Researchers Find Genetic Sequence Involved in Age-Related Changes in Gene Expression

A new study has identified a genetic sequence that may be involved in regulating age-associated changes in gene expression.

As we age, certain segments of our DNA are expressed less, others more frequently, leading to changes in protein production and cellular function (which can present with skin changes and other organ dysfunction). These age-related changes have, to this point, been poorly understood, although there has been some speculation that they are caused by changes in expression of long non-coding RNA (lncRNA) molecules as we grow older.

LncRNA molecules are genetic segments that, after being created from a DNA template, do not supply the blueprint for making proteins. Rather, they are used to regulate activity at other genes based on a number of factors (cell type, environmental stressors, etc.). More than 14,000 of these lncRNA molecules have been identified, but it is thought that there are tens of thousands of others still to be discovered.

Researchers from BUSM compared the expression patterns of lncRNA molecules in skin cells from young donors (under 30 years of age) to those from older donors (over age 60).

They found that, of the thousands of lncRNA molecules studied, only one (the FLJ46906 lncRNA) was consistently expressed at higher levels in older adults. Once this sequence was identified, the group showed that the FLJ46906 molecule binds to (and increases the activity of) transcription factors involved in inflammation, one of the processes that is known to be altered with aging.

Corresponding author Thomas M. Rünger, MD, PhD, professor of dermatology, pathology, and laboratory medicine at BUSM, feels that this is a major step forward. “This establishes that lncRNAs do play an important role in the aging process and provides a molecular understanding about how the expression of aging-associated genes is altered with aging.” However, he recognizes that there is still work to do. “This raises the question what causes the change in the expression of FLJ46906 during aging. At this time, this question remains unanswered.”

These findings appear online in the journal AGING.