NAD metabolism, sirtuins and aging (Homo sapiens)

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1Cockayne syndromeDecreased insulin secretionHigh-fat dietIncreased inflammationPossible therapeutic interventionLegendInflammationDNA DamageAgingNF-kBNicotinamide ribosideReservatrolPARP1NAMPTNADFOXO1P7C3TFAMHIF1ASIRT1ROS1FOXO3PGC-1aTORC2PPARGPancreasXeroderma pigmentosumAtaxia telangiectasiaPARP inhibitorsSIRT3BrainSkeletal muscleLiverDecreased cognitive functionDecreased mitochondrial functionDecreased insulin sensitivity


Description

NAD+ metabolism, sirtuins, and aging.

Activation of polyADP ribose polymerase by DNA damage and decreased expression of nicotinamide phosphoribosyltransferase is associated with inflammation and aging. Both lead to decreased NAD+ levels and activities of all sirtuins (we focus on SIRT1, 3, and 5). Mitochondrial function is diminished by decreased SIRT3 and 5 activity, leading to mitochondrial protein hyperacetylation and hypersuccinylation. Decreased SIRT1 is associated with decreased immunity and other metabolic and cellular abnormalities that accelerate aging. Possible therapies are illustrated. BAT, brown-adipose tissue; NAMPT, nicotinamide phosphoribosyltransferase; PARP, poly (ADP ribose) polymerase.

Description and data for the pathway from Verdin lab, Gladstone Institutes. https://gladstone.org/our-science/people/eric-verdin

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Quality Tags

Ontology Terms

 

Bibliography

  1. Verdin E; ''NAD⁺ in aging, metabolism, and neurodegeneration.''; Science, 2015 PubMed Europe PMC Scholia
  2. Kolthur-Seetharam U, Dantzer F, McBurney MW, de Murcia G, Sassone-Corsi P; ''Control of AIF-mediated cell death by the functional interplay of SIRT1 and PARP-1 in response to DNA damage.''; Cell Cycle, 2006 PubMed Europe PMC Scholia
  3. Rajamohan SB, Pillai VB, Gupta M, Sundaresan NR, Birukov KG, Samant S, Hottiger MO, Gupta MP; ''SIRT1 promotes cell survival under stress by deacetylation-dependent deactivation of poly(ADP-ribose) polymerase 1.''; Mol Cell Biol, 2009 PubMed Europe PMC Scholia

History

View all...
CompareRevisionActionTimeUserComment
128523view14:27, 11 February 2024EweitzNudge text into alignment
128522view02:42, 11 February 2024EweitzUpgrade disease nodes
128521view01:28, 11 February 2024EweitzEconomize layout, refine legend, standardize case
121716view14:03, 26 February 2022EweitzUse gene symbol
118942view22:32, 4 June 2021EweitzOntology Term : 'aging pathway' added !
118941view22:32, 4 June 2021EweitzOntology Term : 'Sirtuin mediated pathway' added !
106745view13:22, 17 September 2019MaintBotHMDB identifier normalization
106655view21:16, 12 September 2019KhanspersModified description
105656view05:15, 10 August 2019KhanspersModified description
94184view13:55, 25 August 2017Mkutmonadded missing metabolite identifier
92696view19:24, 28 June 2017Mkutmonremoved undefined xref
88178view16:25, 29 July 2016JmeliusOntology Term : 'classic metabolic pathway' added !
85545view23:30, 27 May 2016AlexanderPicoUpdated layout and groupings
85544view23:17, 27 May 2016AlexanderPicoQuick edit to datanode annotation or property
85530view18:53, 26 May 2016Khanspersfixed unconnected interactions
85439view20:40, 15 May 2016SusanQuick edit to datanode annotation or property
85406view05:09, 13 May 2016Khanspersinteractions
85394view05:35, 12 May 2016Khansperslayout
85393view05:32, 12 May 2016Khanspersadded literature references
85392view18:32, 11 May 2016Khanspersupdate to interactions
85236view23:18, 3 May 2016Khanspersadded identifier to reservatrol
85235view23:10, 3 May 2016KhanspersModified description
85234view23:07, 3 May 2016Khanspersoverhaul
85231view04:59, 3 May 2016KhanspersModified description
85230view04:57, 3 May 2016KhanspersModified description
85227view20:08, 2 May 2016Khanspersrearrange
84991view20:35, 4 April 2016KhanspersPeriodical save, work in progress
84988view20:25, 4 April 2016KhanspersNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
FOXO1GeneProductENSG00000150907 (Ensembl)
FOXO3GeneProductENSG00000118689 (Ensembl)
HIF1AGeneProductENSG00000100644 (Ensembl)
NADMetaboliteHMDB00902 (HMDB)
NAMPTGeneProductENSG00000105835 (Ensembl)
NF-kBGeneProduct
Nicotinamide ribosideMetaboliteHMDB00855 (HMDB)
P7C3GeneProduct
PARP inhibitorsGeneProduct
PARP1GeneProductENSG00000143799 (Ensembl)
PGC-1aGeneProductENSG00000108064 (Ensembl)
PPARGGeneProductENSG00000132170 (Ensembl)
ROS1GeneProductENSG00000047936 (Ensembl)
ReservatrolMetabolite
SIRT1GeneProductENSG00000096717 (Ensembl)
SIRT3GeneProductENSG00000142082 (Ensembl)
TFAMGeneProductENSG00000108064 (Ensembl)
TORC2GeneProductENSG00000108064 (Ensembl)

Annotated Interactions

No annotated interactions

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