Skin aging vs. photoaging: Gene expression profiles drive treatment approaches

June 1, 2008

Research at the gene expression level indicates that targeting the immune/inflammatory response could prove an effective approach in battling both intrinsic aging and photoaging, says a study co-author.

Key Points

National report - A recent study comparing the impact of sun protection and sun exposure on gene expression in the skin of young and aged women shows that the immune/inflammatory response is a dominant theme in both chronologic aging and photoaging.

The broad range of gene expression changes that researchers found suggests that multi-ingredient antiaging skincare products will likely work better than single-agent products, a study co-author says.

A small but growing number of studies have analyzed skin aging at the whole-genome expression level, says Michael K. Robinson, Ph.D., principal scientist, global biotechnology, with Cincinnati-based Procter & Gamble Beauty.

Sample population

In designing the study, Dr. Robinson says, "We wanted to look at the phenomena of intrinsic aging, as well as the effects of photodamage, in the same experiment, so we could do various comparisons."

To that end, researchers obtained biopsies from UV-exposed outer forearm skin and UV-protected buttock skin from 20 female subjects - 10 aged 18 to 20 years and 10 aged 60 to 67 years (the latter with moderate to severe photodamage). This yielded four different types of samples: Young buttock (YB), young arm (YA), old buttock (OB) and old arm (OA).

From these samples, investigators hybridized target cRNA (prepared from extracted total RNA) to U133 Plus 2 GeneChip microarrays (Affymetrix), each of which essentially represents the entire human genome through more than 54,000 separate probe sets, Dr. Robinson tells Dermatology Times.

Probe sets

"Probe sets are simply collections of short DNA sequences complementary to parts of an mRNA sequence. For certain genes, there may be multiple probe sets that sample that message a little differently," he says.

Next, researchers filtered statistically analyzed data by significance (p<0.05) and fold changes.

Each probe set yields a numerical value, he says, "and a fold change refers to the difference in expression of a probe set between one condition and another, expressed as a ratio."

A 1.5-fold change, for example, means gene expression must be at least 50 percent higher or lower in one sample population than the other, Dr. Robinson says.

Heat maps allowed researchers to represent upregulated genes in red, versus downregulated genes in blue.

In the YB versus OB comparison, he says, "About half of the YB samples are red (higher expression), and half are blue (lower expression) compared to the OB samples. That gives an indication of the number of genes that will meet the criteria of differential expression based on selected p value difference and fold change difference."

Analysis

Researchers then used proprietary Procter & Gamble software to identify the functions of genes that met the differential expression criteria.

The Human Gene Ontology Consortium uses three classifications to characterize the properties of genes and gene products:

Although researchers noted differences between intrinsic aging and photoaging in some themes and specific genes, gene expression changes noted in chronological aging were similar, but enhanced, in photoaging.

The data show that targeting a specific enzyme to block a specific pathway involved in aging would likely prove insufficient.

Rather, Dr. Robinson says, "Approaches that might be more holistic and involve multiple pathways or could target multiple pathways might be more beneficial."

Since these approaches are ultimately used in cosmetic products, he says, "What you're looking for are cosmetically actionable ingredients. Often, you're looking for combinations of ingredients that might affect this process in subtle but different ways."