Wallenberg Academy Fellows
Aging better with healthy stem cells
Pekka Katajisto’s vision is sprightly 90-year-olds. He is researching into how stem cells stay young and alert. It has been shown they divide asymmetrically in order to discard older cell parts. Greater knowledge of these mechanisms may keep us healthier in later life.
Human aging is a major field of research in medical science, as Pekka Katajisto points out from his new office at Novum, a research park at Karolinska Institutet in Huddinge, south of Stockholm.
“These days the main cause of death is age-related disease. Most of the diseases that are heavily investigated, such as cancer, are linked to the aging process.”
Our cells and tissues are constantly being renewed by dividing cells, some more quickly than others. This renewal tapers off over time, causing our organs to age. Pekka Katajisto is researching into stem cells and aging. He stresses that aging is due to many factors acting in concert, and his research does not aim to make us immortal.
“But during my career I really hope we will discover things that will help us to age better. One example is whether we can delay sarcopenia, which is the loss of muscle mass that comes with age. Another is to combat various forms of dementia.”
Stem cells are non-specialized cells that divide to form two daughter cells: one new stem cell and a specialized cell. A distinction is drawn between embryonic stem cells, which are found in the fetus, and adult stem cells in adult individuals.
Pekka Katajisto is studying adult stem cells, whose task is to repair and replace damaged cells in our organs and tissue. He argues that if stem cells can be kept healthy, they should also be able to continue producing new cells for longer.
Pekka Katajisto’s studies have revealed that mitochondria – the powerhouses of the cell – segregate asymmetrically when stem cells divide. His findings were published in Science in summer 2015.
“We have shown that one of the daughter cells, i.e. the new stem cell, receives the younger cell parts; the other, specialized, cell receives everything that is doubtful or damaged. This division maintains the vitality and function of stem cells.”
Stem cells talk to the cells around them, which plays a key part in cell division. Pekka wants also to understand how this interaction changes as we age, and whether it can be manipulated.
“Aging may be nothing but wrongly informed stem cells. Neighboring cells give the wrong guidance, so stem cells no longer form enough new tissue.”
It began with polyps
Pekka Katajisto studied biology at Helsinki University, where he also gained his PhD. His research at that time was about how polyps form in various hereditary diseases of the stomach and intestines.
“Even back then I discovered the importance of the communication between two cell types – smooth muscle and epithelial cells, the cell layer covering the inside of the intestines.”
As a postdoctoral student at Whitehead Institute for Biomedical Research at MIT in Boston, U.S., he continued to study these two issues. Pekka was a member of the team working under Professor David Sabatini, who gave him great freedom and time for reflection.
“He urged me to think of something completely new. I have always been interested in the aging process, but did not know how to approach the problem. Having pondered the matter for six months, I came up with the idea of asymmetric cell division. It has been studied a lot in model organisms, but surprisingly little in stem cells of mammals.”
Guided by the micro-environment
Since 2013 Pekka has headed a research team at the Institute of Biotechnology at Helsinki University. In summer 2015 he began commuting to Stockholm to set up a new research team at Novum with the help of funding from the Knut and Alice Wallenberg Foundation.
“I am impressed by the research environment here, and delighted with the opportunities presented by generous funding and high-class equipment. Naturally, the labs are collaborating to start with, but more of the research will gradually shift to Novum.”
The team is collaborating with other researchers at Karolinska Institutet, and also with scientists at ETH in Switzerland and Harvard University.
“We are now studying how the asymmetry of cell divisions is regulated by their surroundings. We have found that the micro-environment around the cell guides its behavior. At the same time we are trying to understand how cells can distinguish an old, worn-out mitochondrion from a young one. We have no idea how they do it.”
“The Fellows Program offers a great opportunity to build up a network and establish valuable relationships with the other researchers. We already get together outside the official meetings, and have also initiated collaborations, which is really great.”
Advanced lab offers new potential
Just down the corridor is the lab where the researchers are studying living cells. It is dark inside. The tiny amounts of fluorescent light used to identify old mitochondria would be lost in a well-lit room.
“The equipment available to us here is fantastic. We can do virtually everything we want now.”
When the research team has learnt how stem cells recognize organelle age, they will make the cells blind to this, and see whether they can get tissues to age more quickly. Then they will create a mouse incapable of identifying the age of mitochondria, for example, and study whether the mouse, too, ages quickly.
“What we have found out so far is great, but now we want to understand the part these mechanisms play in the aging process,” Pekka Katajisto concludes.
Text Susanne Rosén
Translation Maxwell Arding
Photo Magnus Bergström