05:56am Monday 23 October 2017

A new piece in the puzzle of understanding the aging process

Aggregated proteins in aged yeast cells

Aggregated proteins in aged yeast cells visualized using green fluorescent protein (GFP). The aggregated proteins can be seen as bright foci in the cells.

During aging, the functions in the body gradually decline. This is manifested in everything from wrinkles to decreased metabolism and deficient heart function. The impairment is caused by the gradual accumulation of damage within the cells of the body which eventually leads to loss of function and death.

One type of damage occurs on the cell’s proteins. Proteins are the workhorses in the cell and perform many vital functions. The older the cell becomes, the more damaged proteins accumulate. These damaged proteins tend to clump together into so-called protein aggregates. This can have devastating effects for the cell and contribute to its decline.

Protein aggregates have been linked to several age-related diseases that affect the nervous system, such as Alzheimer’s and Parkinson’s.

The cell’s defense against aging

In order to counteract this decline, the cell has developed an advanced network of defense mechanisms, including enzymes that prevent damage and enzymes that take care of the damaged components in the cell. Peroxiredoxins are enzymes that reduce damage in several ways.

Michael Molin– We and others have recently shown that reduced caloric intake slows down aging in yeast, flies and worms by stimulating peroxiredoxin activity. This is interesting because upon reducing the number of calories (reducing the amount of sugars and proteins), it has been shown that many different organisms (from yeast to monkeys) live a significantly longer life than expected. However, we still know relatively little about the mechanisms involved, says Mikael Molin, researcher at the Department of Chemistry and Molecular Biology, University of Gothenburg.

By showing that only a small increase in the amount of peroxiredoxin significantly prolongs the life-span of yeast, researchers have now further linked peroxiredoxin activity to the aging process.

An enzyme that affects aging

The results, published in the scientific journal Cell, show that peroxiredoxin (Prx) takes part in a mechanism that prevents the formation of protein aggregates when the levels of the harmful oxidant hydrogen peroxide increase in the cells.

Sarah Hanzén– Prx helps other enzymes finding their way to the damaged proteins so that these can be repaired and the accumulation of protein aggregates can be decreased. Without Prx, the amount of protein aggregates in the cell increases and the aging process accelerates. Conversely, increased Prx levels lead to fewer protein aggregates and to the aging process being slowed down, says Sarah Hanzén, PhD student at the University of Gothenburg and first author of the article.

If peroxiredoxin’s function in handling damaged proteins also is important in human cells, it is possible that, by stimulating these enzymes and thus the cell’s defense against the accumulation of damaged proteins, the onset of diseases such as Alzheimer’s and Parkinson’s can be prevented or at least delayed.

The article Lifespan control by redox-dependent recruitment of chaperones to misfolded proteins is published in the scientific journal Cell.

Link to the article: Lifespan Control by Redox-Dependent Recruitment of Chaperones to Misfolded Proteins

Contact:
Mikael Molin, docent at the Department of Chemistry and Molecular Biology, University of Gothenburg.
mikael.molin@cmb.gu.se, 031-786 2577, 0706-502971
Sarah Hanzén, PhD student at the Institute of Biomedicin, University of Gothenburg.
sarah.hanzen@gu.se, 0705-084243
Thomas Nyström, professor at the Institute of Biomedicin, University of Gothenburg.
thomas.nystrom@cmb.gu.se, 031-786 2582

Photos:
Photo 1: Aggregated proteins in aged yeast cells visualized using green fluorescent protein (GFP). The aggregated proteins can be seen as bright foci in the cells.
Photo 2 and 3: Mikael Molin and Sarah Hanzén

BY: Carina Eliasson – Translation: Katleen Burm
031-786 98 73


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