, Volume 6, Issue 1, pp 39–47 | Cite as

Testing the “garbage” accumulation theory of ageing: mitotic activity protects cells from death induced by inhibition of autophagy

  • Yuri StroikinEmail author
  • Helge Dalen
  • Ulf T. Brunk
  • Alexei Terman
Research article


Imperfect autophagic degradation of oxidatively damaged macromolecules and organelles (so-called biological “garbage”) is considered an important contributor to ageing and consequent death of postmitotic (non-dividing) cells, such as neurons and cardiac myocytes. In contrast, proliferating cells apparently escape senescence by a continuous dilution and repair of damaged structures during division. Postmitotic ageing can be mimicked and studied in cultures of potentially dividing cells if their mitotic activity is inhibited. To test the “garbage accumulation” theory of ageing, we compared survival of density-dependent growth-arrested (confluent) and proliferating human fibroblasts and astrocytes following inhibition of autophagic sequestration with 3-methyladenine (3MA). Exposure of confluent fibroblast cultures to 3MA for two weeks resulted in a significantly increased proportion of dying cells compared to both untreated confluent cultures and dividing cells with 3MA-inhibited autophagy. Similar results were obtained when autophagic degradation was suppressed by the protease inhibitor leupeptin. In 3MA- or leupeptin-exposed cultures, dying cells were overloaded with undegraded autofluorescent material. The results support a key role of biological lysosomal “garbage” accumulation in the triggering of ageing and death of postmitotic cells, as well as the anti-ageing role of cell division.


ageing apoptosis astrocytes autophagocytosis fibroblasts 3-methyladenine leupeptin mitosis 


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Copyright information

© Springer 2005

Authors and Affiliations

  • Yuri Stroikin
    • 1
    Email author
  • Helge Dalen
    • 1
  • Ulf T. Brunk
    • 2
  • Alexei Terman
    • 1
  1. 1.Division of Experimental Pathology II Faculty of Health SciencesLinköping UniversityLinköpingSweden
  2. 2.Department of Pharmacology, Faculty of Health SciencesLinköping UniversityLinköpingSweden

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