Time Lapsed Aging

As life expectancy increases more individuals retain good health lfor a longer time. However, also the risk of cancer, cardiovascular and neurodegenerative diseases increases with age. Today, neurodegenerative diseases take a significant toll as cause of death in old age. In Germany around one million individuals are affected by dementia. This number could triplicate by 2050. There is a fine line between healthy and pathological ageing and understanding the factors that control the ageing process is key to improve life quality for old individuals . At the DZNE in Bonn, Dr. Daniele Bano leads the “Aging and Neurodegeneration” research group. He and his team are researching the genetic causes and physiological mechanisms of aging processes to understand how neurodegenerative diseases develop.

In recent years, research projects have shown that aging weakens the connections between nerve cells. This loss of connectivity appears to be the cause of memory impairment in neurodegenerative diseases. Bano and his team are therefore working on identifying genes that could put a stop to this aging process in the brain. The test subject they selected is the Caenorhabditis elegans nematode, a tiny roundworm, less than a millimetre long, which has a life expectancy of just three weeks. It enables DZNE scientists to observe this accelerated aging process and obtain results far more quickly than with mice, which have a much longer life span. Nematodes are also more cost-effective, easier to breed and simpler to genetically manipulate. Some of the genes controlling aging in humans and worms are actually very similar. “We can perform basic genetic tests on roundworms to identify genes that are likely to play an important role in brain structure or neuronal physiology,” says Bano. “We then test those genes on higher life forms such as mice, to allow us to better transfer the results to humans.”

Roundworms live much longer than other worms, so the scientists are carrying out tests to pinpoint the genetic variations responsible for this. A variety of experiments using genetically modified test subjects allow the DZNE team to observe how the worms’ genetic make-up affects the aging process. The work involves targeting specific genes associated with the aging process and manipulating them so as to either accelerate their function, decelerate it, or turn it off entirely. Bano explains that his team is also examining what metabolic processes these genes are involved in and what role these processes play in human aging. “Today we know that metabolic changes in old age play a major role in causing nerve cells to malfunction and degenerate, which leads to neurodegenerative disease. However, we do not yet know exactly why that happens,” he says. Dr. Dan Ehninger’s research group is also exploring what impact aging has on neurodegenerative diseases. Since February 2010, Ehninger has led the “Molecular and Cellular Cognition” Young Investigators Group. He plans to build on the findings with the nematodes, using mice to understand the effects of aging and to explore how behaviour, learning and memory change as we get older. To gain this insight, Ehninger and his team will artificially delay the aging process in the mice.

Mice live longer when they are fed rapamycin, an immunosuppressant drug used in organ transplants. It affects the mTOR enzyme, which performs a variety of signalling and metabolic functions and is responsible for aging processes. While mTOR stimulates the production of proteins, it also inhibits catabolism within cells. Rapamycin intervenes in these metabolic functions, and in animal models of Alzheimer’s, the drug was found to significantly delay the onset of the disease. “We want to find out exactly why it prolongs life and slows the onset of disease. Obviously, we are also interested in how slowing the aging process affects brain aging and whether it can also postpone age-related learning difficulties,” says Ehninger.

Tests will examine how active Alzheimer’s genes combined with rapamycin affect both young and old mice. The researchers hope to find out how age affects the progress of the disease and whether different effects occurring in the brain could have an impact on the ability to learn. Ehninger explains that his group’s research activities will focus on the links between aging and neurodegeneration. “One of the questions we hope to answer is why neurodegenerative diseases usually appear at such a late stage. And of course we want our research to play a part in developing new therapeutic approaches through gaining a better understanding of neurodegenerative processes.”