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Table 1. Summary of studies supporting a protective role for Edafence against exposome agents
Exposome agent Experimental model EDA Concentrations Phenotypes improved by EDA Ref.
In vitro H 2 O 2 /oxidative stress in vitro 0.3-1 mg/mL *Viability [78]
(HF) *Senescence (β-galactosidase, Sirt1,
LmnC)
*Proliferation [cytometry, proliferating
cell nuclear antigen (PCNA)]
*Antioxidant response (Trx2)
Osmotic stress in vitro 0.3-1 mg/mL *Viability [75]
(HF)
Thermal stress in vitro 2.5 mg/mL *Viability [75]
(heat and cold) (HaCaT) *Mitochondrial potential and corrected
mitochondrial potential
Natural aging in vitro 0.9 mg/mL *Telomere length [84]
(Keratinocytes)
Tobacco (5%) in vitro 5-10 mg/mL *Viability [81]
Urban pollution: (HF) *Cell morphology
Cr (III y VI) 6 mcg;
Cd 3 mcg y As 9 mmol/L
Urban pollution: in vitro 0.1-0.3 mg/mL *Viability & cell morphology [79]
Dioxin (TCDD, 10 nmol/L)/ (HF, HaCaT) *DDR (γH2AX, PARP)
2
UVA (3000 mJ/cm ) & *Stress/apoptotic signaling (caspase
2
UVB (300 y 700 mJ/cm ) 3, survivin, autophagy (LC3B), AhR)
*Tissue remodeling (MMP1, loricrin)
Dioxins 10 nmol/L Human Skin organ 2.5 mg/mL *Tissue architecture and integrity [80]
Urban pollution Culture *Viability
(As 9 mmol/L, Cr VI 0.5 *Apoptosis
mmol/L)
Visible light in vitro 0.1-0.5 mg/mL *Viability & cell morphology [82]
(400-730 nm) (HF, HaCaT) *DDR (γH2AX, PARP)
Infrared *Stress/apoptotic signaling
(550-1400 nm) [caspase-3, survivin, autophagy
(LC3B), AhR]
*Tissue remodeling (MMP1, loricrin,
collagen I, elastin)
Blue light in vitro 0.1 mg/mL *Viability [83]
(HF, Melanocytes) *ROS levels
*Mitochondrial integrity (architecture
and membrane potential)
*Melanization
In vivo Facial Photoaging Commercial compound *Viscoelasticity & firmness [89]
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(age 45-65 year) (EDAFENCE , (Cutometer )
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RetinSphere, *Wrinkles (Visia & Visioline )
Niacinamide)
Urban pollution Commercial compound *Barrier function (TEWL) [87]
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(In winter; age 35-45 year) (EDAFENCE , SCA , *Antioxidant effect (SQOOH/SQ)
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vitamin C, ferulic acid) *Remove dark spot (Colorimeter )
Urban pollution Commercial compound *Barrier function [88]
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(In summer; age 35-45 (EDAFENCE , SCA , (TEWL & Corneometry)
year) vitamin C, ferulic acid) *Antioxidant effect (SQOOH/SQ)
DDR: DNA damage response; γH2AX: phosphorylated H2A histone family member X; PARP: poly-ADP ribose polymerase; TEWL:
transepidermal water loss
activity and, most importantly, on the translation of those promising in vitro and ex vivo findings to the
effects attainable in vivo.
DECLARATIONS
Acknowledgments
Miguel Sánchez-Álvarez provided support for manuscript preparation and editing.

Authors’ contributions
Substantially contributed to the conception and design of the review: Pérez-Davó A
Organized and performed meta-analysis across in vivo and in vitro Edafence® studies: Mataix M,