Is senescence-associated β-galactosidase a marker of neuronal senescence?

One of the features of cellular senescence is the activity of senescence-associated- beta-galactosidase (SA-beta-gal). The main purpose of this study was to evaluate this marker of senescence in aging neurons. We found that cortical neurons exhibited noticeable SA-beta-gal activity quite early in culture. Many SA-beta-gal-positive neurons were negative for another canonical marker of senescence, namely, double-strand DNA breaks (DSBs). Moreover, DDR signalling triggered by low doses of doxorubicin did not accelerate the appearance of neuronal SA-beta-gal. In vivo, we observed pronounced induction of SA-beta-gal activity in the hippocampus of 24-month-old mice, which is consistent with previous findings and supports the view that at this advanced age neurons developed a senescence-like phenotype. Surprisingly however, relatively high SA-beta-gal activity, probably unrelated to the senescence process, was also observed in much younger, 3-month-old mice. In conclusion, we propose that SA-beta-gal activity in neurons cannot be attributed uniquely to cell senescence either in vitro or in vivo. Additionally, we showed induction of REST protein in aging neurons in long-term culture and we propose that REST could be a marker of neuronal senescence in vitro.