Israeli researchers release findings on how body deteriorates with age
While the deterioration had been previously demonstrated in worms, Technion recreated the conditions in human cells and presented its findings in the context of heat stress.
By JERUSALEM POST STAFFUpdated: DECEMBER 14, 2020 14:36Doctoral student Amal Younis(photo credit: RAMI SHLUSH / TECHNION)
Researchers at Technion - Israel Institute of Technology have released findings that could explain why the body deteriorates with age.According to the study, a body's protein quality control system deteriorates with age, and considering this system protects cells from accumulating damaged proteins, when the system is damaged or not working properly it causes clusters of these proteins to form and produces a "toxic effect, particularly.. in the brain."The study explains that proteins take part in all biological processes, and physically they depend on a specific three-dimensional structure to interact normally will other cell components.When proteins "misfold," as they tend to do with age, the proteins can not only function properly but it also causes them to become "sticky" and accumulate in clusters. These aggregations can lead to the development of neurodegenerative diseases, including Alzheimer’s, Parkinson’s, ALS and Huntington’s."Protein damage occurs frequently, and during the course of evolution a cellular control mechanism has evolved that tests the quality of proteins from the moment they are synthesized (“born”) on the ribosome until they die," Technion explained in a statement. "This mechanism, called proteostasis, identifies damaged proteins and deals with them in one of three ways: it refolds them; sequesters and inactivates them so they will not affect cellular activity; or sends them to the proteasome, the cellular trash can.""This mechanism ensures that damaged proteins, which occur in healthy cells as well, are treated and do not accumulate to form toxic aggregates, such as those that lead to neurodegenerative disease," it added. "However, the aging process involves the deterioration of the proteostasis mechanism."While the deterioration had been previously demonstrated in worms, Technion recreated the conditions in human cells and presented its findings in the context of heat stress.The findings showed that in aged cells response to stimuli, in this case heat, was found to have "deteriorated significantly.""Although senescent cells showed stress sensing, unlike young cells they were unable to trigger the unfolded protein response (UPR) and the heat shock response (HSR), related transcriptional responses necessary to fully overcome the stress," the university stated. "Two important stress transcription factors, which are responsible for mounting this response, were found to mis-localize and not fully enter the cells’ nucleus.""The researchers also found the function of the proteasome – the cellular trash can – was impaired following heat stress in aging cells, and did not recover even after given time to recover from the shock," it concluded.
The study - conducted by Technion Assistant Professor Reut Shalgi, research fellows Niv Sabath and Flonia Levy-Adam, and PhD student Amal Younis - was peer-reviewed and published in the PNAS medical journal.
