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'''Sir2''' (whose [[homology (biology)|homolog]] in [[mammal]]s is known as '''SIRT1''', '''SIR2L1''' or '''Sir2α''') was the first gene of the [[sirtuin]] genes to be found. It was found in [[budding yeast]], and, since then, members of this [[Conservation (genetics)|highly conserved]] family have been found in nearly all organisms studied.<ref>{{cite journal |
'''Sir2''' (whose [[homology (biology)|homolog]] in [[mammal]]s is known as '''SIRT1''', '''SIR2L1''' or '''Sir2α''') was the first gene of the [[sirtuin]] genes to be found. It was found in [[budding yeast]], and, since then, members of this [[Conservation (genetics)|highly conserved]] family have been found in nearly all organisms studied.<ref>{{cite journal |pages=793–8 |doi=10.1006/bbrc.2000.3000}}</ref> Sirtuins are hypothesized to play a key role in an organism's response to stresses (such as heat or starvation) and to be responsible for the lifespan-extending effects of [[calorie restriction]].<ref name=sinclair>{{cite journal |pages=48–51, 54–7 |doi=10.1038/scientificamerican0306-48}}</ref> |
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==Nomenclature in various organisms== |
==Nomenclature in various organisms== |
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The three letter yeast gene symbol ''Sir'' stands for <u>S</u>ilent <u>I</u>nformation <u>R</u>egulator while the number ''2'' is representative of the fact that it was the second SIR gene discovered and characterized.<ref>{{cite journal | |
The three letter yeast gene symbol ''Sir'' stands for <u>S</u>ilent <u>I</u>nformation <u>R</u>egulator while the number ''2'' is representative of the fact that it was the second SIR gene discovered and characterized.<ref>{{cite journal |last1=Rine |first1=Jasper |last2=Herskowitz |first2=Ira |title=Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae |journal=Genetics |volume=116 |issue=1 |pages=9–22 |year=1987 |month=May |pmid=3297920 |pmc=1203125 |url=http://www.genetics.org/cgi/pmidlookup?view=long&pmid=3297920}}</ref> The term sirtuin is derived from Sir2 and stands for ''<u>S</u>ilent <u>I</u>nformation <u>R</u>eg<u>u</u>lator <u>T</u>wo (Sir2) prote<u>in</u>''.<ref name="pmid15128440">{{cite journal |doi=10.1186/gb-2004-5-5-224}}</ref> |
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The name Sir2 is used for the enzyme in the yeast ''[[Saccharomyces cerevisiae]]'' (where it was first discovered), in the fruit fly ''[[Drosophila melanogaster]]'', while in the roundworm, ''[[Caenorhabditis elegans]]'', Sir-2.1 is used to denote the gene product most similar to yeast Sir2 in structure and activity.<ref>[http://wormbase.org/db/seq/protein?name=sir-2.1;class=Protein: WormBase Protein Summary: Sir-2.1]</ref><ref> |
The name Sir2 is used for the enzyme in the yeast ''[[Saccharomyces cerevisiae]]'' (where it was first discovered), in the fruit fly ''[[Drosophila melanogaster]]'', while in the roundworm, ''[[Caenorhabditis elegans]]'', Sir-2.1 is used to denote the gene product most similar to yeast Sir2 in structure and activity.<ref>[http://wormbase.org/db/seq/protein?name=sir-2.1;class=Protein: WormBase Protein Summary: Sir-2.1]</ref><ref><nowiki>http://mediwire.skyscape.com/main/Default.aspx?P=Content&ArticleID=174239</nowiki>{{dead link}} Skyscape Content: Do antiaging approaches promote longevity?</ref> |
||
The various sirtuins in mammals are referred to as SIRT1-SIRT7 with SIRT1 being the mammalian ortholog closest in structure and function to Sir2.<ref>{{cite journal |
The various sirtuins in mammals are referred to as SIRT1-SIRT7 with SIRT1 being the mammalian ortholog closest in structure and function to Sir2.<ref>{{cite journal |pages=3173–85 |doi=10.1128/MCB.23.9.3173-3185.2003}}</ref><ref>{{cite journal |pages=793–8 |doi=10.1006/bbrc.2000.3000}}</ref> |
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==Method of action and observed effects== |
==Method of action and observed effects== |
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Sirtuins act primarily by removing [[acetyl]] groups from lysine residues within proteins in the presence of [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]]; thus, they are classified as "NAD<sup>+</sup>-dependent deacetylases" and have [[EC number]] 3.5.1.<ref>[http://www.ebi.ac.uk/interpro/IEntry?ac=IPR003000 The Sir2 protein family] from [[EMBL]]'s InterPro database</ref> They add the acetyl group from the protein to the [[Adenosine diphosphate ribose|ADP-ribose]] component of NAD<sup>+</sup> to form O-acetyl-ADP-ribose. |
Sirtuins act primarily by removing [[acetyl]] groups from lysine residues within proteins in the presence of [[Nicotinamide adenine dinucleotide|NAD<sup>+</sup>]]; thus, they are classified as "NAD<sup>+</sup>-dependent deacetylases" and have [[EC number]] 3.5.1.<ref>[http://www.ebi.ac.uk/interpro/IEntry?ac=IPR003000 The Sir2 protein family] from [[EMBL]]'s InterPro database</ref> They add the acetyl group from the protein to the [[Adenosine diphosphate ribose|ADP-ribose]] component of NAD<sup>+</sup> to form O-acetyl-ADP-ribose. |
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Sir2 is the only Class III [[histone deacetylase]] (HDAC) in budding yeast.'<ref name=pm12067588>{{cite journal |doi=10.1016/S1568-1637(02)00003-X |
Sir2 is the only Class III [[histone deacetylase]] (HDAC) in budding yeast.'<ref name=pm12067588>{{cite journal |pages=313–26 |doi=10.1016/S1568-1637(02)00003-X}}</ref> The HDAC activity of Sir2 results in tighter packaging of [[chromatin]] and a reduction in [[transcription (genetics)|transcription]] at the targeted gene locus. The silencing activity of Sir2 is most prominent at telomeric sequences, the [[Mating_of_yeast#HML_and_HMR:_the_silent_mating_cassettes|hidden MAT loci]] (HM loci), and the [[ribosome|ribosomal]] DNA (rDNA) locus (RDN1) from which [[ribosomal RNA]] is transcribed. |
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Limited [[gene expression|overexpression]] of the Sir2 [[gene]] results in a lifespan extension of about 30%,<ref name="pm12067588"/> if the lifespan is measured as the number of cell divisions the mother cell can undergo before cell death. Cocordinantly, deletion of Sir2 results in a 50% reduction in lifespan.<ref name=pm12067588 /> In particular, the silencing activity of Sir2, in complex with Sir3 and Sir4, at the HM loci prevents simultaneous expression of both mating factors which can cause sterility and shortened lifespan.<ref name=pm10521401>{{cite journal |doi=10.1101/gad.13.19.2570 |
Limited [[gene expression|overexpression]] of the Sir2 [[gene]] results in a lifespan extension of about 30%,<ref name="pm12067588"/> if the lifespan is measured as the number of cell divisions the mother cell can undergo before cell death. Cocordinantly, deletion of Sir2 results in a 50% reduction in lifespan.<ref name=pm12067588 /> In particular, the silencing activity of Sir2, in complex with Sir3 and Sir4, at the HM loci prevents simultaneous expression of both mating factors which can cause sterility and shortened lifespan.<ref name=pm10521401>{{cite journal |pages=2570–80 |doi=10.1101/gad.13.19.2570}}</ref> Additionally, Sir2 activity at the rDNA locus is correlated with a decrease in the formation of rDNA circles. Chromatin silencing, as a result of Sir2 activity, reduces [[homologous recombination]] between rDNA repeats, which is the process leading to the formation of rDNA circles. As accumulation of these rDNA circles is the primary way in which yeast are believed to "age", then the action of Sir2 in preventing accumulation of these rDNA circles is a necessary factor in yeast longevity.<ref name=pm10521401 /> |
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Starving of yeast cells leads to a similarly extended lifespan, and indeed starving increases the available amount of NAD<sup>+</sup> and reduces [[nicotinamide]], both of which have the potential to increase the activity of Sir2. Furthermore, removing the Sir2 gene eliminates the life-extending effect of caloric restriction.<ref name=Dros> |
Starving of yeast cells leads to a similarly extended lifespan, and indeed starving increases the available amount of NAD<sup>+</sup> and reduces [[nicotinamide]], both of which have the potential to increase the activity of Sir2. Furthermore, removing the Sir2 gene eliminates the life-extending effect of caloric restriction.<ref name=Dros>{{EntrezGene|34708}} Drosophilia Sir2</ref> Experiments in the [[nematode]] ''[[Caenorhabditis elegans]]'' and in the fruit fly ''[[Drosophila melanogaster]]''<ref>{{cite journal |pages=15998–6003 |doi=10.1073/pnas.0404184101}}</ref> support these findings. {{As of|2006}}, experiments in [[Mus musculus|mice]] are underway.<ref name=sinclair/> |
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However, some other findings call the above interpretation into question. If one measures the lifespan of a yeast cell as the amount of time it can live in a non-dividing stage, then silencing the Sir2 gene actually ''increases'' lifespan <ref>{{cite journal |
However, some other findings call the above interpretation into question. If one measures the lifespan of a yeast cell as the amount of time it can live in a non-dividing stage, then silencing the Sir2 gene actually ''increases'' lifespan <ref>{{cite journal |pages=655–67 |doi=10.1016/j.cell.2005.08.042 }}</ref> Furthermore, calorie restriction can substantially prolong reproductive lifespan in yeast even in the absence of Sir2.<ref>{{cite journal |doi=10.1371/journal.pbio.0020296}}</ref> |
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In organisms more complicated than yeast, it appears that Sir2 acts by deacetylation of several other proteins besides histones. |
In organisms more complicated than yeast, it appears that Sir2 acts by deacetylation of several other proteins besides histones. |
||
[[Resveratrol]] is a substance that has been shown through experiment to have a number of life-extending and health benefits in various species; it also increases the activity of Sir2, which is the postulated reason for its beneficial effects. Resveratrol is produced by plants when they are stressed, and it is possible that plants use the substance to increase their own Sir2 activity in order to survive periods of stress.<ref name=sinclair/> Although there is mounting evidence for this hypothesis, it's validity is debated.<ref>{{cite journal |
[[Resveratrol]] is a substance that has been shown through experiment to have a number of life-extending and health benefits in various species; it also increases the activity of Sir2, which is the postulated reason for its beneficial effects. Resveratrol is produced by plants when they are stressed, and it is possible that plants use the substance to increase their own Sir2 activity in order to survive periods of stress.<ref name=sinclair/> Although there is mounting evidence for this hypothesis, it's validity is debated.<ref>{{cite journal |pages=17038–45 |doi=10.1074/jbc.M500655200}}</ref><ref>{{cite journal |pages=17187–95 |doi=10.1074/jbc.M501250200}}</ref><ref name="pmid20061378">{{cite journal |pages=8340–51 |doi=10.1074/jbc.M109.088682}}</ref><ref>{{cite journal |pages=619–24 |doi=10.1111/j.1747-0285.2009.00901.x}}</ref> |
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In mammals, SIRT1 (the mammalian homolog of Sir2) has been shown to deacetylate and thereby deactivate the [[p53]] protein.<ref> |
In mammals, SIRT1 (the mammalian homolog of Sir2) has been shown to deacetylate and thereby deactivate the [[p53]] protein.<ref>{{EntrezGene|23411}} Human Sirt1</ref> SIRT1 also stimulates autophagy by preventing acetylation of proteins required for autophagy in cultured cells and embryonic and neonatal tissues. This function provides a link between sirtuin expression and the cellular response to limited nutrients due to caloric restriction.<ref>{{cite journal |pages=3374–9 |doi=10.1073/pnas.0712145105}}</ref> Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the [[PPARGC1A|PGC1-alpha]]/[[Estrogen-related receptor alpha|ERR-alpha]] complex, which are essential metabolic regulatory transcription factors.<ref name="pmid20484414">{{cite journal |pages=1349–58 |doi=10.1210/me.2009-0441}}</ref><ref name="pmid15744310">{{cite journal |pages=113–8 |doi=10.1038/nature03354}}</ref><ref name="pmid15716268">{{cite journal |pages=16456–60 |doi=10.1074/jbc.M501485200}}</ref><ref name="pmid17112576">{{cite journal |pages=1109–22 |doi=10.1016/j.cell.2006.11.013}}</ref><ref name="pmid18849969">{{cite journal |pages=269–73 |doi=10.1038/nature07349}}</ref><ref name="pmid19262508">{{cite journal |pages=1056–60 |doi=10.1038/nature07813}}</ref> |
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In the fruit fly ''Drosophilia melanogaster'', the Sir2 gene does not seem to be essential; loss of a sirtuin gene has only very subtle effects.<ref name=Dros/> However, mice lacking the SIRT1 gene (the sir2 biological equivalent) were smaller than normal at birth, often died early or became sterile.<ref>{{cite journal |
In the fruit fly ''Drosophilia melanogaster'', the Sir2 gene does not seem to be essential; loss of a sirtuin gene has only very subtle effects.<ref name=Dros/> However, mice lacking the SIRT1 gene (the sir2 biological equivalent) were smaller than normal at birth, often died early or became sterile.<ref>{{cite journal |pages=38–54 |doi=10.1128/MCB.23.1.38-54.2003}}</ref> |
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==Mammal sirtuins== |
==Mammal sirtuins== |
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| Line 34: | Line 34: | ||
* {{Gene|SIRT3}}, {{Gene|SIRT4}}, and {{Gene|SIRT5}} are active in mitochondria, the energy-producing organelles that are a part of every cell. |
* {{Gene|SIRT3}}, {{Gene|SIRT4}}, and {{Gene|SIRT5}} are active in mitochondria, the energy-producing organelles that are a part of every cell. |
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* {{Gene|SIRT6}} is active in the [[Cell nucleus|nucleus]] of the cell. |
* {{Gene|SIRT6}} is active in the [[Cell nucleus|nucleus]] of the cell. |
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* {{Gene|SIRT7}} is active in the [[nucleolus]], a compartment of the nucleus reserved for the assembly of [[ribosome]]s. Sirt7 has been shown to activate RNA Polymerase I transcription<ref>{{cite journal |
* {{Gene|SIRT7}} is active in the [[nucleolus]], a compartment of the nucleus reserved for the assembly of [[ribosome]]s. Sirt7 has been shown to activate RNA Polymerase I transcription.<ref>{{cite journal |pages=1075–80 |doi=10.1101/gad.1399706}}</ref> |
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== See also == |
== See also == |
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| Line 46: | Line 46: | ||
==External links== |
==External links== |
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*{{EntrezGene|23411}} Human Sirt1 |
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*[http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=gene&cmd=Retrieve&dopt=full_report&list_uids=23411 Human Sirt1] from NCBI's Entrez Gene database |
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*[http://genomics.senescence.info/genes/entry.php?hugo=SIRT1 Human Sirt1] in the GenAge database |
*[http://genomics.senescence.info/genes/entry.php?hugo=SIRT1 Human Sirt1] in the GenAge database |
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*[http://www.ihop-net.org/UniPub/iHOP/gismo/142188.html Sirt1] in the [[Information Hyperlinked over Proteins|iHOP]] database |
*[http://www.ihop-net.org/UniPub/iHOP/gismo/142188.html Sirt1] in the [[Information Hyperlinked over Proteins|iHOP]] database |
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Revision as of 12:19, 30 March 2011
Sir2 (whose homolog in mammals is known as SIRT1, SIR2L1 or Sir2α) was the first gene of the sirtuin genes to be found. It was found in budding yeast, and, since then, members of this highly conserved family have been found in nearly all organisms studied.[1] Sirtuins are hypothesized to play a key role in an organism's response to stresses (such as heat or starvation) and to be responsible for the lifespan-extending effects of calorie restriction.[2]
Nomenclature in various organisms
The three letter yeast gene symbol Sir stands for Silent Information Regulator while the number 2 is representative of the fact that it was the second SIR gene discovered and characterized.[3] The term sirtuin is derived from Sir2 and stands for Silent Information Regulator Two (Sir2) protein.[4]
The name Sir2 is used for the enzyme in the yeast Saccharomyces cerevisiae (where it was first discovered), in the fruit fly Drosophila melanogaster, while in the roundworm, Caenorhabditis elegans, Sir-2.1 is used to denote the gene product most similar to yeast Sir2 in structure and activity.[5][6]
The various sirtuins in mammals are referred to as SIRT1-SIRT7 with SIRT1 being the mammalian ortholog closest in structure and function to Sir2.[7][8]
Method of action and observed effects
Sirtuins act primarily by removing acetyl groups from lysine residues within proteins in the presence of NAD+; thus, they are classified as "NAD+-dependent deacetylases" and have EC number 3.5.1.[9] They add the acetyl group from the protein to the ADP-ribose component of NAD+ to form O-acetyl-ADP-ribose.
Sir2 is the only Class III histone deacetylase (HDAC) in budding yeast.'[10] The HDAC activity of Sir2 results in tighter packaging of chromatin and a reduction in transcription at the targeted gene locus. The silencing activity of Sir2 is most prominent at telomeric sequences, the hidden MAT loci (HM loci), and the ribosomal DNA (rDNA) locus (RDN1) from which ribosomal RNA is transcribed.
Limited overexpression of the Sir2 gene results in a lifespan extension of about 30%,[10] if the lifespan is measured as the number of cell divisions the mother cell can undergo before cell death. Cocordinantly, deletion of Sir2 results in a 50% reduction in lifespan.[10] In particular, the silencing activity of Sir2, in complex with Sir3 and Sir4, at the HM loci prevents simultaneous expression of both mating factors which can cause sterility and shortened lifespan.[11] Additionally, Sir2 activity at the rDNA locus is correlated with a decrease in the formation of rDNA circles. Chromatin silencing, as a result of Sir2 activity, reduces homologous recombination between rDNA repeats, which is the process leading to the formation of rDNA circles. As accumulation of these rDNA circles is the primary way in which yeast are believed to "age", then the action of Sir2 in preventing accumulation of these rDNA circles is a necessary factor in yeast longevity.[11]
Starving of yeast cells leads to a similarly extended lifespan, and indeed starving increases the available amount of NAD+ and reduces nicotinamide, both of which have the potential to increase the activity of Sir2. Furthermore, removing the Sir2 gene eliminates the life-extending effect of caloric restriction.[12] Experiments in the nematode Caenorhabditis elegans and in the fruit fly Drosophila melanogaster[13] support these findings. As of 2006[update], experiments in mice are underway.[2]
However, some other findings call the above interpretation into question. If one measures the lifespan of a yeast cell as the amount of time it can live in a non-dividing stage, then silencing the Sir2 gene actually increases lifespan [14] Furthermore, calorie restriction can substantially prolong reproductive lifespan in yeast even in the absence of Sir2.[15]
In organisms more complicated than yeast, it appears that Sir2 acts by deacetylation of several other proteins besides histones.
Resveratrol is a substance that has been shown through experiment to have a number of life-extending and health benefits in various species; it also increases the activity of Sir2, which is the postulated reason for its beneficial effects. Resveratrol is produced by plants when they are stressed, and it is possible that plants use the substance to increase their own Sir2 activity in order to survive periods of stress.[2] Although there is mounting evidence for this hypothesis, it's validity is debated.[16][17][18][19]
In mammals, SIRT1 (the mammalian homolog of Sir2) has been shown to deacetylate and thereby deactivate the p53 protein.[20] SIRT1 also stimulates autophagy by preventing acetylation of proteins required for autophagy in cultured cells and embryonic and neonatal tissues. This function provides a link between sirtuin expression and the cellular response to limited nutrients due to caloric restriction.[21] Furthermore, SIRT1 was shown to de-acetylate and affect the activity of both members of the PGC1-alpha/ERR-alpha complex, which are essential metabolic regulatory transcription factors.[22][23][24][25][26][27]
In the fruit fly Drosophilia melanogaster, the Sir2 gene does not seem to be essential; loss of a sirtuin gene has only very subtle effects.[12] However, mice lacking the SIRT1 gene (the sir2 biological equivalent) were smaller than normal at birth, often died early or became sterile.[28]
Mammal sirtuins
Seven sirtuins are known in mammals.
- SIRT1 (also known as Sir2α) is the mammal homolog of Sir2. Mice that overexpress SIRT1 show eight properties of calorie restriction, including low cholesterol, low blood glucose, and low insulin levels. They also show increased numbers of mitochondria in their neurons.
- SIRT2 is expressed mainly in the brain.
- SIRT3, SIRT4, and SIRT5 are active in mitochondria, the energy-producing organelles that are a part of every cell.
- SIRT6 is active in the nucleus of the cell.
- SIRT7 is active in the nucleolus, a compartment of the nucleus reserved for the assembly of ribosomes. Sirt7 has been shown to activate RNA Polymerase I transcription.[29]
See also
- Histone deacetylases, the class of enzymes to which yeast Sir2 belongs
- Longevity genes
- Life extension
- Sirtuins, the family of genes to which Sir2 genes are related.
References
- ^ : 793–8. doi:10.1006/bbrc.2000.3000.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ a b c : 48–51, 54–7. doi:10.1038/scientificamerican0306-48.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ Rine, Jasper; Herskowitz, Ira (1987). "Four genes responsible for a position effect on expression from HML and HMR in Saccharomyces cerevisiae". Genetics. 116 (1): 9–22. PMC 1203125. PMID 3297920.
{{cite journal}}: Unknown parameter|month=ignored (help) - ^ . doi:10.1186/gb-2004-5-5-224.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)CS1 maint: unflagged free DOI (link) - ^ WormBase Protein Summary: Sir-2.1
- ^ http://mediwire.skyscape.com/main/Default.aspx?P=Content&ArticleID=174239[dead link] Skyscape Content: Do antiaging approaches promote longevity?
- ^ : 3173–85. doi:10.1128/MCB.23.9.3173-3185.2003.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 793–8. doi:10.1006/bbrc.2000.3000.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ The Sir2 protein family from EMBL's InterPro database
- ^ a b c : 313–26. doi:10.1016/S1568-1637(02)00003-X.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ a b : 2570–80. doi:10.1101/gad.13.19.2570.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ a b EntrezGene 34708 Drosophilia Sir2
- ^ : 15998–6003. doi:10.1073/pnas.0404184101.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 655–67. doi:10.1016/j.cell.2005.08.042.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ . doi:10.1371/journal.pbio.0020296.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)CS1 maint: unflagged free DOI (link) - ^ : 17038–45. doi:10.1074/jbc.M500655200.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)CS1 maint: unflagged free DOI (link) - ^ : 17187–95. doi:10.1074/jbc.M501250200.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)CS1 maint: unflagged free DOI (link) - ^ : 8340–51. doi:10.1074/jbc.M109.088682.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)CS1 maint: unflagged free DOI (link) - ^ : 619–24. doi:10.1111/j.1747-0285.2009.00901.x.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ EntrezGene 23411 Human Sirt1
- ^ : 3374–9. doi:10.1073/pnas.0712145105.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 1349–58. doi:10.1210/me.2009-0441.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 113–8. doi:10.1038/nature03354.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 16456–60. doi:10.1074/jbc.M501485200.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)CS1 maint: unflagged free DOI (link) - ^ : 1109–22. doi:10.1016/j.cell.2006.11.013.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 269–73. doi:10.1038/nature07349.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 1056–60. doi:10.1038/nature07813.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 38–54. doi:10.1128/MCB.23.1.38-54.2003.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help) - ^ : 1075–80. doi:10.1101/gad.1399706.
{{cite journal}}: Cite journal requires|journal=(help); Missing or empty|title=(help)
External links
- EntrezGene 23411 Human Sirt1
- Human Sirt1 in the GenAge database
- Sirt1 in the iHOP database