Repetitive Sequences Accumulate With Age, Says CSU Researchers
More than 60% of the human genome was believed to be ‘junk DNA’ for decades that have little or no function in human development. But this junk DNA might be important after all, according to recent research by Colorado State University.
Repetitive element transcripts, a kind of noncoding genetic material might be a useful biomarker of the aging process, says the new study published in Aging Cell on June 5.
As we age, the sequences that occur in multiple copies and the repetitive elements called transposons may become active over time, shows the study led by Tom LaRocca, a faculty member in the Columbine Health Systems Center for Healthy Aging at CSU and an assistant professor in the Department of Health and Exercise Science.
LaRocca the team of researchers focused on RNA transcripts, molecules that are transcribed from the DNA of repetitive elements, to test whether they increase in number with age.
LaRocca believes that ten to twenty years from now, we might be able to take certain measurements or samples from people in the doctor’s office and get to know what’s going on with them biologically so that we can best
treat them and increase their healthspan. If the repetitive elements are the biomarkers of aging, someday you get a measurement for the expression of these elements and understand the problem.For this study, the researchers used an existing dataset of RNA sequencing obtained from skin cells in healthy people aged between one and 94 and analyzed them. RNA sequencing can provide a map of the entire transcriptome in the cells under study just how the Human Genome Project of the 1990s was sought to map and sequence the approximately 20,500 genes in human DNA. Researchers found from the computational analysis that older human subjects had more transcripts from most major types of repetitive elements.
By performing their own lab analyses on skin cells from a biobank, the researchers verified their initial findings in the second wave of the study. They tagged the transcript of a transposon named Charlie5, using fluorescent microscopy to see how it varies with the age of cells. The more Charlie5 transcript was detectable, the brighter the tag appears under the microscope.
A marked accumulation of the Charlie5 transcript was revealed in skin cells from older adults compared to cells from younger individuals, as hypothesized. This showed that repetitive elements accumulate as we age. A crucial outcome of this study was that repetitive RNA transcripts might be linked to the health of a person’s cells or the biological age rather than chronological age in years.
Finding something that changes progressively with aging is not that interesting as many things increase or decrease with age. But, finding changes that reflect biological aging is something scientists really want to do.
Cavalier performed an analysis that compared skin cells that had not been exposed to sunlight to sun-exposed skin cells to study biological age. The cells will be more biologically older, the more damaging UV rays they are exposed to. Consistent with this, higher levels of repetitive element RNAs were found in the sun-exposed cells.
To further confirm the link between repetitive element transcripts and biological age, they studied an RNA-sequencing dataset from the roundworm Caenorhabditis elegans as well as the skin cells from patients with a premature aging syndrome called Hutchinson-Gilford progeria syndrome (HGPS).
The researchers suspect that the reason behind the increase in repetitive elements with age could be due to the disruption of chromatin — the complex of DNA and protein in cells that typically represses repetitive elements from being expressed, enabling the transcription of repetitive elements.
Evidence is growing those repetitive sequence transcripts, or the non-coding RNAs have a crucial role to play in regulating the human genome, and this study proves that they could be potentially targetable biomarkers of aging as they accumulate with age.
The researchers are now planning to understand how exercise impacts repetitive element levels by comparing the chromatin structures of people who don’t exercise with those who routinely exercise. There will also be studying to use drugs to inhibit repetitive element RNAs from being transcribed.
