved in the cell cycle and cell morphogenesis (p ϭ 10 Ϫ8 ). ssd1 mutants display sensitivity to high osmolarity, caffeine, fungicides¤ and numerous other compounds, which suggests a role for this protein in the maintenance of cell wall integrity (Ibeas et al., 2001;Parsons et al., 2004), but its mechanism of action remains obscure.Despite, or perhaps because of, its impact on so many different cellular functions, SSD1 is a common site of variation in both laboratory strains and natural populations of budding yeast (Wheeler et al., 2003). One possible explanation is that SSD1-V, which encodes the full-length "wildtype" protein, reduces the virulence of Saccharomyces cerevisiae in one mouse model (Wheeler et al., 2003), but SSD1-V is critical in Candida (Gank et al., 2008) and several fungal pathogens of plants for evading their hosts' defense systems (Tanaka et al., 2007). In most cases, genetic interactions with SSD1-V are positive, whereas the premature termination alleles (ssd1-d) cause lethality or a more extreme phenotype. One important exception is the RAM signaling pathway mutants, tao3 (Du and Novick, 2002), and cbk1 (Tong et al., 2001;Jorgensen et al., 2002), whose loss of function is lethal if the SSD1-V a...

show abstract

“…Similarly, deletion of GCN4 reduced lifespan extension by dietary restriction, tor1D and sch9D (yeast S6 kinase). Another report indicated that deletion of one small subunit component could also extend yeast replicative lifespan [69], again pointing to additional mechanisms. Finally, while reduced expression of worm RPGs also leads to enhanced longevity, the involvement of the GCN4 orthologue, atf-5, is currently unknown and, since reduced expression of both 40S and 60S subunits can promote longevity, mechanistic differences are likely.…”

Section: Introductionmentioning

confidence: 99%

“…Mutation of other translation initiation factors is associated with enhanced longevity in yeast and worms [1,16,41], as well as reduced expression of ribosomal protein genes (RPGs) [41,68,69]. The latter effect has been best studied via the yeast replicative ageing assay, where the lifespan of every viable RPG knockout was determined.…”

Section: Introductionmentioning

confidence: 99%

TOR and ageing: a complex pathway for a complex process

McCormick

Tsai

Kennedy

2011

Phil. Trans. R. Soc. B

View full text Add to dashboard Cite

Studies in invertebrate model organisms have led to a wealth of knowledge concerning the ageing process. But which of these discoveries will apply to ageing in humans? Recently, an assessment of the degree of conservation of ageing pathways between two of the leading invertebrate model organisms, Saccharomyces cerevisiae and Caenorhabditis elegans, was completed. The results (i) quantitatively indicated that pathways were conserved between evolutionarily disparate invertebrate species and (ii) emphasized the importance of the TOR kinase pathway in ageing. With recent findings that deletion of the mTOR substrate S6K1 or exposure of mice to the mTOR inhibitor rapamycin result in lifespan extension, mTOR signalling has become a major focus of ageing research. Here, we address downstream targets of mTOR signalling and their possible links to ageing. We also briefly cover other ageing genes identified by comparing worms and yeast, addressing the likelihood that their mammalian counterparts will affect longevity.

show abstract

Ribosomal proteins Rpl10 and Rps6 are potent regulators of yeast replicative life span

Cited by 105 publications

References 43 publications

On the enigma of carnosine’s anti-ageing actions

On the enigma of carnosine’s anti-ageing actions

Budding YeastSSD1-VRegulates Transcript Levels of Many Longevity Genes and Extends Chronological Life Span in Purified Quiescent Cells

TOR and ageing: a complex pathway for a complex process

Contact Info

Product

Resources

About