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A cell is 'senescent' when is has permanently left the cell-cycle. This can be caused by stresses, or by reaching the 'Hayflick limit' (the cell has reached its replicative lifespan, as defined by its telomeres).

Cells cultured in vitro can be used as models to study senescence (or sometimes 'ageing', although the distinction there is not necessarily within scope of this question) by growing the same population of cells for a long time (many passages). A common method to identify a senescent cell population is to use beta-galactosidase staining.

I was wondering to what degree senescent cells in culture (identified by beta-gal staining) are actually comparable to those you might expect in vivo. I ask because it seems to me that a terminally senescent cell may not actually survive long in an organism, so what we refer to as senescent cells in vivo are actually pre-senescent cells? I haven't got any basis for this, just a feeling. (Very scientific I know).

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maybe the term you are looking for is 'apoptosis'? –  shigeta Dec 1 '12 at 17:29

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Senescence does not equal cell death, but is simply an arrested state in which the cell still remains viable (1). It has been shown throughout the literature that this state corresponds with an altered cell cycle profile different from contact inhibition or damage-induced arrest (2). This corresponds with an enlarged cell size, altered gene expression (3, 4), and the pH-dependent expression of β-galactosidase (5). This has been shown both in cultured cells and in animal models (6, 7).

  1. Goldstein, S. (1990) Science 249, 1129-1133.
  2. Sherwood, S. W. et al. (1988) Proc. Natl. Acad. Sci. , USA 85, 9086-9090.
  3. Cristofalo, V. J. et al. (1998) Crit. Rev. Eukaryot Gene Expr. 8, 43-80.
  4. Linskens, M. H. et al. (1995) Nucleic Acid Res. 23, 3244-3251.
  5. Dimri, G. et al. (1995) Proc. Natl. Acad. Sci., USA 92, 9363-9367.
  6. Swarbrick, A. et al. (2008) Proc. Natl. Acad. Sci., USA 105, 5402-7.
  7. Efeyan, A. et al. (2009) PLoS One 4, e5475.
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Hi - thanks for the info on senescent cells. So you are saying that cells senesced in culture are comparable to those in vivo? Or you are saying that they are not comparable, because senescent cells in vivo are not necessarily replicatively senesced cells? –  Luke Dec 4 '12 at 10:29
    
Cells in culture are necessarily different than those in vivo, as they are (generally) lacking the 3D structure, extra-cellular matrix, and heterogeneity found in tissues, but fundamentally senescence is the same across all cells, regardless of where they happen to be living at the moment. It is characterized by the phenotypes I mentioned above, including cell cycle arrest and replication inhibition. "Replicatively senesced" is redundant :) –  MattDMo Dec 4 '12 at 19:18
    
I wouldn't have said redundant, simply because that is what our in vivo experiment was designed to emulate - we have aged a culture of cells (human primary cell lines) by repeated passage until growth arrest (confirmed by β-galactosidase, morphological changes, and drastic slowing of doubling time). We are now using these as models of senescence in vitro. If I understand you correctly then this is a reasonable model because senescent cells tend to display quite a homogenous phenotype? So even though senescent cells in vitro may have arrived by a different route, this is still a good model? –  Luke Dec 5 '12 at 11:50
    
I can't judge your model as a whole (appropriateness of cell lines used, method of culture, etc.), but this sounds pretty good. The senescent cell phenotype is fairly homogeneous, allowing for the fact that different cell types and different cell lines can have vastly different overall phenotypes in terms of gene expression, morphology, etc., and these may be affected by the route by which senescence was arrived. The model sounds good, but keep in mind it's only a model, and you need to judge your assumptions carefully when looking at your results. –  MattDMo Dec 5 '12 at 19:28
    
Many thanks indeed for your input, and the links. –  Luke Dec 5 '12 at 22:19

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