Neurogenesis and Aging Workshop
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.
Workshop Agenda
Day 1: Monday, March 16, 2020
(All times are in U.S. Eastern Daylight Time)
8:15a Registration
8:45a Welcome & Introductions
Marie Bernard, MD, Deputy Director, National Institute on Aging
Eliezer Masliah, MD, Director-Division of Neuroscience, National Institute on Aging
Molly Wagster, PhD; Bradley Wise, PhD; and Amanda DiBattista, PhD; Division of Neuroscience, National Institute on Aging
9:00 Overview of adult mammalian neurogenesis in the hippocampus
Rusty Gage, PhD, The Salk Institute for Biological Studies, La Jolla, California
Session 1: Neurogenesis in the Adult Human Brain
9:45 Adult hippocampal neurogenesis and aging in health and disease
Maura Boldrini, MD, PhD, Columbia University, New York, New York
10:15 The role of hippocampal neurogenesis in aging- linked cognitive deficits and Alzheimer’s disease
Orly Lazarov, PhD, University of Illinois at Chicago, Chicago, Illinois
10:45 Break
11:00 Neurogenesis in the postnatal and adult human brain
Ionut Dumitru, PhD, Karolinska Institute, Stockholm, Sweden
11:30 Solving human neurogenesis in vivo toward better understanding and therapy of brain disorders
Mirjana Maletic-Savatic, MD, PhD, Baylor College of Medicine, Houston, Texas
12:00p Discussion—Bradley Wise, PhD, National Institute on Aging
12:30 Lunch
Session 2: Regulation of Neurogenesis in the Aging Brain
1:30 Regulation of neural stem cell aging with single cell approaches
Michael Bonaguidi, PhD, University of Southern California, Los Angeles, California
2:00 Enhanced plasticity of new neurons in the aging hippocampus
Alejandro Schinder, PhD, Fundación Instituto Leloir, Buenos Aires, Argentina
2:30 Embryonic origin and maintenance of adult neural stem cells
Hongjun Song, PhD, University of Pennsylvania, Philadelphia, Pennsylvania
3:00 Break
3:15 Blood-borne regulators of the hippocampal neurogenic niche
Joseph Castellano, PhD, Ichan School of Medicine at Mount Sinai, New York, New York
3:45 Transcriptional and epigenetic regulation of neural stem cell quiescence and activation
Ashley Webb, PhD, Brown University, Providence, Rhode Island
4:15 Adult neurogenesis and the neurobiology of individuality
Gerd Kempermann, MD, German Center for Neurodegenerative Diseases, Desden, Germany
4:45 Discussion - Amanda DiBattista, PhD, National Institute on Aging
5:15 Adjourn
Day 2 - Tuesday, March 17th, 2020
Session 3: Functional Significance of Adult Neurogenesis
9:00a The function of new neurons in adult and aging hippocampal neural circuits
Shaoyu Ge, PhD, SUNY Stony Brook, Stony Brook, New York
9:30 Blood: at the interface of aging and adult neurogenesis
Saul Villeda, PhD, University of California San Francisco, San Francisco, California
10:00 Pathological roles and mechanisms of aberrant neurogenesis in epilepsy
Jenny Hsieh, PhD, University of Texas at San Antonio, San Antonio, Texas
10:30 Break
10:45 Re-engineering and Rejuvenating aging memory circuits
Amar Sahay, PhD, Massachusetts General Hospital, Boston, Massachusetts
11:15 Harnessing Neurogenesis to Improve Pattern Separation in Aging
Rene Hen, PhD, Columbia University, New York, New York