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Title: Anti-stress gene response in cell and tissue ageing : role of transcription factor NF-E2-related factor-2 and effect of dietary activators
Author: Hariton, Florence A. G.
ISNI:       0000 0004 5349 4876
Awarding Body: University of Warwick
Current Institution: University of Warwick
Date of Award: 2014
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The concept of cellular senescence is based on the notion that proliferation of normal diploid cells can only occur for a limited period of time after which cells slowly cease to divide and die. This limitation of lifespan for in vitro cell cultures was first described by Leonard Hayflick in 1961, going against the theory formulated by Alexis Carrel claiming that cells kept in culture have an unlimited potential for division (Carrel and Ebeling, 1921). Evidence from cell senescence studies have been used to explain the basis of healthy ageing as well as develop food supplements promoting the delay of ageing. Since these discoveries, there has been marked expansion of anti-stress gene response research with relation to the role of the transcription factor NF-E2-related factor-2 as well as healthy ageing with regards to dietary activators intake. This study examined the effects of sulforaphane (SFN) and hesperetin (HESP) on MRC-5 cell senescence in vitro as well as characterized gene expression and cell metabolism in cells escaping senescence by treatment with SFN and HESP and the mechanism of decrease glucose metabolism by SFN and HESP action linked to delay of fibroblast senescence. The effects of treatment of MRC-5 with the dietary bioactivators SFN and HESP was studied and shown to delay cellular senescence in these cells in vitro. Similar findings for SFN treatment of BJ cells were found previously by studies of the host team. Caloric restriction mimetic mechanisms by treatment with 1 μM SFN and 5 μM HESP was shown due to the decrease in culture glucose consumption increase with senescence in these treatment groups and this CR restriction mimetic effect and decrease in the flux of formation of D- and L-lactate in the SFN-treated group was consistent with previous studies done in CR and ageing in mice models (Hargopan, Ramsey and Weindruch, 2003). Moreover, in this study, SFN was shown to act as a CRM dietary bioactive through cellular contents of glycolytic intermediates with SFN-treatment (Bensaad et al., 2006). Finally, the mechanism by which SFN induces delay of senescence through CR was shown to be due to the extraction of Mondo A from the cell nucleus to the cytoplasm.
Supervisor: Not available Sponsor: Unilever (Firm) ; Biotechnology and Biological Sciences Research Council (Great Britain)
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH Natural history