What causes ageing? What biological processes lie behind it? Academy Research Fellow Pekka Katajisto, who will become Director of the Academy of Finland’s Centre of Excellence in Stem Cell Metabolism at the University of Helsinki in early 2018, is exploring this theme. His fascination with the subject stems from the fact that, even now, surprisingly little is known about the actual causes of ageing.
“Ageing fades into the background and is treated as a biological phenomenon because it’s such a natural part of our view of the world. For a biologist, however, it’s natural to explore how tissue function is disrupted and how different cells affect the maintenance and continuity of functions. Where cancer researchers, for example, tend to focus on single-cell disturbances, the study of ageing must take account of how multiple cell interactions can deteriorate without dramatic changes at single-cell level.”
According to Katajisto, research on ageing has reached a breakthrough stage. It can now focus on the cells most relevant to ageing – the stem cells that control tissue regeneration. Enormous progress has recently been made in the understanding of tissue stem cell functions, and new tools are enabling researchers to understand the fundamental mechanisms of ageing.
Exploring the regenerative capacity of tissue
Among other things, Katajisto is studying the cells that protect and nourish stem cells and control their functions. He calls these niche cells.
“Niche cells not only protect and nourish stem cells, but also use a range of signals to control their functions, so that stem cells can maintain tissues in a balanced way. That enables the maintenance of good tissue function, despite possible changes. With ageing, the cellular activities of niche cells change, resulting in stem cells receiving the wrong messages or even lacking information on tissue status. As a result, the tissues either regenerate too slowly and their functional capacity deteriorates, or they over-regenerate, creating the risk of cancer,” Katajisto says.
Niche cells are different in every tissue. Katajisto explains that the niches themselves are difficult to describe because they are very different in different tissues. His group is studying communication between niche cells and stem cells, especially in the gut, since this organ adapts very quickly to changes in its environment and a great deal is known about its niche cells. The stem cells that control cell regeneration, and the cells that determine their functions, can be distinguished in the gut and combined or modified in the laboratory as desired. This enables the exploration of how communication between these two important cell types ensures the functional capacity of tissue.
“We’re studying whether the diminished regenerative capacity of ageing tissue is due to a communication breakdown between cells, or whether they’re even telling each other ‘alternative truths’ about the need for regeneration.”
How can deteriorating cell function be slowed down?
Katajisto’s group has discovered new ways in which niche cells control stem cell functions and identified how, during asymmetric cell division, selective inheritance between two daughter cells from certain ‘mother cell parts’, mitochondria, can control stem cell characteristics, or lead to cell death or differentiation.
“We’re hoping that our observations will enable us to safely increase tissue stem cell activity, or the number of such cells. We’re trying to develop means of repairing tissue damage, for example. This could also open up new ways of slowing the decline in tissue function and, say, maintaining muscle strength during ageing. Although we’re focusing on ageing-related problems in stem cell function, our research could offer new ways of promoting recovery from cancer treatments, for example. However, we’re not seeking the key to an eternal life.”
A boost from MIT
Katajisto’s research is so-called high-risk research, the springboard for which was a spell as a postdoctoral researcher at MIT in the United States, one of the world’s best universities. There, his supervisor was an enthusiastic supporter of Katajisto’s projects, since the subjects in question were relatively unrelated to his own research field. After returning to Finland, Katajisto established a research team that will continue based on the results obtained at MIT.
“The Academy of Finland’s research funding provided an important startup budget, with which we quickly produced results; based on these we have secured substantial funding from international organisations such as the EU. The Academy Research Fellow funding provides a young scientist with a clear time window during which to seek other funding and success.”
Text by Leena Vähäkylä
Photo by Matti Immonen