Diseases of Cellular Senescence

Stable Identifier
R-HSA-9630747
DOI
Type
Pathway
Species
Homo sapiens
ReviewStatus
5/5
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Cellular senescence plays an important role in normal aging, as well as in age-related diseases. Impaired cellular senescence contributes to malignant transformation and cancer development. Presence of an excessive number of senescent cells that are not cleared by the immune system, however, promotes tissue inflammation and creates a microenvironment suitable for growth of neighboring malignant cells. Besides cancer, senescence is also involved in atherosclerosis, osteoarthritis and diabetes (Childs et al. 2015, He and Sharpless 2017).

Evasion of oncogene-induced senescence, at least in cell culture, can occur due to loss-of-function (LOF) mutation in the CDKN2A gene product p16INK4A that acts as a cyclin-dependent kinase inhibitor (reviewed in Sharpless and Sherr 2015). LOF mutations in the CDKN2A gene that affect its other protein product, p14ARF, involved in stabilization of TP53 protein (p53), can contribute to evasion of oncogene-induced senescence (reviewed in Fontana et al. 2019).

LOF mutations in p16INK4A and p14ARF also contribute to evasion of oxidative stress-induced senescence (reviewed in Sharpless and Sherr 2015, and Fontana et al. 2019, respectively).
Literature References
PubMed ID Title Journal Year
26105537 Forging a signature of in vivo senescence

Sharpless, NE, Sherr, CJ

Nat. Rev. Cancer 2015
28575665 Senescence in Health and Disease

He, S, Sharpless, NE

Cell 2017
26646499 Cellular senescence in aging and age-related disease: from mechanisms to therapy

Childs, BG, van Deursen, JM, Baker, DJ, Durik, M

Nat. Med. 2015
Participants
Participates
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
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