Cellular stress responses for monitoring and modulating ageing

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  • Dino Demirovic, Danmark
  • Sylvianne Schnebert, LVMH Research, St. Jean de Braye, France, Frankrig
  • Carine Nizard, LVMH Research, St. Jean de Braye, France, Frankrig
  • Suresh Rattan
Cellular stress response is a crucial factor in maintaining
efficient homeodynamics for survival, health and longevity. Both
the immediate and delayed responses to external and internal
stressors effectively determine the molecular biochemical and
physiological stability in a dynamic and interactive manner.
There are three main aspects of stress responses: (i) immediate
stress response involving extra- and intra-cellular signaling
during the period of disturbance and exposure to the stressors;
(ii) delayed stress response involving sensors and modulators in
the presence of stressors or after the removal of the stressors; and
(iii) down-stream effectors for counteracting the effects of disturbance
and for re-establishing homeodynamics. At the present it
is not known how these three steps are maintained interactively in
terms of kinetics and intensity, and how these may alter during
growth, development and ageing.
Our aim is to define and establish the immediate and delayed
stress profiles of normal human skin fibroblasts undergoing ageing
in vitro. This is done efficiently by using various cellular, molecular
and antibody-based detection methods, combined with functional
assays, such as wound healing in vitro by fibroblasts, and induction
of differentiation of telomerase-immortalised stem cells. Furthermore,
immediate and delayed stress profiles need to be established
at several age points during the replicative senescence of
cells in culture, which can then be the basis for testing potential
protectors and stimulators of homeodynamics, and create a kind of
“gold-standard” for monitoring the efficacy of other potential antiageing
and pro-survival natural and synthetic compounds.
We have so far standardised an effective method for detecting
all seven stress response pathways, by several biochemical methods,
detecting one or more proteins exclusively involved in the
specific stress response pathways. The results indicate that the ageing phenotype is a result of an ineffective probability for cells
to respond to stress.
TidsskriftFree Radical Biology & Medicine
Sider (fra-til)1
StatusUdgivet - sep. 2013

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