Glycation during human dermal intrinsic and actinic ageing: an in vivo and in vitro model study.
BACKGROUND
Non-enzymatic glycation occurring in normal human skin plays an important part in ageing. OBJECTIVES To visualize and quantify, in human subjects, the extent of glycation during human dermal intrinsic and actinic ageing, and to develop a reliable reproducible in vitro model for evaluating the efficacy of potential inhibitors of glycation.


METHODS
By immunohistochemistry using a monoclonal antibody recognizing carboxymethyl lysine, an advanced glycation end-product (AGE) (first objective), and by incubating dead de-epidermized dermis (DED) with glucose to simulate ageing-induced glycation in a human dermal equivalent model (second objective).


RESULTS
We found that glycation of the dermis generally arises after 35 years, then increases rapidly with intrinsic ageing. We also noticed an enhancement of glycation by solar irradiation that occurred via glycation of the elastic fibre network or solar elastosis tissue. In the model, production of AGEs appeared in a time-dependent way, mimicking glycation observed in vivo during chronological ageing. Irradiation of DED before incubation with glucose strongly enhanced induction of AGEs, corresponding to the effect of solar irradiation on AGEs observed in vivo.


CONCLUSIONS
These results confirm a marked increase of AGEs during intrinsic ageing in normal human skin and also suggest that glycation is enhanced in photoaged skin.
Jeanmaire
C
C
Laboratoires Sérobiologiques, Division de COGNIS France, Département Recherche et Développement, 5--7 rue de Seichamps, 54425 Pulnoy, France. Christine.jeanmarie@cognis.com
Danoux
L
L
Pauly
G
G
D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005455:Fluorescent Antibody Technique; D006031:Glycosylation / Q000187:drug effects; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D008875:Middle Aged; D011506:Proteins / Q000378:metabolism; D015595:Skin Aging / Q000187:drug effects / Q000502:physiology*; D044465:White People
D006146:Guanidines; D011506:Proteins; C004479:pimagedine