title: Long-term quiescent fibroblast cells transit into senescence.
abstract: Cellular senescence is described to be a consequence of telomere erosion during the replicative life span of primary human cells. Quiescence should therefore not contribute to cellular aging but rather extend lifespan. Here we tested this hypothesis and demonstrate that cultured long-term quiescent human fibroblasts transit into senescence due to similar cellular mechanisms with similar dynamics and with a similar maximum life span as proliferating controls, even under physiological oxygen conditions. Both, long-term quiescent and senescent fibroblasts almost completely fail to undergo apoptosis. The transition of long-term quiescent fibroblasts into senescence is also independent of HES1 which protects short-term quiescent cells from becoming senescent. Most significantly, DNA damage accumulates during senescence as well as during long-term quiescence at physiological oxygen levels. We suggest that telomere-independent, potentially maintenance driven gradual induction of cellular senescence during quiescence is a counterbalance to tumor development.
authors.affiliation: Leibniz-Institute for Age Research- Fritz Lipmann Institute, JenAge (Jena Centre for Systems Biology of Aging), Beutenbergstrasse 11, Jena, Germany.
authors.forename: Shiva
authors.initials: S
authors.lastname: Marthandan
authors.affiliation: Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute e.V. (HKI), Jena, Germany.
authors.forename: Steffen
authors.initials: S
authors.lastname: Priebe
authors.affiliation: Leibniz-Institute for Age Research- Fritz Lipmann Institute, JenAge (Jena Centre for Systems Biology of Aging), Beutenbergstrasse 11, Jena, Germany.
authors.forename: Peter
authors.initials: P
authors.lastname: Hemmerich
authors.affiliation: Leibniz-Institute for Age Research- Fritz Lipmann Institute, JenAge (Jena Centre for Systems Biology of Aging), Beutenbergstrasse 11, Jena, Germany.
authors.forename: Karolin
authors.initials: K
authors.lastname: Klement
authors.affiliation: Leibniz-Institute for Age Research- Fritz Lipmann Institute, JenAge (Jena Centre for Systems Biology of Aging), Beutenbergstrasse 11, Jena, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Diekmann
mesh_terms: D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000378:metabolism; D002455:Cell Division; D049109:Cell Proliferation; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000502:physiology*; D004249:DNA Damage; D005347:Fibroblasts / Q000166:cytology* / Q000502:physiology; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D016615:Telomere / Q000235:genetics; D000072056:Transcription Factor HES-1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D000072056:Transcription Factor HES-1; C078493:HES1 protein, human