In at least some portions of the brain, new neurons are created throughout life in a process called neurogenesis. This is vital to memory and learning, but declines with age. Faltering neurogenesis is arguably implicated in the development of some neurodegenerative conditions. As most of the evidence for neurogenesis in adult individuals has been established in mice, and in recent years there has been some debate over whether or not these same processes do in fact operate in humans. So far, the most recent evidence leans towards supporting the existence of human adult neurogenesis. Given this, the research community remains interested in developing means of increasing the pace of neurogenesis as a basis for therapies to enhance cognitive function in the old, but progress towards this goal remains slow.
Adult hippocampal neurogenesis has been proposed to be a key element in ensuring and maintaining functional hippocampal integrity in old age. Neurodegenerative diseases due to the age-dependent rapid and continuous loss of neurons (such as Parkinson's disease and Huntington's disease) have been suggested to reflect the contraposition of the neurogenic process such that under homoeostatic conditions a fine balance between neurodegeneration and neuroregeneration exists, and under pathological conditions, the balance is disturbed and a disease manifests. Even though little evidence has accumulated in support of this theory, if it proves correct, it in combination with findings regarding the high potential of stem-cell-based strategies for the treatment of age-related neurodegenerative disorders, make the hypothesis that adult neurogenesis holds a key to novel therapeutic approaches in the treatment of age-related neurodegenerative disorders rather attractive.
Decreased hippocampal neurogenesis is proposed as an important mechanism underlying age-related cognitive decline as well as neurodegenerative disorders such as Alzheimer's disease (AD) and various types of dementia. Evidence in this regard was recently published in two separate recent studies examining hippocampal neurogenesis in human tissue from people suffering mild cognitive impairment and AD. Both studies demonstrated a dramatic decrease in the number of neural progenitor cells and neuroblasts in hippocampal tissue from AD patients which was related to the stage of the disease. Interestingly, a decrease in the number of newborn neurons was observed in AD patients at the very early stage of the disease when the characteristic neurofibrillary tangles and senile plaques had not become prevalent. This suggests a potential for using neurogenesis levels as an early biomarker of the disease.
The mechanisms underlying the age-related decline in hippocampal neurogenesis remain poorly understood. It has been proposed that within the senescent brain the neurogenic niche may be deprived of the extrinsic signals regulating the neurogenic process or that the aged neural progenitor cells are less responsive to normal signalling within the niche, or both. The evidence accumulated thus far points to changes in the properties of the neurogenic niche with age, rather than changes in the phenotype of the stem cells or progenitor cells themselves. For instance, it has been reported that the numbers of neural stem cells and neural progenitor cells as well as the proportion of astrocytes to neurons in the hippocampus of young and aged rats remained the same; however, there was a decrease in the number of cells actively undergoing mitosis in the aged animals.