Researchers uncovered the process behind premature aging. Two genes, namely spns1 and atp6v0ca, are involved in regulating normal cell function. A disturbance in spns1 can trigger degradation and premature aging while atp6v0ca can inhibit that degradation. The study was conducted by scientists from the Florida campus of The Scripps Research Institute (TSRI).
Their trials in zebrafish propose that these combined genetic disturbances can work against premature aging and can expand developmental lifespan.”We discovered that the double defects did really work against senescence throughout development and expanded the animal’s survival and life span,” mentioned TSRI Associate Professor Shuji Kishi. The results, published recently in the journal Autophagy, could also guide the discovery of future therapies for diseases that involve the body’s failure to degrade unwanted or harmful compounds.
Cellular senescence is when cells halt dividing and is a natural part of aging. Interestingly, senescence is not only found in later aging stages but is also observed during embryonic development in vertebrates.
In the recent study, the researchers observed the gene spns1. In vertebrates such as zebrafish and humans, the protein encoded by spns1 is significant in a cellular activity called autophagy, when the cell moves unwanted stuff to a cellular structure called the lysosome. Earlier research had described that defects in this gene can also lead to senescence in the embryonic stage and premature aging symptoms in adulthood.
But, Kishi and his colleagues discovered that a simultaneous interruption of another gene called atp6v0ca, whose sole defect still leads to senescence — causes inhibition of the process triggered by the defective spns1 gene. “Our results propose that these two defects, in fact, function at a balance point that is critically associated with the regulation of developmental senescence — and that balance permits normal cell function,” explained Kishi.
The scientists are currently considering ways to control the balance between these genes as an approach to treat lysosomal storage diseases like Pompe disease, where the excessive accumulation of glycogen leads to severe muscle weakness. They consider there may also be purpose in treating age-associated degenerative diseases related to late-stage autophagy disruption.
“The use of proper inhibitors, selective for key steps in the biosynthesis of cellular macromolecules in general, may repair normal dynamics in the autolysosomal section and rectify the pathological storage that is the ultimate reason of these types of disease,” said TSRI Research Associate Shanshan Lian, the co-first author of the study.
The results may also lead to the development of tools to facilitate the identification of new genes that are involved in the aging process without the need for carrying out lengthy adult lifespan analyses. This strategy could be applied to the high-throughput identification of pharmacological agents that regulate aging and lifespan by means of improved resistance to various stressors, including oxygen radicals.
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