HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Ink4a/Arf links senescence and aging.

Abstract
The mammalian INK4a/ARF locus encodes two linked tumor suppressor proteins, p16INK4a and ARF, which respectively regulate the retinoblastoma (RB) and p53 pathways. Genetic data have firmly established that both proteins possess significant in vivo tumor suppressor activity. In addition to their non-overlapping roles in preventing cancer, one or both proteins are induced under certain circumstances in most cultured murine and human cell types, and thereby are critical effectors of senescence. Likewise, data from murine models have suggested that this anti-cancer growth inhibitory activity of the locus can similarly affect permanent growth arrest in vivo. When such in vivo senescence occurs in a cell possessing self-renewal potential (e.g. a tissue stem cell), there is an attendant decline in the regenerative capabilities of the organ maintained by that stem cell. In turn, the concomitant decline of this stem cell reserve is a cardinal feature of mammalian aging. Expression of the INK4a/ARF locus, therefore, appears not only to be a major suppressor of cancer, but also an effector of mammalian aging.
AuthorsNorman E Sharpless
JournalExperimental gerontology (Exp Gerontol) 2004 Nov-Dec Vol. 39 Issue 11-12 Pg. 1751-9 ISSN: 0531-5565 [Print] England
PMID15582292 (Publication Type: Journal Article, Review)
Chemical References
  • Cyclin-Dependent Kinase Inhibitor p16
  • Retinoblastoma Protein
  • Tumor Suppressor Protein p53
Topics
  • Adult
  • Aged
  • Aging (genetics)
  • Animals
  • Cellular Senescence (physiology)
  • Cyclin-Dependent Kinase Inhibitor p16 (genetics, metabolism)
  • Genes, Tumor Suppressor
  • Humans
  • Mammals (physiology)
  • Middle Aged
  • Retinoblastoma Protein (metabolism)
  • Stem Cells (physiology)
  • Tumor Suppressor Protein p53 (metabolism)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: