Ajou News

NEW Prof. Park Dae-chan’s team discovers a new way to control cellular aging

  • 2021-03-19
  • 6043


A team of researchers from Ajou and Seoul National universities has discovered a new way to control the pace of cellular aging. The key anti-aging solution found consists in the reconfiguration of telomeres, often understood as “timers” of cell division, which promises to unlock the secret of aging.

             

The findings of the latest research were published under the title, “Telomeres reforged with non-telomeric sequences in mouse embryonic stem cells” in the February 17 issue of Nature Communications, a prestigious publication on natural sciences, with Prof. Park Dae-chan (Departments of Biological Sciences and Molecular Science and Technology) from Ajou University and Prof. Lee Jun-ho from Seoul National University listed as corresponding authors. Kim Da-eun, currently studying molecular science and technology at Ajou’s graduate school, was also listed as a co-author.

             

The cells that make up the human body continue to divide and multiply to sustain the natural functions of life and growth. At some point in time, however, cells stop dividing, while some genetic information is lost as cells repeat division.

             

Telomeres are protective sheaths found at the tips of chromosomes that serve as a kind of shield against the loss of genetic information during cell division, as telomeres are lost instead of vital genetic information. As telomeres shorten to a certain length or below, cells stop dividing and begin aging. Cells that continue to divide more actively than others, such as reproductive cells, stem cells, and cancer cells, utilize an enzyme known as telomerase to maintain the telomeric lengths and continue to divide almost infinitely.

             

In other words, the continued healthy functioning of cells relies crucially on regulating the lengths of telomeres and the number of times cells divide. An accurate understanding of how telomeres can best be preserved may be essential to effective cancer treatment and anti-aging strategies with minimal or no risk of side effects.

             

Researchers have discovered a mechanism known as alternative lengthening of telomeres (ALT) in certain cancer cells, which maintains telomeric length without utilizing telomerase enzymes. In human cancer cells, however, researchers have so far found telomeres that utilize the ALT mechanism but whose sequences simply follow the general and repetitive pattern.


The researchers on Prof. Park’s team have discovered, for the first time in the world, a recombination of telomeres with unique sequences in a mammalian model. A small number of embryonic stem cells from a mouse with its telomerase inactivated went on to activate the ALT mechanism to recover the normal pace of cell division. The cells divided by this ALT mechanism displayed amplified unique sequences. 


Prof. Park’s team named the new pattern they discovered the mouse template for ALT (mTALT), arguing that it provided clues as to the possible existence of alternative telomeres in human cancer cells as well.


The researchers, moreover, employed a multi-omics analysis to trace how the ALT mechanism actually works, subjecting the mouse embryonic stem cells at diverse stages of growth—cells with normal telomeric lengths, cells in the aging stage, cells after ALT activation, etc.—to analyses of genomes, transcriptomes, single-cell transcriptomes, and proteomes. They were thus able to identify and demonstrate the molecular characteristics of ALT cells.


The researchers commented: “Our recent study reveals the possible existence of alternative telomeres in human cancer cells. We have demonstrated that the concept of telomeres extends beyond the repeated sequencing structures found at the tips of chromosomes and telomerase, but may also encompass diverse mechanisms that protect the tips of chromosomes.”


The research was made possible with support from the Ministry of Science and ICT and the National Research Foundation of Korea’s support programs for new and experienced researchers.




Mechanism of telomeric change and ALT activation due to cell division