This 2016 German human skin study found:

“An age-related erosion of DNA methylation patterns that is characterized by a reduced dynamic range and increased heterogeneity of global methylation patterns. These changes in methylation variability were accompanied by a reduced connectivity of transcriptional networks.”

---

The study could have benefited from preregistration using an approach such as Registered Reports. As it was, the study gave the impression of a fishing expedition.

For example, the initial subjects were 24 women ages 18-27 and 24 women ages 61-78. The barbell shape of the subjects’ age distribution wouldn’t make sense if the researchers knew they were going to later use the epigenetic clock method.

The researchers did so, although the method’s instructive study noted:

“The standard deviation of age has a strong relationship with age correlation”

and provided further details in “The age correlation in a data set is determined by the standard deviation of age” section.

A second round of subjects were recruited, 60 women aged 20-79, “that also included intermediate ages.” No discrete numbers were provided, but from eyeballing Figure S1 in the supplementary material, the ages of the second group appeared to be evenly distributed.

The subject groups were lumped together to make findings such as:

“We observed a significant age-related hypermethylation of CpG island-associated probes. This effect was strongly enriched during two specific age windows, at 40–45 and 50–55 years.

Considering that our samples were exclusively derived from female volunteers, it seems reasonable to link the latter window to menopause, which is also known to distinctly accelerate skin aging.”

The study didn’t state that the second group of subjects were screened for menopause, or for use of hormone therapies or skin creams.

If the ages of the second group of subjects were evenly distributed, 6 of the 108 subjects would be ages 50-55. It wasn’t “reasonable to link” a small number of subjects to conditions for which they hadn’t been screened.

http://onlinelibrary.wiley.com/enhanced/doi/10.1111/acel.12470/ “Reduced DNA methylation patterning and transcriptional connectivity define human skin aging”