RGD Reference Report - Ink4a/Arf expression is a biomarker of aging. - Rat Genome Database

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Ink4a/Arf expression is a biomarker of aging.

Authors: Krishnamurthy, J  Torrice, C  Ramsey, MR  Kovalev, GI  Al-Regaiey, K  Su, L  Sharpless, NE 
Citation: Krishnamurthy J, etal., J Clin Invest 2004 Nov;114(9):1299-307.
RGD ID: 1358479
Pubmed: PMID:15520862   (View Abstract at PubMed)
PMCID: PMC524230   (View Article at PubMed Central)
DOI: DOI:10.1172/JCI22475   (Journal Full-text)

The Ink4a/Arf locus encodes 2 tumor suppressor molecules, p16INK4a and Arf, which are principal mediators of cellular senescence. To study the links between senescence and aging in vivo, we examined Ink4a/Arf expression in rodent models of aging. We show that expression of p16INK4a and Arf markedly increases in almost all rodent tissues with advancing age, while there is little or no change in the expression of other related cell cycle inhibitors. The increase in expression is restricted to well-defined compartments within each organ studied and occurs in both epithelial and stromal cells of diverse lineages. The age-associated increase in expression of p16INK4a and Arf is attenuated in the kidney, ovary, and heart by caloric restriction, and this decrease correlates with diminished expression of an in vivo marker of senescence, as well as decreased pathology of those organs. Last, the age-related increase in Ink4a/Arf expression can be independently attributed to the expression of Ets-1, a known p16INK4a transcriptional activator, as well as unknown Ink4a/Arf coregulatory molecules. These data suggest that expression of the Ink4a/Arf tumor suppressor locus is a robust biomarker, and possible effector, of mammalian aging.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to caloric restriction  IEP 1358479; 1358479; 1358479 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cdkn2a  (cyclin-dependent kinase inhibitor 2A)
Cdkn2a_v1  (cyclin-dependent kinase inhibitor 2A, variant 1)
Cdkn2a_v2  (cyclin-dependent kinase inhibitor 2A, variant 2)

Additional Information