Senescent cells

Figure 26.1 Immortalization of human cells Cells enter replicative senescence at mortality stage 1 (Ml Hayflick limit) after about 60 population doublings (PD). The protein p 16 accumulates in senescent cells. The simian virus 40 (SV40) large T antigen as well as the human papilloma virus (HPV) type 16-E6 and E7 proteins sequester the retinoblastoma protein (Rb) and/or p53 constitutively releases the transcription factor E2F. E2F induces expression proteins required for progression through Gl/S transition, thus the cells escape cell cycle arrest. At mortality stage 2 (M2), transformed cells must overcome senescence and crisis before they are immortalized. This is likely to involve the activation of telomerase either by the introduction of hTERT cDNA or by a genetic change that activates telomerase.

Total number of population doublings (PDs). The more population doublings a culture has experienced, the greater number of senescent, or possibly near-senescent cells there will be in that culture. The problem will be that a culture at a low PD number may superficially look the same as a population with a higher PD number, and be growing at the same rate, but might behave quite differently in a biocompatibility assay. 

Caron, M., et al. (2007). Human lipodystrophies Unked to mutations in A-type lamins and to HIV protease inhibitor therapy are both associated with prelamin A accumulation, oxidative stress and premature cellular senescence. Cell Death Differ 14 1759-1767. 

Rontani F.-F., Cuny P., Gossi V., and Beker B. (1997) Stability of long-chain alkenones in senescing cells of Emiliania huxleyr. effect of photochemical and aerobic microbial degradation on the alkenone unsaturation ratio (Ufv). Org. Geochem. 26, 503-509. 

U. Ponappan et al. Decreased proteasome-mediated degradation in T cells from the elderly a role in immune senescence, Cell Immunol. 192 (1999) 167-174. 

For most of the G4 ligands studied so far, apoptotic cell death could be achieved after several cell cycles in tumor-derived cell lines. The triazine ligand 12459 activates the mitochondrial cell death pathway through alteration of the Bax/Bcl-2 balance, which leads to caspase 3 activation. At short-term, it could be noticed that apoptosis predominates over the appearance of senescent cells for this ligand. ... 

Maarten H. K. Linskens, Junli Feng, William H. Andrews, Brett E. Enlow, Shahin M. Saati, Leath A. Tonkin, Walter D. Eunk, Bryant Villeponteau, Cataloging altered gene expression in young and senescent cells using enhanced differential display. Nucleic Acids Research, 23 (1995), 3244-3251. 

Afshari, C.A. and Barrett, J.C., Disruption of Gg-Gj arrest in quiescent and senescent cells treated with phosphatase inhibitors. Cancer Res., 54, 2317, 1994. 

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