The pathway of cell senescence: WI-38 cells arrest in late G1 and are unable to traverse the cell cycle from a true G0 state

Robert Pignolo, Bernard G. Martin, Joseph H. Horton, Anne N. Kalbach, Vincent J. Cristofalo

Research output: Contribution to journalReview article

35 Citations (Scopus)

Abstract

Senescent human diploid fibroblasts have an undefined arrest state partially characterized by the differential expression of cell cycle- regulated genes and a failure to complete the mitogen-stimulated cascade of signalling events that lead to DNA synthesis. We present evidence that this arrest state precludes the entry of senescent fibroblasts into a normally reversible G0 or quiescent state. Both nuclear association kinetics and quinacrine dihydrochloride nuclear fluorescence show chromatin condensation patterns consistent with arrest in late G1 and exclusion of senescent cells from the G0 phase of the cell cycle. Steady-state thymidine kinase mRNA levels indicate that some of the signalling cascades initiated from a functional G0 state may be intact in senescent cells, at least qualitatively, and that this expression may represent an abortive attempt to complete pathways required for DNA replication. Taken together, the evidence suggests that growth arrest in senescent cells likely occurs in a physiologic state fundamentally distinct from that of the G0, quiescent state that is achieved by nonproliferating young cells. A full response to serum or growth factor addition, leading from quiescence to DNA synthesis, may require cells to initiate this traverse from a true G0 state. If so, senescent cells would be excluded from this pathway.

Original languageEnglish (US)
Pages (from-to)67-80
Number of pages14
JournalExperimental Gerontology
Volume33
Issue number1-2
DOIs
StatePublished - Jan 1 1998
Externally publishedYes

Fingerprint

Cell Aging
Cell Cycle
Cells
Fibroblasts
DNA
Quinacrine
Thymidine Kinase
Mitogens
Chromatin
Condensation
Intercellular Signaling Peptides and Proteins
Genes
Fluorescence
Association reactions
cdc Genes
Cell Cycle Resting Phase
Messenger RNA
Kinetics
Diploidy
DNA Replication

Keywords

  • Cell cycle
  • Fibroblast
  • G
  • Senescence
  • Thymidine kinase

ASJC Scopus subject areas

  • Biochemistry
  • Aging
  • Molecular Biology
  • Genetics
  • Endocrinology
  • Cell Biology

Cite this

The pathway of cell senescence : WI-38 cells arrest in late G1 and are unable to traverse the cell cycle from a true G0 state. / Pignolo, Robert; Martin, Bernard G.; Horton, Joseph H.; Kalbach, Anne N.; Cristofalo, Vincent J.

In: Experimental Gerontology, Vol. 33, No. 1-2, 01.01.1998, p. 67-80.

Research output: Contribution to journalReview article

Pignolo, Robert ; Martin, Bernard G. ; Horton, Joseph H. ; Kalbach, Anne N. ; Cristofalo, Vincent J. / The pathway of cell senescence : WI-38 cells arrest in late G1 and are unable to traverse the cell cycle from a true G0 state. In: Experimental Gerontology. 1998 ; Vol. 33, No. 1-2. pp. 67-80.
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