Discovery of telomere-encoded proteins spurs work on blood test for biological age

By Nick Paul Taylor, The Science Advisory Board contributing writer

February 21, 2023 -- The discovery that telomeres, previously considered noncoding DNA, are involved in the production of two proteins is spurring interest in the development of a blood test for biological age.

Telomeres are sequences of DNA at the tips of chromosomes. The unique, repeating DNA sequences that define telomeres stop chromosomes from fraying or sticking to each other. Every time a cell divides, the telomere becomes slightly shorter. The progressive shortening is associated with cancer pathogenesis and cell deterioration and death, making telomeres a key focus of anti-aging research.

Because telomeres consist of the base sequence TTAGGG repeated thousands of times, researchers have grouped them with non-coding parts of the human genome. A paper published in the Proceedings of the National Academy of Science challenges that established position.

Taghreed Al-Turki, PhD, and Jack Griffith, PhD, researchers at the University of North Carolina School of Medicine, began investigating whether telomeres encode proteins after seeing a paper released in 2011. The earlier study described the discovery of an RNA molecule containing a six-base repeat that produced toxic proteins implicated in a genetic form of amyotrophic lateral sclerosis.

Noting the similarity between the RNA described in the 2011 paper and the RNA generated from human telomeres, Al-Turki and Griffith ran experiments to show if the DNA region can produce proteins. The work showed telomeric DNA can tell the cell to make two signaling proteins, VR (valine-arginine) and GL (glycine-leucine).

The collaborators chemically synthesized VR and GL and analyzed their properties using microscopes, both electron and confocal, and biological methods. The analyses showed that the VR protein is found at elevated levels in some human cancer cells and in the cells of patients with diseases associated with defective telomeres.

Based on the findings, the researchers think the two signaling proteins are involved in cancer, aging and cell-to-cell communication, and that levels of VR and GL will rise steadily as the body ages and telomeres shorten. Griffith, the Kenan Distinguished Professor of Microbiology and Immunology and member of the UNC Lineberger Comprehensive Cancer Center, sees a chance to determine biological age.

"Based on our research, we think simple blood tests for these proteins could provide a valuable screen for certain cancers and other human diseases. These tests also could provide a measure of 'telomere health,' because we know telomeres shorten with age," Griffith said in a statement. "Many questions remain to be answered, but our biggest priority now is developing a simple blood test for these proteins. This could inform us of our biological age and also provide warnings of issues, such as cancer or inflammation."

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