60% of the human genome has been believed to be “junk DNA” for a long time, which means they serve little or no purpose in human development. But a recent research by Colorado State University just might debunk this long-believed theory.
Tom LaRocca, an assistant professor in the Department of Health and Exercise Science and a faculty member in the Columbine Health Systems Center for Healthy Aging at Colorado State University, led a team of researchers investigating the evidence that repetitive elements, namely transposons and sequences that occur in multiple copies in the human genome, become active as we age.
In their study, they found that these repetitive element transcripts may be an important biomarker of aging.
LaRocca, Alyssa Cavalier, a graduate student, and Devin Wahl, a postdoctoral researcher, tested RNA transcripts to see whether they increase in number as a person ages.
Standing by the importance of the biomarker angle in their study, LaRocca claims that 10 to 20 years from now, samples of people might be examined to see what is going on with them on a biological level. This would allow doctors to provide them with the best treatment plan to improve their healthspan. If the repetitive element RNAs are a biomarker of aging, then a person could get a measurement done to assess how their repetitive elements are being expressed.
To carry out their study, the team of researchers started by analyzing an existing RNA sequencing dataset gathered the skin cells of healthy subjects aged 1 to 94 years old. RNA sequencing can provide a map of the whole transcriptome in the cells, and from the computational analysis, the researchers discovered that repetitive elements increased in older subjects.
The researchers then verified their initial findings by analyzing skin cells from a biobank. By using fluorescent microscopy, the team tagged the transcript of Charlie5, a transposon, to see if and how it fluctuates with the cell age. The brighter the fluorescent tag appeared under the microscope, the more Charlie5 transcript present.
As predicted, the skin cells coming from older adults revealed more accumulation of Charlie5
Transcript compared against the skin cells from younger subjects, showing that repetitive element RNAs accumulate as a person ages.
Furthermore, an outcome of the study shows that repetitive RNA transcripts might be linked more with the biological age or health of a person’s cells rather than their chronological age. For example, the cells of a smoker under a lot of chronic stress might be 45 years old, but the health of their cells could be 60 or even older.
Cavalier also performed an analysis to compare skin cells that were exposed to the sun against skin cells not exposed to the sun to support or debunk the theory that a skin cell exposed to UV rays would be older biologically. As hypothesized, the exposed skin cells revealed higher levels of repetitive element RNAs.
The link between repetitive element transcripts and the biological age of cells was further confirmed by the team by studying skin cells from patients with HGPS or Hutchinson-Gilford Progeria Syndrome, a premature aging syndrome.
The team suspects that chromatin, which is the complex of DNA and protein in cells, might become disrupted in time, which allows for the transcription of repetitive elements.
For the longest time, this part of the genome was believed to be junk and serve no purpose, but this study shows that noncoding RNAs and repetitive elements actually play an important role in regulating the human genome, even serving as biomarkers of cellular aging.
LaRocca’s Healthspan Biology Lab plans to further these studies by comparing the chromatin structure in people who exercise regularly and those who do not, allowing us to understand the impacts of exercise on the biological level. They also plan on investigating the potential of using a drug to inhibit the transcription of repetitive element RNAs.
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