Aging and photoaging affect gene expression in cultured human keratinocytes.
BACKGROUND
Aging has two components: changes that occur in all individuals with the passage of time alone and changes that occur to varying degrees in different individuals as a result of repeated environmental injury. In the skin, the major environmental influence is sun exposure, and the combined effect of aging and sun damage has been termed photoaging. To determine whether aging and photoaging have characteristic effects on gene expression, we performed Northern blot analysis of several genes in early-passage cultured keratinocytes derived from donors of different ages (newborn, young adult, and old adult) and from paired sun-exposed (photoaged) and sun-protected sites of old-adult donors.


METHODS
We examined genes involved in cell division, immunomodulation, or differentiation. Aging alone strikingly increased the baseline expression of the differentiation-associated SPR2 and interleukin 1 receptor antagonist (IL-1ra) genes but had relatively little effect on the UV inducibility of any genes studied. In contrast, photoaging markedly increased the inducibility of the c-fos proto-oncogene and decreased the baseline expression of SPR2 and IL-1ra relative to that in cells derived from sun-protected skin of the same donors.


CONCLUSIONS
Both aging and photoaging alter the expression of selected genes that are implicated in growth, differentiation, immunomodulation, and UV response in human epidermis. This may explain, in part, the predisposition to photocarcinogenesis in chronically sun-exposed skin of older individuals.
Gilchrest
B A
BA
Department of Dermatology, Boston University School of Medicine, Mass.
Garmyn
M
M
Yaar
M
M
D000328:Adult; D000368:Aged; D000375:Aging / Q000235:genetics*; D002478:Cells, Cultured; D005786:Gene Expression Regulation / Q000528:radiation effects*; D016762:Genes, fos / Q000235:genetics; D006801:Humans; D007231:Infant, Newborn; D015603:Keratinocytes / Q000502:physiology* / Q000528:radiation effects*; D000090063:Proto-Oncogene Mas; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors / Q000235:genetics; D015595:Skin Aging / Q000235:genetics*; D014466:Ultraviolet Rays
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D017472:Receptors, Interleukin-1