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New Genetic Pathway Prevents Premature Aging: Study

by Iswarya on March 11, 2019 at 1:23 PM
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New Genetic Pathway Prevents Premature Aging: Study

Novel genetic pathway identified by a research team may help prevent premature aging, reports a new study. The findings of the study are published in the journal eLife.

The study investigated the activity of the geneáNORAD, a long noncoding ribonucleic acid, or RNA.áNORAD, which stands for Noncoding RNA Activated by DNA Damage, is present in many mammals and helps maintain the appropriate number of chromosomes as cells divide.

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Many RNAs in the cell serve as the instructions, or code, for building proteins, whereas noncoding RNAs do not encode proteins. "There are many questions in the scientific community regarding the importance of noncoding RNAs in mammalian physiology and development," saidáDr. Joshua T. Mendell, Professor of Molecular Biology at UTáSouthwestern and senior author of the study. "Our cells produce thousands of these RNAs, but only a few have been connected to important functions in animals."

In 2015, the researchers reportedátheir discovery of NORADáand demonstrated the importance of this noncoding RNA in maintaining the correct number of chromosomes in human cells. With their previous work limited to cells grown in the laboratory, the researchers next examined the role ofáNORADáin a living animal, to better understand the gene's function in mammalian physiology. To accomplish this, Dr. Florian Kopp,áa postdoctoral researcher in theáMendell labáand lead author of theáeLifeástudy, genetically engineered mice by deletingáNORADáfrom the genome.
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As was found in human cells, the loss ofáNORADácaused chromosomal defects in mice. But there were also some unexpected changes to mitochondria, the energy powerhouses of the cell.

"We were surprised to see that whenáNORADáwas removed, mitochondrial function became very abnormal. These mice also appeared to age very rapidly," said Dr. Mendell, a Howard Hughes Medical Institute (HHMI) Investigator, Cancer Prevention and Research Institute of Texas (CPRIT) Scholar in Cancer Research, and member of both the Hamon Center for Regenerative Science and Medicine and the Harold C. Simmons Comprehensive Cancer Center.

"We found thatáNORADáis critical for the proper regulation of two distinct processes - genome stability and mitochondrial function - both of which have been linked to aging. As a result of the defects in these processes, loss of this RNA results in a very dramatic premature aging phenotype," he added.

NORADáfunctions by binding to the protein Pumilio, Dr. Kopp explained.

"The normal function of Pumilio is to decrease the levels of hundreds of other proteins in the cell.áNORADáacts as an inhibitor of Pumilio," he explained. "WhenáNORADáis lost, Pumilio becomes overactive and reduces the levels of many proteins that participate in chromosome segregation during cell division and mitochondrial activity. Thus,áNORADáacts as a critical guardian of the genome and mitochondrial homeostasis by restraining Pumilio activity."

The researchers said there are some intriguing hints that regulation ofáNORADáor Pumilio plays a role in natural aging. For example, lower levels ofáNORADáand higher levels of Pumilio have been found in older people.

"We need to understand better how this pathway -áNORADáand its target Pumilio - are controlled in normal physiologic settings and in aging. If the disruption of this pathway is part of the aging process, then it will be important to understand the mechanisms through which this disruption occurs. Eventually, this research could lead to an ability to prevent or reverse the aging process," Dr. Mendell said.

"Another important line of investigation relates to whetheráNORADáis altered in any diseases - particularly premature aging syndromes known as progerias," he added.

Source: Newswise
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