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Skin Chronologic Aging. Which Endpoint for which model?

The skin aging process is mostly allocated to the activities of dermal fibroblasts. At BIOalternatives, we developed three different models of aged fibroblasts dedicated to aging studies and anti-age testing. Aiming at proposing the best model and analytical solutions to our customers, we performed an in depth molecular and metabolic comparative analysis of these three models:

replicative aging/senescence model (Hayflick):

obtained by successive replication cycles of a normal human dermal fibroblast pool (PF, 6 donors) : R7 (normal)/R17 (aged, not still senescent).

donor age-dependent model:

obtained by cloning dermal fibroblasts from a 22 years old donnor (F048) and from a 64 years old donor (F049) and selection regarding different metabolic parameters.

accelerated senescence model (H2O2):

obtained by H2O2 treatment of a normal human dermal fibroblast pool (PF) and 1 week subculture.

The three models have been evaluated for:

cellular morphology
alpha-SMA protein expression
proliferation
Beta-galactosidase activity
ECM protein synthesis
collagen I protein syntesis
hyaluronic acid synthesis
total GAGs synthesis
lattice contraction
MMP release
gene expression profiling

beta-galactosidase activity detection in aged dermal fibroblasts by flow cytometry and imaging

Results:

Differential biological responses of the three models of aged fibroblasts in comparison to normal fibroblasts:

Our conlusion:
Regarding the results of these molecular and metabolic analysis, the replicative aging/senescence model seems to be the best model for aging studies. The accelerated senescence model is of interest, especially in the case of a preventive treatment. The donor age-dependent model is of less value.

The most relevant endpoints for testing compounds are: