In chimeric mice, where half of the cells have exogenous LacZ gene (LZ +), we use β-gal staining to detect the population of the cells that are LZ+. How can we be sure that these cells are actually getting stained because they are LZ+ and not because the cells are senescent?
Hah that's an entertaining problem. It depends a little bit on the context of how you analyze them. Is that a histology staining experiment? Flow cytometry? Live culture? Are your mice old?
If you can work with live cells in bulk, you could look at the secretory phenotype. High baseline IL6 secretion would be a marker that's frequently used for senescence. qPCR would be fine too.
If you need to do it on a cell-by-cell basis, it's not as clear. There's no surface marker or "other" histological stain for senescence known. Sometimes you can tell by size -- senescent cells can be huge, and have many lysosomes (a potential reason for their high natural bgal level). But that's considered less specific than the stain, and depends on your cell type of interest. There can also be differences in staining intensity. Natural senescence bGal would be weaker than your transgene. But that's merely a quantitative difference, and probably awkward to work with.
It would be easiest to work with young mice, where senescent cell numbers are very low. Even in old mice, they should be low enough. Nowhere near 50%. I think it should be fine to confirm that in the parental generation once, do a young vs old baseline study. This should confirm that the senescent cell numbers are orders of magnitude below where you would need to worry about them.
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