Fight Aging!

Neurogenesis is name given to the creation of new neurons in the central nervous system, and particularly the brain. Only within the last thirty years, quite recently in the grand scheme of things, have researchers proved that neurogenesis occurs at a low level in adults, that the brain is not a fixed set of long-lived and non-dividing cells, but is augmented with new arrivals on an ongoing basis. Once verified, this became a topic of considerable interest for the growing fields of regenerative medicine and stem cell research. Can the rate of neurogenesis be safely increased, and will this produce benefits for patients suffering neurodegenerative conditions, or postpone the onset of such conditions? Can investigation of neurogenesis be used to guide improvements in first generation stem cell therapies based on transplanted cells?

With more research into the biology of the brain, aided by the rapid improvement in the tools of biotechnology since the 1990s, there is an increased realization of the importance of adult neurogenesis. Few evolved processes exist without serving multiple ends, and this one is no exception in that regard. More than a mere repair and replacement mechanism, neurogenesis in adults is necessary to the correct functioning of the brain. Couple that to the discovery that rates of neurogenesis decline with age, and the processes of slow growth and change in the brain become ever more attractive as an area of medical research. It is worth noting that some of the recent work emerging from parabiosis studies, in which alterations are made to levels of some of the molecular signals in the circulatory system, have shown preliminary signs of being able to reduce the age-related decline in neurogenesis.

The article linked below is a good read, and goes some way to providing the high-level context and background to explain why research into neurogenesis is so important to those parts of the life science community focused on aging, age-related diseases of the brain, neurobiology, and regenerative medicine. Clearly there is a lot more to be done before an initial set of therapies emerge via the traditional drug development approach, and those therapies will likely be pretty marginal at the outset if history is any guide, but it is an interesting field to watch.

Brain Gain: Young Neurons in the Adult Human Brain are Likely Critical to its Function

At a lab meeting in the mid-1990s a neuroscientist told his team that he wanted to determine whether new neurons are produced in the brains of adult humans. At the time, adult neurogenesis was well established in rodents, and there had been hints that primate brains also spawned new neurons later in life. But reports of neurogenesis in the adult human brain were sparse and had not been replicated. Soon enough, a clear picture emerged: the human hippocampus, a brain area critical to learning and memory and often the first region damaged in Alzheimer's patients, showed evidence of adult neurogenesis. In November 1998, the group published its findings. "When it came out, it caught the fancy of the public as well as the scientific community. It had a big impact, because it really confirmed neurogenesis occurs in humans."

Fifteen years later, in 2013, the field got its second (and only other) documentation of new neurons being born in the adult human hippocampus - and this time learned that neurogenesis may continue for most of one's life. Neuroscientistists took advantage of nuclear bomb tests carried out during the Cold War. Atmospheric levels of carbon-14 have been declining at a known rate since such testing was banned in 1963, and researchers were able to date the birth of neurons in the brains of deceased patients by measuring the amount of carbon-14 in the cells' DNA.

In the late 1990s and early 2000s, researchers delved into the cell biology of neurogenesis, characterizing the populations of stem cells that give rise to the new neurons and the factors that dictate the differentiation of the cells. They also documented significant differences in the behavior of young and old neurons in the rodent brain. Most notably, young neurons are a lot more active than the cells of established hippocampal networks, which are largely inhibited. "For a period of about four or five weeks, while the newborn neurons are maturing, they're hyperexcitable. They'll fire at anything, because they're young, they're uninhibited, and they're integrating into the circuit."

To determine the functional role of the new, hyperactive neurons, researchers began inhibiting or promoting adult neurogenesis in rodents by various means, then testing the animals' performance in various cognitive tasks. What they found was fairly consistent: the young neurons seemed to play a role in processing new stimuli and in distinguishing them from prior experiences. This type of assessment is called pattern separation. While some researchers quibble over the term, which is borrowed from computational neuroscience, most who study hippocampal neurogenesis agree that this is a primary role of new neurons in the adult brain. The basic idea is that, because young neurons are hyperexcitable and are still establishing their connectivity, they are amenable to incorporating information about the environment. If a mouse is placed in a new cage when young neurons are still growing and making connections, they may link up with the networks that encode a memory of the environment.

While studying the function of hippocampal neurogenesis in adult humans is logistically much more difficult than studying young neurons in mice, there is reason to believe that much of the rodent work may also apply to people - namely, that adult neurogenesis plays some role in learning and memory. "Given that the dentate gyrus is so highly conserved and that the mechanisms of its function are so similar between the species - and given that neurogenesis is there in humans - I would predict that the general principle is the same." And if it's true that hippocampal neurogenesis does contribute to aspects of learning involved in the contextualization of new information - an ability that is often impaired among people with neurodegenerative diseases - it's natural to wonder whether promoting neurogenesis could affect the course of Alzheimer's disease or other human brain disorders. Epidemiological studies have shown that people who lead an active life - known from animal models to increase neurogenesis - are at a reduced risk of developing dementia, and several studies have found reduced hippocampal neurogenesis in mouse models of Alzheimer's. But researchers have yet to definitively prove whether neurogenesis, or lack thereof, plays a direct role in neurodegenerative disease progression.

Of course, the big question is whether researchers might one day be able to harness neurogenesis in a therapeutic capacity. Some scientists say yes. "I think the field is moving toward that. Neurogenesis is not something de novo that we don't have at all - that would be much harder. Here, we know it happens; we just need to enhance it."