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cellregenerering i hälsa, sjukdom och åldrande

Reference number
F06-0031
Start and end dates
080301-131231
Amount granted
8 500 000 SEK
Administrative organization
Karolinska Institutet
Research area
Livsvetenskaperna

Summary

Much of the impetus in regenerative medicine is fuelled by the prospect of promoting cell replacement, or blocking unwanted cell production. Without knowing however, if a specific cell type is renewed in the healthy or pathological situation it remains uncertain whether it may be realistic and rational to modulate this process. Despite the importance of this information, remarkably little is known about the age of cells in many regions of the adult human body. This is largely due to difficulties in studying this process in humans. I have recently established methodology, by integrating biomedical approaches with recent developments in nuclear physics, which will allow one to establish the turnover of cells in human tissues. By measuring 14C derived from nuclear bomb tests in DNA, it is possible to retrospectively establish the birth date of cells. I propose to analyze clinical material to establish the dynamics of cells in the human body, with a focus on brain and adipose tissue. Knowledge on cell turnover will allow for the identification of diseases where therapies directed at modulating cell replacement would be beneficial. Given the novel and exploratory nature of the project it is quite likely that it will open additional avenues of research. This has already been the case, with the development of a new method to determine the age of human remains and aid in postmortem identification. I plan to develop this methodology and implement it as a world-wide forensic technique.

Popular science description

The human brain has traditionally been thought of as an organ incapable of regenerating itself, a belief supported by the poor ability of the central nervous system (brain and spinal cord) to repair itself after injury. It has however, in recent times been shown that new nerve cells are born in the adult rodent and primate brain, with one study even showing that new nerve cells are added to a region of the human brain involved in memory and learning. Such discoveries have generated much excitement and have lead to the death of the dogma, that the adult brain is incapable of making new nerve cells. Despite this excitement, remarkably little is actually known about cell turnover in the adult human brain. This is because, unfortunately, most techniques available to scientists for studying cell turnover in animals are not appropriate for use in humans. As a result much of our view on cell turnover in the adult human body is inferred from studies in animals, which in most cases are only a few months old at the time of analysis. This may not be an ideal model for man, who can live for a century, and potentially have a greater need to replace cells over a lifespan. I have recently established methodology which will allow one to establish the turnover of cells in human tissues. The genetic information of a cell is contained in two intertwined strands, called DNA. DNA is largely composed of carbon and thus determining the age of the carbon in the DNA will tell us how old the DNA is, and therefore the cell. During the latter period of the cold war there was extensive above ground nuclear bomb testing, leading to a massive increase in atmospheric levels of 14C. A Test Ban Treaty was signed in 1963, banning all above ground bomb testing and as a result atmospheric levels of 14C have been decreasing ever since. 14C exists in the atmosphere as CO2, and plants take up this CO2 as part of photosynthesis. Our consumption of plants, and of animals that live off plants, results in 14C levels in the human body paralleling those in the atmosphere. The level of 14C integrated into genomic DNA thus reflects the level in the atmosphere at any given time point and can be used to determine the age of cells. Applying this methodology to different organs can give us a map of the human body from a cell renewal perspective. Knowledge on cell turnover will allow for the identification of diseases where therapies directed at modulating cell replacement would be beneficial.