Long-term quiescent fibroblast cells transit into senescence.

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...

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Main Authors: Shiva Marthandan, Steffen Priebe, Peter Hemmerich, Karolin Klement, Stephan Diekmann
Format: Article
Language:English
Published: Public Library of Science (PLoS) 2014-01-01
Series:PLoS ONE
Online Access:https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115597&type=printable
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author Shiva Marthandan
Steffen Priebe
Peter Hemmerich
Karolin Klement
Stephan Diekmann
author_facet Shiva Marthandan
Steffen Priebe
Peter Hemmerich
Karolin Klement
Stephan Diekmann
author_sort Shiva Marthandan
collection DOAJ
description 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.
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spelling doaj.art-a3e83f32046b4ed7b249daf8909134532025-02-23T05:33:11ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-01912e11559710.1371/journal.pone.0115597Long-term quiescent fibroblast cells transit into senescence.Shiva MarthandanSteffen PriebePeter HemmerichKarolin KlementStephan DiekmannCellular 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.https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115597&type=printable
spellingShingle Shiva Marthandan
Steffen Priebe
Peter Hemmerich
Karolin Klement
Stephan Diekmann
Long-term quiescent fibroblast cells transit into senescence.
PLoS ONE
title Long-term quiescent fibroblast cells transit into senescence.
title_full Long-term quiescent fibroblast cells transit into senescence.
title_fullStr Long-term quiescent fibroblast cells transit into senescence.
title_full_unstemmed Long-term quiescent fibroblast cells transit into senescence.
title_short Long-term quiescent fibroblast cells transit into senescence.
title_sort long term quiescent fibroblast cells transit into senescence
url https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0115597&type=printable
work_keys_str_mv AT shivamarthandan longtermquiescentfibroblastcellstransitintosenescence
AT steffenpriebe longtermquiescentfibroblastcellstransitintosenescence
AT peterhemmerich longtermquiescentfibroblastcellstransitintosenescence
AT karolinklement longtermquiescentfibroblastcellstransitintosenescence
AT stephandiekmann longtermquiescentfibroblastcellstransitintosenescence