Caloric restriction and aging (Homo sapiens)

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1Caloric restriction(+) Stress resistance(+) Lifespan and healthspanAutophagyATPmTORNAMPTAMPKSIRT1insulin/IGF1AMPNADPGC-1aFOXOAKTp53MitochondrialbiogenisisOxidative stress


Caloric restriction leads to a decrease in the ATP/AMP ratio, thereby activating the key nutrient sensor of the body: AMPK.

AMPK then blocks mTOR function, as mTOR has an important role in regulating the balance between cell growth and autophagy, nutrient decrease leads to the induction of autophagy. AMPK stimulates NAMPT function and PGC-1a release. NAMPT converts nicotinamide to nicotinamide mononucleotide for NAD+ synthesis. PGC-1a is the regulator of mitochondrial biosynthesis (increasing mitochondrial cell mass to produce more ATP) which thus will increase if more PGC-1a is released. Levels of NAD rise during caloric restriction leading to increased SIRT1 activity. SIRT1 blocks the Insulin/IGF-1 pathway. This is a very complex and paradoxal tissue, which need further investigation/research. Increased SIRT1 activity leads to activation of FOXO/p53 genes. FOXOs become phosphorylated by AKT and this may attenuate apoptotic stimuli and reduce antioxidative stress expression. In the end these effects result in increased stress resistance and improved lifespan and health span.

Proteins on this pathway have targeted assays available via the CPTAC Assay Portal

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Ontology Terms



  1. López-Otín C, Blasco MA, Partridge L, Serrano M, Kroemer G; ''The hallmarks of aging.''; Cell, 2013 PubMed Europe PMC


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106347view21:35, 21 August 2019KhanspersModified description
105548view06:10, 9 August 2019KhanspersModified description
96444view08:33, 15 March 2018EgonwReplaced secondary ChEBI identifiers with primary identifiers.
95530view20:33, 20 December 2017EgonwModified description
95529view20:31, 20 December 2017EgonwFixed character encoding.
95505view14:17, 18 December 2017DeSlAdded IDs for metabolites.
95504view14:14, 18 December 2017DeSlOntology Term : 'autophagy pathway' added !
95503view14:13, 18 December 2017DeSlOntology Term : 'oxidative stress response pathway' added !
95502view14:12, 18 December 2017DeSlOntology Term : 'aging pathway' added !
95501view14:12, 18 December 2017DeSlModified description
95500view14:11, 18 December 2017DeSlNew pathway

External references


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NameTypeDatabase referenceComment
AKTGeneProductENSG00000142208 (Ensembl)
AMPMetaboliteCHEBI:16027 (ChEBI)
AMPKGeneProductENSG00000131791 (Ensembl)
ATPMetaboliteCHEBI:15422 (ChEBI)
FOXOGeneProductENSG00000214295 (Ensembl)
NADMetaboliteCHEBI:13389 (ChEBI)
NAMPTGeneProductENSG00000105835 (Ensembl)
PGC-1aGeneProductENSG00000109819 (Ensembl)
SIRT1GeneProductENSG00000096717 (Ensembl)
insulin/IGF1GeneProductENSG00000017427 (Ensembl)
mTORGeneProductENSG00000198793 (Ensembl)
p53GeneProductENSG00000141510 (Ensembl)

Annotated Interactions

No annotated interactions

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