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Are All Protein Aggregates in Aging Exclusively Harmful?

Over the course of aging, proteins of many different varieties form aggregates in and around cells - this is one of the characteristic differences between old tissue and young tissue, which leads to the SENS rejuvenation research point of view that we should work to remove all of these aggregates. Any difference between old and young tissue should be reverted. Some aggregates are metabolic waste, some are misfolded or damaged protein machinery, and few are well understood at the detail level of their relationship with aging and disease. Where that understanding exists it is pretty clear that aggregates are causing pathology, but the present state of knowledge still leaves the door open to suggestions that at least some of these aggregates are helpful. Their presence perhaps compensates for other forms of age-related damage, or is the result of other compensatory behavior while the aggregates themselves are not particularly harmful. Still they are not present in young tissue, and this should perhaps remain the guide for development of rejuvenation therapies:

We age because the cells in our bodies begin to malfunction over the years. This is the general view that scientists hold of the ageing process. For example, in older people the cells' internal quality control breaks down. This control function usually eliminates proteins that have become unstable and lost their normal three-dimensional structure. These deformed proteins accumulate in the cells in a number of diseases, such as Parkinson's and Alzheimer's. For some researchers, however, the view of the ageing process as a consequence of flawed cell function and disease is too narrow. It ignores the fact that the mentioned so-called prion-like protein accumulations could have a positive effect, too, and therefore should not be referred to as cellular malfunction.

The researchers drew this conclusion based on research on yeast cells. They recently found in these cells a new type of protein aggregate, which appears as the cells get older. As the scientists were able to show, these protein aggregates do not arise as the result of a cell's malfunctioning internal quality control. On the contrary: in yeast cells with such aggregates, quality control functions even better. "It certainly seems that these aggregates help yeast cells to cope with the physiological changes caused by ageing. We are very exited to learn what type of information is stored in these structures." The scientists assume that these age-associated aggregates are formed by several different proteins. The researchers have already identified one prion-like protein that is part of the accumulations. What other proteins are involved and why the aggregates remain in the parent cells during cell division are subjects of further research.

"We're still a fairly small group of scientists who say: aggregate proteins are not pathological - they are neither an accident nor a defect." Rather, these proteins aggregate because it is their normal function. Diseases such as Parkinson's and Alzheimer's only arise when the system becomes imbalanced and too many prion-like proteins accumulate in the wrong place in the cells. "There are two aspects to ageing. Yes, you die at the end of the process, and this is negative. But you die wise. And Alzheimer's is perhaps a bad end to a good thing."

Link: https://www.ethz.ch/en/news-and-events/eth-news/news/2016/01/in-defence-of-pathogenic-proteins.html

Comments

"There are two aspects to ageing. Yes, you die at the end of the process, and this is negative. But you die wise. And Alzheimer's is perhaps a bad end to a good thing."

Huh? We die wise? Aging is a good thing?

Posted by: Antonio at January 12th, 2016 6:54 AM

I think the researcher is trying to draw an analogy between the beneficial aspects of being older, gaining knowledge and experience, and his view of the type of protein aggregation he is investigating. Pulling in Alzheimer's, which is the primary example of protein aggregation as a bad thing, is to emphasize his argument that pathological protein aggregation is beneficial protein aggregation run down and run wild.

I don't think I buy the broader argument, but I wouldn't be completely surprised to see one or more forms of beneficial protein aggregation, at least in their initial stages.

Posted by: Reason at January 12th, 2016 7:16 AM

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