“The whole project aims at finding new ways to address the problems of aging and, in the long term, to slow down or treat the onset of age-related diseases such as neurological diseases and dementia,” explains Martin Ott, professor at Stockholm University.

In times when the general life expectancy increases, society is facing a growing challenge to provide an aging population with welfare and healthcare. It is therefore an urgent task to unravel the basic principles of biological aging, whose details are found at the cellular level.

Organelles are the cell’s equivalent to the body’s organs, each fulfilling a specific function. Previous research has shown that in aging cells, the various organelles stop functioning one after the other, but it is unclear what causes this observation. Because the organelles are coordinated to counteract damage to proteins that occur in cells, their interdependencies are of great importance for aging and health.

Communication problems

One of the cell’s organelles is the mitochondrium and it acts as the cell’s power plant. The new study lead by Martin Ott shows that it is production of mitochondrial proteins that controls the well-being of the whole cell via previously unknown communication links. When mitochondria are exposed to stress, a protection program is activated to keep all the functions of the cell in check, a mechanism that also operates when cells age. Importantly, the study shows that in aging cells, this communication between the organelles collapses, which causes vital cellular functions to deteriorate or fail.

“It has been a very rewarding and inspiring collaboration where each research group has contributed with key expertise. What we now want to investigate is when, how and why communication between cellular organelles ceases to function during aging.” says Claes Andréasson, a lecturer at Stockholm University and a senior author of the study.

The discovery is based on studies of yeast cells. Although yeast may seem to have few similarities with humans, the mechanisms that control aging at the cellular age are essentially the same. Therefore, it is highly likely that the aging mechanisms identified at the cellular level in this study are also active in human cells.

About the article:

“Mitochondrial Translation Efficiency Controls Cytoplasmic Protein Homeostasis” was published in Cell Metabolism (2018), https://doi.org/10.1016/j.cmet.2018.04.011

The study is part of the collaborative project “Interconnected quality (IQ) control – role in organizational structure function, aging and longevity assurance”, which in 2017 was awarded a project grant of SEK 44.7 million by the Knut and Alice Wallenberg Foundation.

Five research groups at the University of Stockholm and Gothenburg are involved in the project led by Professor Thomas Nyström at the University of Gothenburg. The researchers in Gothenburg focus on investigating the shape of aging yeast cells, which is examined by high-resolution electron microscopy, and on the identification of genes that modulate aging. The colleagues in Stockholm study the proteins that these genes code for in order to figure out exactly what these proteins do in the cell.