ANTI-AGEING 57
Fighting ageing in tired skin with a glacier bacterium
n Christina Pickel, Franziska Wandrey, Daniel Schmid, Bernhard Henes, Fred Zülli – Mibelle Biochemistry, Switzerland
The life cycle of proteins in our cells involves various processes, starting with the transcription from DNA and ending with their degradation. An intermediate station for the vast majority of proteins is the endoplasmic reticulum (ER), where they are correctly folded with the help of chaperone proteins in order to then continue their journey in the correct shape to fulfil their function. The ER also represents an important checkpoint for quality control, and upon accumulation of incorrectly folded proteins, a process termed unfolded protein response (UPR) is initiated to facilitate clearance of these potentially toxic proteins.1
Recent research It has
showed that expression of BiP is upregulated prior to increased expression of collagen at night when it supports cellular regeneration processes.4
further been shown that sleep deprivation affects protein folding and causes ER stress, leading to the activation of the UPR and an increase in the expression of BiP.3,5,6
This
likely helps the cell to cope with the stress and aids regeneration and repair of the cell. However, basal chaperone expression as well as the ability to activate the UPR upon sleep deprivation were shown to decrease in aged cells.3,7
This leads to the
accumulation of wrongly folded proteins, which cause further ER stress and subsequently damage the cell. Another consequence of ER stress is the formation of mitochondria-associated membrane (MAM) contact points, an interaction platform with mitochondria.8
In line, sleep
deprivation also causes a reduction of mitochondrial activity, leading to reduced energy levels as reflected by a drop in the levels of ATP, the cellular energy currency.9 This further prevents the activity of ATP- dependent chaperones upon lack of sleep, deteriorating cellular stress and causing cell damage. Taken together, sleep deprivation does not only cause a tired appearance on the macroscopic level but is also an ageing
November 2019
Figure 1: Gene expression of chaperone genes in aged fibroblasts treated with Iodobacter ssp. extract relative to untreated cells.
factor on the molecular level. Moreover, it has been shown that, similar to UV- irradiation or oxidative stress, inadequate sleep is correlated with reduced skin health, weakens the skin’s ability to repair itself at night and can accelerate skin ageing. Therefore, active ingredients for cosmetic
use which support the skin in coping with cellular stresses due to lack of sleep are desirable.
Extremophile bacteria – Masters of survival in a hostile environment Extremophile organisms are masters of
PERSONAL CARE ASIA PACIFIC 50 150 Abstract
One of the major chaperones of the ER also involved in the UPR and upregulated by cellular stress is BiP (binding immunoglobulin protein).2,3
Long working hours and a hectic lifestyle are common phenomena in today’s society. This often results in a lack of sleep, which is markedly reflected on the skin by a tired appearance of the face. Also on the molecular level, lack of sleep causes stress and leads to premature ageing. A major stress mechanism, the unfolded protein response (UPR) of the endoplasmic reticulum (ER), gets compromised by sleep deprivation, leading to the accumulation of misfolded proteins which damage the cell. Moreover, mitochondrial ATP production is impaired upon lack of sleep due to the link between ER and mitochondrial stress. To target this novel cellular ageing mechanism, an extract of the psychrotolerant Swiss glacier bacterium Iodobacter ssp. was developed and analysed for its efficacy to reduce ER stress and visible signs of tiredness. Treatment of aged fibroblasts with the extract led to an increase in the expression of ER chaperones which mediate the UPR. Moreover, Iodobacter spp. increased ATP levels in a cellular model of sleep deprivation. Placebo-controlled randomised clinical studies conducted with sleep-deprived and overworked volunteers demonstrated that treatment with the Iodobacter-derived active ingredient improved several skin parameters associated with skin ageing, leading to an energised and rejuvenated appearance.
n Control n 1% lodobacter ssp. extract 250
200
100
0 Control BiP Endoplasmin Calnexin Calreticulin
Gene expression compared to control cells (=100) in %
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