title: Status of mTOR activity may phenotypically differentiate senescence and quiescence.
abstract: SA β-Gal activity is a key marker of cellular senescence. The origin of this activity is the lysosomal β-galactosidase, whose activity has increased high enough to be detected at suboptimal pH. SA β-Gal is also expressed in the cells in quiescence driven by serum-starvation or a high confluency, and it has been hypothesized that SA β-Gal positivity is rather a surrogate marker of high lysosome content or activity. In this study, it was determined how SA β-Gal activity is expressed in quiescence and how lysosome content and activities are differently maintained in senescence and quiescence using DNA damage-induced senescence and serum starvation-induced quiescence as study models. Lysosome content increased to facilitate SA β-Gal expression in both the conditions but with a big difference in the levels of the change. Lipofuscins whose accumulation leads to an increase in residual bodies also increased but with a smaller difference between the two conditions. Meanwhile, lysosome biogenesis was actively ongoing only in senescence progression, indicating that the difference in the lysosome contents may largely be due to lysosome biogenesis. Further, the cells undergoing senescence progression but not the ones in quiescence maintained high mTOR and low autophagy activities. Overall, the results indicate that, although SA β-Gal is expressed due to the elevated lysosome content in both cellular senescence and quiescence, senescence differs from quiescence with high lysosome biogenesis and low autophagy activity, and mTOR activity might be involved in these differences.
authors.affiliation: Department of Life Science, University of Seoul, Seoul 130-743, Korea.
authors.forename: Sohee
authors.initials: S
authors.lastname: Cho
authors.forename: Eun Seong
authors.initials: ES
authors.lastname: Hwang
mesh_terms: D001343:Autophagy; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000378:metabolism; D059447:Cell Cycle Checkpoints; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D016895:Culture Media, Serum-Free; D015870:Gene Expression; D005786:Gene Expression Regulation; D006801:Humans; D051907:Lysosomal Membrane Proteins / Q000235:genetics / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D010641:Phenotype; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism*; D001616:beta-Galactosidase / Q000378:metabolism
chemical_list: D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D016895:Culture Media, Serum-Free; D051907:Lysosomal Membrane Proteins; C477012:MAP1LC3A protein, human; D008869:Microtubule-Associated Proteins; C064972:TFEB protein, human; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; D001616:beta-Galactosidase