In recent years a growing number of researchers have investigated the effects of putting old tissue into a young supporting environment. Typically this involves parabiosis: joining the circulatory systems of an old mouse and a young mouse. Given a knowledge what exactly is different between old and young environments, work also be carried out in cell cultures, however. Researchers have been using these methodologies to search for and evaluate potentially important signaling changes that occur with aging. Of particular interest are changes that impact stem cell populations, causing them to become less active, as the decline in stem cell activity with age is an important contribution to frailty and loss of function. In the research noted here, scientists are focused on cerebrospinal fluid and neural tissues rather than blood and the cardiovascular system, but find similar signs of an ability to spur greater stem cell activity in old tissue:
Researchers have discovered that the choroid plexus, a largely ignored structure in the brain that produces the cerebrospinal fluid, is an important regulator of adult neural stem cells. The study also shows that signals secreted by the choroid plexus dynamically change during aging which affects aged stem cell behavior. Stem cells are non-specialized cells found in different organs. They have the capacity to generate specialized cells in the body. In the adult brain, neural stem cells give rise to neurons throughout life. The stem cells reside in unique micro-environments, so-called niches which provide key signals that regulate stem cell self-renewal and differentiation. Stem cells in the adult brain contact the ventricles, cavities filled with cerebrospinal fluid (CSF) that bathes and protects the brain. The research team has now shown that the choroid plexus is a key component of the stem cell niche, whose properties change throughout life and affect stem cell behavior.
The researchers uncovered that the choroid plexus secretes a wide variety of important signaling factors in the CSF, which are important for stem cell regulation throughout life. During aging, the levels of stem cell division and formation of new neurons decrease. The research team showed that although stem cells are still present in the aged brain, and have the capacity to divide, they do so less. "One reason is that signals in the old choroid plexus are different. As a consequence stem cells receive different messages and are less capable to form new neurons during aging. In other words, compromising the fitness of stem cells in this brain region. But what is really amazing is that when you cultivate old stem cells with signals from young fluid, they can still be stimulated to divide - behaving like the young stem cells. We can imagine the choroid plexus as a watering can that provides signals to the stem cells. Our investigations also open a new route for understanding how different physiological states of the body influence stem cells in the brain during health and disease, and opens new ways for thinking about therapy."