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Sirtuin 1

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**Function and Activation of Sirtuin 1**:
Sirtuin 1 is a member of the sirtuin protein family involved in regulating epigenetic gene silencing and suppressing rDNA recombination.
– It affects the activity of PGC1-alpha/ERR-alpha complex and deacetylates and deactivates the p53 protein.
– Activation of SIRT1 can be achieved through compounds like resveratrol, metformin, and other plant-derived polyphenols.
– Resveratrol, in particular, increases SIRT1 expression and directly activates SIRT1 against non-modified peptide substrates.
– SIRT1 activation has been linked to improving insulin sensitivity, modulating energy expenditure, and playing a role in T helper 17 cell activation.

**Interactions and Regulation of Sirtuin 1**:
– SIRT1 interacts with ERR-alpha, AIRE, and has numerous direct interactions in interactomic studies.
– Inhibition of SIRT1 can occur due to factors like high DNA damage reducing NAD+ levels and chronic inflammation affecting SIRT1 levels.
– SIRT1 regulation involves the AMPK signaling pathway, natural products targeting diabetes treatment, and modulators studied in liver injury.
– Targeting SIRT1 for metabolism improvement involves focusing on NAD+ levels and its essential role in central immunological tolerance.
– SIRT1 is a key player in NAD metabolism, potentially possessing protein ADP-ribosyltransferase activity.

**Sir2 and Longevity Research**:
– Sir2, the first gene of the sirtuin family, is crucial for an organism’s response to stresses and lifespan extension.
– Sir2 activity results in chromatin silencing, preventing rDNA circles’ accumulation and contributing to longevity.
– Studies on Sir2 have shown a 50% reduction in lifespan upon its deletion, highlighting its importance in regulating longevity.
– Research findings suggest that Sir2, along with other sirtuins, play a role in regulating lifespan and longevity through various pathways like calorie restriction.

**Molecular Mechanisms and Therapeutic Potential**:
– SIRT1 is involved in modulating NF-κB-dependent transcription, cell survival, and has antagonistic crosstalk with NF-κB in regulating inflammation.
– The SIRT1-NF-κB axis is a potential therapeutic target for alleviating inflammation in liver disease.
– Understanding SIRT1’s role in DNA repair, homologous recombination, and its link to human diseases could have therapeutic implications.
– Chronic inflammation (inflammaging) and the NF-kappaB pathway are associated with age-related diseases and can be modulated by SIRT1 deacetylase.
– Antagonistic crosstalk between SIRT1, PARP-1, and -2 regulates chronic inflammation in aging and metabolic diseases.

**Research Impact and External Links**:
– SIRT1’s implications in aging, metabolism, and neurodegeneration are being explored through various research studies.
– SIRT1 activation by allosteric activators has shown evidence in inhibiting steatosis, steatohepatitis, and improving metabolism.
– Research on SIRT1’s role in neurodegenerative diseases, interactomics, and phylogenetic classification of SIRT1-like proteins is ongoing.
– External links provide additional resources for studying SIRT1, its human gene location, and related hydrolases.
– Categorization of SIRT1 includes its gene location on human chromosome 10, association with aging-related proteins, and relevant webarchive templates.

Sirtuin 1 (Wikipedia)

Sirtuin 1, also known as NAD-dependent deacetylase sirtuin-1, is a protein that in humans is encoded by the SIRT1 gene.

Available structures
PDBOrtholog search: PDBe RCSB
AliasesSIRT1, SIR2L1, SIR2, hSIR2, SIR2alpha, Sirtuin 1
External IDsOMIM: 604479 MGI: 2135607 HomoloGene: 56556 GeneCards: SIRT1
RefSeq (mRNA)



RefSeq (protein)



Location (UCSC)Chr 10: 67.88 – 67.92 MbChr 10: 63.15 – 63.22 Mb
PubMed search
View/Edit HumanView/Edit Mouse

SIRT1 stands for sirtuin (silent mating type information regulation 2 homolog) 1 (S. cerevisiae), referring to the fact that its sirtuin homolog (biological equivalent across species) in yeast (Saccharomyces cerevisiae) is Sir2. SIRT1 is an enzyme located primarily in the cell nucleus that deacetylates transcription factors that contribute to cellular regulation (reaction to stressors, longevity).

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