Quantitative assessment of markers for cell senescence

Conor Lawless, Chunfang Wang, Diana Jurk, Alina Merz, Thomas von Zglinicki, Joao Passos

Research output: Contribution to journalArticle

124 Citations (Scopus)

Abstract

Cellular senescence, the irreversible loss of replicative capacity, might be a tumour suppressor and a contributor to age-related loss of tissue function. The absence of quantitative tests for reliability of candidate markers for senescent cells is a major drawback in cell population studies. Fibroblasts in culture constitute mixed populations of proliferation-competent and senescent cells, with transition between these with increasing population doublings (PD). We estimated senescent fraction in human and mouse fibroblasts with high precision from easily observed growth curves using a dynamic simulation model. We also determined senescent fractions, at various PD (over a wide range of senescent cell frequencies) using candidate senescence markers: Ki67, p21 (CDKN1A), γH2AX, SAHF and Sen-β-Gal either alone or in combination, and compared with those derived from growth curves. This comparison allowed ranking of candidate markers. High rankings were obtained for Sen-β-Gal, SAHFs and the combination of Ki67 negativity with high (>5 per nucleus) γH2A.X foci density in MRC5 fibroblasts. We demonstrate that this latter marker combination, which can easily be performed in paraffin-embedded tissue, gives quantitative senescent cell frequency estimates in mouse embryonic fibroblast cultures and in mouse intestinal sections. The technique presented is a framework for quantitative assessment of markers for senescence.

Original languageEnglish (US)
Pages (from-to)772-778
Number of pages7
JournalExperimental Gerontology
Volume45
Issue number10
DOIs
StatePublished - Oct 1 2010
Externally publishedYes

Fingerprint

Cell Aging
Fibroblasts
Cell culture
Population
Tissue
Paraffin
Tumors
Growth
Cells
Computer simulation
Neoplasms

Keywords

  • Ageing
  • Bayesian inference
  • Dynamic model
  • Fibroblasts
  • Growth curves
  • Markers
  • Mathematical model
  • Population
  • Senescence
  • Simulation

ASJC Scopus subject areas

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

Cite this

Quantitative assessment of markers for cell senescence. / Lawless, Conor; Wang, Chunfang; Jurk, Diana; Merz, Alina; Zglinicki, Thomas von; Passos, Joao.

In: Experimental Gerontology, Vol. 45, No. 10, 01.10.2010, p. 772-778.

Research output: Contribution to journalArticle

Lawless, Conor ; Wang, Chunfang ; Jurk, Diana ; Merz, Alina ; Zglinicki, Thomas von ; Passos, Joao. / Quantitative assessment of markers for cell senescence. In: Experimental Gerontology. 2010 ; Vol. 45, No. 10. pp. 772-778.
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