Control of cell replication during aging

Interdiscip Top Gerontol. 2014;39:24-44. doi: 10.1159/000358898. Epub 2014 May 13.

Abstract

The observation that human fibroblasts have a limited number of cell population doublings in vitro led to the proposal that it is the expression of cellular aging. In vitro, the proliferation of human fibroblasts terminates with a postmitotic cell which was called senescent cell. Due to misinterpreted experiments, the latter was considered the hallmark of cellular aging, although obviously we do not age because our cells stop dividing. The so-called senescent cell has been the core of the investigation on cellular aging and of the theories proposed on the subject. The search for mechanisms responsible for the postmitotic state led to contradictory results, which accumulated when the term cell senescence was used to define the growth arrest due to a variety of causes. The mechanisms believed to be causing these multiple forms of cell senescence multiplied accordingly. This was disregarded claiming that there are multiple pathways to cell senescence. Since it was thought that aging favors malignant transformation, speculations were made to find a relationship between 'cell senescence' and cancers, which led to several paradoxes. The contradictions and paradoxes should be cleared to reestablish logic and order in the field and understand its relevance for human aging.

Publication types

  • Review

MeSH terms

  • Animals
  • Cell Division / physiology
  • Cell Proliferation / physiology*
  • Cell Transformation, Neoplastic
  • Cellular Senescence / physiology*
  • Fibroblasts / physiology
  • Humans
  • Telomere Shortening / physiology