Entry
Name
Cellular senescence - Homo sapiens (human)
Description
Cellular senescence is a state of irreversible cellular arrest and can be triggered by a number of factors, such as telomere shortening, oncogene activation, irradiation, DNA damage and oxidative stress. It is characterized by enlarged flattened morphology, senescence-associated beta-galactosidase (SA-b-gal) activity, secretion of inflammatory cytokines, growth factors and matrix metalloproteinases, as part of the senescence-associated secretory phenotype (SASP). Cellular senescence is functionally associated with many biological processes including aging, tumor suppression, placental biology, embryonic development, and wound healing.
Class
Cellular Processes; Cell growth and death
BRITE hierarchy
Pathway map
Ortholog table
Drug
D01583 Pirfenidone (JAN/USAN/INN)
D05480 Pimecrolimus (JAN/USAN/INN)
D09033 Voclosporin (JAN/USAN/INN)
D11787 Ceralasertib (USAN/INN)
D12181 Edasalonexent (USAN/INN)
Other DBs
Organism
Homo sapiens (human) [GN:
hsa ]
Gene
7040 TGFB1; transforming growth factor beta 1 [KO:K13375 ]
7042 TGFB2; transforming growth factor beta 2 [KO:K13376 ]
7043 TGFB3; transforming growth factor beta 3 [KO:K13377 ]
1030 CDKN2B; cyclin dependent kinase inhibitor 2B [KO:K04685 ]
5925 RB1; RB transcriptional corepressor 1 [KO:K06618 ]
5933 RBL1; RB transcriptional corepressor like 1 [KO:K04681 ]
5934 RBL2; RB transcriptional corepressor like 2 [KO:K16332 ]
5290 PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922 ] [EC:2.7.1.153 ]
5293 PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922 ] [EC:2.7.1.153 ]
5291 PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922 ] [EC:2.7.1.153 ]
5295 PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649 ]
5296 PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649 ]
8503 PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649 ]
1026 CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625 ]
3105 HLA-A; major histocompatibility complex, class I, A [KO:K06751 ]
3106 HLA-B; major histocompatibility complex, class I, B [KO:K06751 ]
3107 HLA-C; major histocompatibility complex, class I, C [KO:K06751 ]
3134 HLA-F; major histocompatibility complex, class I, F [KO:K06751 ]
3135 HLA-G; major histocompatibility complex, class I, G [KO:K06751 ]
3133 HLA-E; major histocompatibility complex, class I, E [KO:K06751 ]
3805 KIR2DL4; killer cell immunoglobulin like receptor, two Ig domains and long cytoplasmic tail 4 [KO:K24231 ]
3845 KRAS; KRAS proto-oncogene, GTPase [KO:K07827 ]
4893 NRAS; NRAS proto-oncogene, GTPase [KO:K07828 ]
3265 HRAS; HRas proto-oncogene, GTPase [KO:K02833 ]
6009 RHEB; Ras homolog, mTORC1 binding [KO:K07208 ]
286826 LIN9; lin-9 DREAM MuvB core complex component [KO:K21773 ]
55957 LIN37; lin-37 DREAM MuvB core complex component [KO:K21774 ]
91750 LIN52; lin-52 DREAM MuvB core complex component [KO:K21775 ]
132660 LIN54; lin-54 DREAM MuvB core complex component [KO:K21776 ]
5928 RBBP4; RB binding protein 4, chromatin remodeling factor [KO:K10752 ]
4609 MYC; MYC proto-oncogene, bHLH transcription factor [KO:K04377 ]
1029 CDKN2A; cyclin dependent kinase inhibitor 2A [KO:K06621 ]
83593 RASSF5; Ras association domain family member 5 [KO:K08015 ]
8945 BTRC; beta-transducin repeat containing E3 ubiquitin protein ligase [KO:K03362 ]
23291 FBXW11; F-box and WD repeat domain containing 11 [KO:K03362 ]
2113 ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678 ]
1647 GADD45A; growth arrest and DNA damage inducible alpha [KO:K04402 ]
4616 GADD45B; growth arrest and DNA damage inducible beta [KO:K04402 ]
10912 GADD45G; growth arrest and DNA damage inducible gamma [KO:K04402 ]
4361 MRE11; MRE11 homolog, double strand break repair nuclease [KO:K10865 ]
10111 RAD50; RAD50 double strand break repair protein [KO:K10866 ] [EC:3.6.-.-]
3364 HUS1; HUS1 checkpoint clamp component [KO:K10903 ]
10758 TRAF3IP2; TRAF3 interacting protein 2 [KO:K21124 ]
4790 NFKB1; nuclear factor kappa B subunit 1 [KO:K02580 ]
5970 RELA; RELA proto-oncogene, NF-kB subunit [KO:K04735 ]
3576 CXCL8; C-X-C motif chemokine ligand 8 [KO:K10030 ]
3486 IGFBP3; insulin like growth factor binding protein 3 [KO:K10138 ]
5054 SERPINE1; serpin family E member 1 [KO:K03982 ]
1978 EIF4EBP1; eukaryotic translation initiation factor 4E binding protein 1 [KO:K07205 ]
677 ZFP36L1; ZFP36 ring finger protein like 1 [KO:K18753 ]
678 ZFP36L2; ZFP36 ring finger protein like 2 [KO:K18753 ]
776 CACNA1D; calcium voltage-gated channel subunit alpha1 D [KO:K04851 ]
59341 TRPV4; transient receptor potential cation channel subfamily V member 4 [KO:K04973 ]
54822 TRPM7; transient receptor potential cation channel subfamily M member 7 [KO:K04982 ] [EC:2.7.11.1 ]
5534 PPP3R1; protein phosphatase 3 regulatory subunit B, alpha [KO:K06268 ]
5535 PPP3R2; protein phosphatase 3 regulatory subunit B, beta [KO:K06268 ]
4772 NFATC1; nuclear factor of activated T cells 1 [KO:K04446 ]
4773 NFATC2; nuclear factor of activated T cells 2 [KO:K17332 ]
4775 NFATC3; nuclear factor of activated T cells 3 [KO:K17333 ]
4776 NFATC4; nuclear factor of activated T cells 4 [KO:K17334 ]
3708 ITPR1; inositol 1,4,5-trisphosphate receptor type 1 [KO:K04958 ]
3709 ITPR2; inositol 1,4,5-trisphosphate receptor type 2 [KO:K04959 ]
3710 ITPR3; inositol 1,4,5-trisphosphate receptor type 3 [KO:K04960 ]
291 SLC25A4; solute carrier family 25 member 4 [KO:K05863 ]
292 SLC25A5; solute carrier family 25 member 5 [KO:K05863 ]
293 SLC25A6; solute carrier family 25 member 6 [KO:K05863 ]
83447 SLC25A31; solute carrier family 25 member 31 [KO:K05863 ]
7416 VDAC1; voltage dependent anion channel 1 [KO:K05862 ]
7417 VDAC2; voltage dependent anion channel 2 [KO:K15040 ]
7419 VDAC3; voltage dependent anion channel 3 [KO:K15041 ]
Compound
C05981 Phosphatidylinositol-3,4,5-trisphosphate
Reference
Authors
Munoz-Espin D, Serrano M
Title
Cellular senescence: from physiology to pathology.
Journal
Reference
Authors
Childs BG, Durik M, Baker DJ, van Deursen JM
Title
Cellular senescence in aging and age-related disease: from mechanisms to therapy.
Journal
Reference
Authors
Sharpless NE, Sherr CJ
Title
Forging a signature of in vivo senescence.
Journal
Reference
Authors
Fridlyanskaya I, Alekseenko L, Nikolsky N
Title
Senescence as a general cellular response to stress: A mini-review.
Journal
Reference
Authors
Lujambio A
Title
To clear, or not to clear (senescent cells)? That is the question.
Journal
Reference
Authors
Di Mitri D, Alimonti A
Title
Non-Cell-Autonomous Regulation of Cellular Senescence in Cancer.
Journal
Reference
Authors
Francica P, Aebersold DM, Medova M
Title
Senescence as biologic endpoint following pharmacological targeting of receptor tyrosine kinases in cancer.
Journal
Reference
Authors
Bartling B
Title
Cellular senescence in normal and premature lung aging.
Journal
Reference
Authors
Munoz-Espin D, Canamero M, Maraver A, Gomez-Lopez G, Contreras J, Murillo-Cuesta S, Rodriguez-Baeza A, Varela-Nieto I, Ruberte J, Collado M, Serrano M
Title
Programmed cell senescence during mammalian embryonic development.
Journal
Reference
Authors
Herranz N, Gallage S, Gil J
Title
TORn about SASP regulation.
Journal
Reference
Authors
Martin N, Bernard D
Title
Calcium signaling and cellular senescence.
Journal
Reference
Authors
Farfariello V, Iamshanova O, Germain E, Fliniaux I, Prevarskaya N
Title
Calcium homeostasis in cancer: A focus on senescence.
Journal
Reference
Authors
McCarthy DA, Clark RR, Bartling TR, Trebak M, Melendez JA
Title
Redox control of the senescence regulator interleukin-1alpha and the secretory phenotype.
Journal
Reference
Authors
Donninger H, Schmidt ML, Mezzanotte J, Barnoud T, Clark GJ
Title
Ras signaling through RASSF proteins.
Journal
Reference
Authors
Barnoud T, Schmidt ML, Donninger H, Clark GJ
Title
The role of the NORE1A tumor suppressor in Oncogene-Induced Senescence.
Journal
Reference
Authors
Kang C, Xu Q, Martin TD, Li MZ, Demaria M, Aron L, Lu T, Yankner BA, Campisi J, Elledge SJ
Title
The DNA damage response induces inflammation and senescence by inhibiting autophagy of GATA4.
Journal
Reference
Authors
Cao X, Li M
Title
A New Pathway for Senescence Regulation.
Journal
Reference
Authors
Gire V, Dulic V
Title
Senescence from G2 arrest, revisited.
Journal
Reference
Authors
Mowla SN, Lam EW, Jat PS
Title
Cellular senescence and aging: the role of B-MYB.
Journal
Reference
Authors
Yao H, Chung S, Hwang JW, Rajendrasozhan S, Sundar IK, Dean DA, McBurney MW, Guarente L, Gu W, Ronty M, Kinnula VL, Rahman I
Title
SIRT1 protects against emphysema via FOXO3-mediated reduction of premature senescence in mice.
Journal
Reference
Authors
Hwang JW, Yao H, Caito S, Sundar IK, Rahman I
Title
Redox regulation of SIRT1 in inflammation and cellular senescence.
Journal
Related pathway
KO pathway
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