1. Advanced Glycation End Products (AGEs) and scar formation
A systematic review
Lennert Van Putte¹, Sofie De Schrijver¹, Peter Moortgat²
¹ University of Antwerp, Faculty of Medicine and Health science, Antwerp, Belgium
² Oscare, Organisation for Burns, Scar After-care and Research, Antwerp, Belgium

2. Conflicts of Interest
None declared

3. 1. AGEs = Advanced Glycation End Products
Collective term for all degenerated protein/lipid/nucleic acid molecules, damaged because of anchored sugar molecules
Formed by multiple reactions
Role in aging and age-related complications
Best known AGE = HbA1c
Skin relevant AGE = Collagen

4. 2. AGEs: Formation Sugars Oxidative stress Time IRREVERSIBLE AGEs
Figure: Khera PK, Joiner CH, Carruthers A, et al: Evidence for interindividual heterogeneity in the glucose gradient across the human red blood cell membrane and its relationship to hemoglobin glycation. Diabetes 2008 Sep;57(9):
Sugars
Oxidative stress
Time

5. And you, how AGE’d are you?

6. 3. AGEs: Glycation Targets
When & where does accumulation occur?
From the age of 20 years old!
In skin, joints, skeletal & vascular muscle, glomerular basement membrane
How does accumulation occur?
Balance between formation and removal
Formation: Exogenous (ingestion) & endogenous (DM, smoking, …)
Removal: Kidneys (GFR as indicator)
Which proteins?
Collagen
Albumin
LDL Hb

7. 4. AGEs : consequences Crosslinking collagen  Directly ↓ function
RAGE  Inflammation
 Oxidative stress
Binding lipoproteins  Atherosclerosis

8. 5. AGE: consequences in skin
Figure: Gkogkolou P, Böhm M. Advanced glycation end products: Key players in skin aging? Dermatoendocrinol Jul 1;4(3):

9. 6. AGEs: Skin and Wound Consequences
↓ Skin thickness
↓ Elasticity
↑ Contraction
↑ Time of inflammation
↑ Time of wound closure
! All drawn conclusions concerned studies on diabetics only !

10. 7. AGEs: scar formation in elderly
“What is the effect of AGEs on scar formation in elderly?” “What can we learn from the elderly in relation to AGEs and scarring?”
Figure: “Scar”, from the movie The Lion King, Walt Disney Pictures 1994.

11. 7. AGEs: Scar Formation in Elderly
Simple deduction…
Diabetic  ↑ AGEs in skin
Older  ↑ AGEs in skin
AGEs & diabetic wound healing ≈ AGEs & elderly wound healing?

12. 7. AGEs: Scar Formation in Elderly
But NOT simpler…
Paradoxically:
Elderly apparently heal better than younger people after cutaneous surgery
Elderly vs. Healthy adults
Faster “Normalization”
Less red
Less hypertrophic
Increased contraction
Diabetics vs. Healthy adults
Delayed wound closure
Prolonged inflammation & redness
Reduced thickness of dermis
Increased rigidity

13. Anti-AGE strategies 3. Nutriceuticals 4. Dietary measures
1. AGE Formation Inhibitors
3. Nutriceuticals
4. Dietary measures
Aminoguanidine
Ascorbic acid (vitamine C)
Caloric restriction
Pyridoxamine (isoform vitamine B)
α-tocopherol
Niacinamide
5. Targeting RAGE
Pyridoxaln
2. AGE breakers
Sodium selenite
siRNA
Dimethyl-3-phenayl-thiazolium chloride (ALT-711)
Selenium yeast
Putative small molecular inhibitors against RAGE-induced signalling
Trolox
N-phenacylthiazolium
Rivoflavin
N-phenacyl-4,5-dimethylthiazolium
Zinc
FAOXs
6. Molecular chaperones
Manganese
FN3K
Alfa lipoic acid
Carnosine
The enzymatic system of Glo

14. 8. Conclusions Abundant evidence supports:
↑ Skin AGEs in both elderly and diabetics
Pathological role of AGEs in wound healing
Effectiveness of possible therapeutic strategies
Similar trends in wound healing in both elderly and diabetics
However, some unexplained paradoxical dissimilarities
 Further research is required to conclude the definite role of AGEs in scar formation and therapy

15. 9. Future Investigations
Correlation of scar characteristics (thickness, redness, elasticity etc.) with the amount of AGEs
Anti-AGE strategies:
Diet (e.g. more antioxidants, less carbohydrates)
Antioxidant cream (e.g. Q10)
Topic Metformin (Glucophage®)
Diphtheria toxin (very experimental but promising)

16. Thank you for your attention!