Workshop on Neurogenesis and Aging
Executive Summary
The National Institute on Aging (NIA) held a virtual workshop on March 16-17, 2020, on Neurogenesis and Aging. Neurogenesis may contribute to many critical processes in the brain, such as memory formation, learning, and pattern separation, and this process is compromised during aging. Although many studies have assessed the impact of neurogenesis on aging and vice versa, the underlying mechanisms remain poorly understood.
The goal of this workshop was to review current findings, discuss knowledge and research gaps, and identify priorities for future research in neurogenesis and aging. The workshop was organized into three sessions: (1) neurogenesis in the adult human brain, (2) regulation of neurogenesis in the aging brain, and (3) functional significance of adult neurogenesis. A concluding discussion was also held to express final thoughts and identify addressable gaps and opportunities in the field.
The study of neurogenesis during aging and age-related neurodegenerative diseases requires characterization of the many cell types and factors involved. Because increased neurogenesis can be harmful under some conditions (e.g., epilepsy), further investigation is necessary to understand (1) the precise level of neurogenesis that provides benefits during normal physiological conditions, aging, and in brain diseases (e.g., Alzheimer’s disease [AD]) and (2) whether the level of neurogenesis can be regulated through behavior or physiological intervention. Accurate characterization of neurogenesis in mouse models, non-human primates, and humans is essential to better understand the mechanisms underlying neurogenesis. Moreover, visualization of real-time neurogenesis processes is needed to move the field forward. Behavioral, genetic, and molecular interventions to regulate neurogenesis were discussed as strategies to improve cognitive outcomes during aging and in AD. Further assessment of how these interventions will translate to humans is required for wide-scale implementation.
Each session concluded with the identification of scientific gaps and opportunities to improve neurogenesis and aging research; two distinct topic areas emerged and are summarized below.
Mechanisms of Neurogenesis
- Impact of dysfunctional new neurons on the hippocampal circuit in aging and AD.
- Collective evaluation of the neurogenic niche (i.e., rather than separately assessing individual parts).
- Characterization of the neural stem cell niche in aging and AD (e.g., vascular, microglial, astrocytic, or peripheral factors).
- Identification of differences in neurogenesis between humans and model organisms.
- Exploration of both positive and potentially negative functional outcomes of newly integrated neurons in aging hippocampal circuits and in models of AD.
- Ideal balance of neurogenesis and mature neuron maintenance in aging and AD.
Experimental Tools and Resources
- New ‘omics’ or other markers for different stages of neurogenesis in the aging and AD brain, including those that distinguish between quiescent and active stem cells.
- Novel methods for tagging and monitoring newborn neurons, including molecular sensors, to study their incorporation into existing circuits that can be applied in aging and AD research.
- Standardization of tissue collection and processing procedures for studying neurogenesis.
- Live imaging approaches (i.e., magnetic resonance imaging, magnetic resonance spectroscopy, positron emission tomography, multimodal) to capture neurogenesis in humans and/or animal models to be applied for the study of both aging and AD.
- Multi-laboratory collaborations.