NOV 28, 2016 5:23 PM PST

Using Stem Cells to Understand Aging & Fight Neurodegeneration

WRITTEN BY: Carmen Leitch
An organism is dependent on the replenishment and maintenance of cellular proteins in order to survive. One family of proteins, chaperones, is responsible for protein quality control in a cell and aids in the folding of proteins into their proper three-dimensional structure. As organisms age, that ability is among those that degenerate, the result is a buildup of proteins of low quality – those that are damaged or misfolded and can cause cellular dysfunction and death. The accumulation of dysfunctional proteins, and a decline in the quality of proteins is seen as a hallmark of aging has been linked to neurodegenerative disorders like Huntington’s, Parkinson’s and Alzheimer’s diseases.
 
Long-lived germline-lacking C. elegans exhibit up-regulation of CCT expression in somatic tissues. Representative image of GFP expressed under control of the cct-8 promoter in adult wild-type and germline-lacking (glp-1(e2141)) worms. DAPI. / Credit: Alireza Noormohammadi and Amirabbas Khodakarami
 
Human pluripotent stem cells have the unique ability to continue to replicate, while remain undifferentiated – open to become any cell type and not specified to a certain type of cell. They are thus immortal, and while in that state, they are able to maintain critical balances in their protein content. That makes them a prime candidate for the investigation of how protein maintenance melds with aging.
 
Reporting in Nature Communications, researchers analyzed the mechanisms of global protein level maintenance in stem cells. "There is one chaperone system, the TRiC/CCT-complex that is responsible for folding about 10% of all the cellular proteins. By studying how pluripotent stem cells maintain the quality of their proteome, we found that this complex is regulated by the subunit CCT8," said the senior author of the study, David Vilchez.
 
That data enabled them to investigate the mechanism in a live organism – the roundworm. "Then, we discovered a way to increase the assembly and activity of the TRiC/CCT complex in somatic tissues by modulating this single subunit, CCT8. The increase resulted in prolonged lifespan and delay of age-related diseases of the model organism Caenorhabditis elegans," Vilchez explained.
 
"For this study we combined the results from human pluripotent stem cells and C. elegans, to have both in vitro and in vivo models, providing a more convincing approach. Our results show that expressing CCT8 as the key subunit of the complex is sufficient to boost the assembly of the whole system," said study first author Alireza Noormohammadi.
 
"It is very interesting that expressing this single subunit is enough to enhance protein quality and extend longevity, even in older animals," added Amirabbas Khodakarami, another study author.
 
"One of our next steps will be to test our findings in mice," said Vilchez. "We hope to make further progress in understanding aging diseases and to get closer to finding therapies against diseases like Huntington's or Alzheimer's. CCT8 could be a candidate to correct deficiencies in age-related diseases associated with protein dysfunctions."
 

 If you want to know more about misfolded proteins and their impact on human health, check out the short video above from the Penn Institute on Aging.
 
Sources: Phys.org via University of Cologne, Genes & Development, Nature Communications
 
About the Author
  • Experienced research scientist and technical expert with authorships on over 30 peer-reviewed publications, traveler to over 70 countries, published photographer and internationally-exhibited painter, volunteer trained in disaster-response, CPR and DV counseling.
You May Also Like
JUN 28, 2021
Cell & Molecular Biology
Bringing Light to Extracellular Vesicles
JUN 28, 2021
Bringing Light to Extracellular Vesicles
Though originally thought of as strictly a waste disposal system, extracellular vesicles (EVs) have been shown to have m ...
JUN 22, 2021
Cell & Molecular Biology
Taking a Close Look at Interactions Between Cellular Filaments
JUN 22, 2021
Taking a Close Look at Interactions Between Cellular Filaments
Cells exist in three dimensions, and they have a dynamic skeleton and filaments that help them maintain and stabilize th ...
JUL 11, 2021
Microbiology
COVID-19 Delta Variant Seems to Grow Faster & Be More Contagious
JUL 11, 2021
COVID-19 Delta Variant Seems to Grow Faster & Be More Contagious
In October 2020, what's now called the Delta variant of SARS-CoV-2 was first detected. It's now the most prevalent strai ...
JUL 15, 2021
Cell & Molecular Biology
Do Microbial Pathogens Have an Epigenetic Memory?
JUL 15, 2021
Do Microbial Pathogens Have an Epigenetic Memory?
Epigenetics are the parts of the genome that can affect the activity of genes but don't involve making changes to th ...
JUL 22, 2021
Cell & Molecular Biology
Cancer Cells in the Lab Aren't Like Cancer Cells in the Body
JUL 22, 2021
Cancer Cells in the Lab Aren't Like Cancer Cells in the Body
To study biology, researchers need models. Once those models might have been a bit limited to organisms like rats or mic ...
JUL 23, 2021
Genetics & Genomics
DNA Structure Affects Transcription & the Reverse May Also be True
JUL 23, 2021
DNA Structure Affects Transcription & the Reverse May Also be True
As imaging tools continue to get more sophisticated, researchers have been able to get a look at more biological process ...
Loading Comments...