Improving Protein Stability By Learning From Stem Cells

Certain types of stem cells can sustain a culture of cells indefinitely, and one of the ways they do this is by increasing protein maintenance. Finding ways to copy this activity could help combat age-related decline

Pluripotent stem cells, including the embryonic variety, need to remain in good health to do their job. One of the ways they sustain division is through expression of telomerase, which prevents their telomeres from shortening with each division. Telomeres are only one issue however, and it's also important that these cells maintain a healthy protein balance (called proteostasis), ensuring correct folding and removal of faulty proteins. A new study has discovered a particular protein called CCT8  regulates an important chaperone system in these pluripotent cells, and could confer longevity benefits when enhanced in other cells too.

"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. 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"

 Overexpression of CCT8 shown here through GFP fluorescence. Credit: Alireza Noormohammadi and Amirabbas Khodakarami

An important protein chaperone complex called TRiC/CCT is upregulated in pluripotent cells, and assists in keeping tabs on protein folding. Without various chaperone systems proteins would fold incorrectly, and as expected stem cells appear to express at least some of these chaperone systems at a higher level than ordinary cells do. Researchers studying these cells found that a critical subunit protein called CCT8 was a limiting factor in expression of TRiC/CCT  - meaning when they increased CCT8 levels it was able to boost levels of the entire complex. This boost then appeared to improve protein 'health' in the model organism C. elegans; prolonging lifespan and delaying the onset of age-related disease. 

"One of our next steps will be to test our findings in mice. 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"

A loss of proteostasis is one of the major constants in the aging process, across the entire tree of life. Finding ways to boost protein maintenance is therefore a very important target. Copying from cells that already do this is a good place to start.