# Mechanistic study of declining hippocampal neurogenesis in the aging brain

> **NIH NIH R01** · STATE UNIVERSITY NEW YORK STONY BROOK · 2021 · $326,975

## Abstract

With an ever-aging population and an estimated prevalence of Alzheimer disease of 5.7 million people
in the United States alone, the impetus for more targeted treatments for age-related cognitive disorders is greater
now than ever. Neuroplasticity, the ability of neural networks to adapt and remodel given experience, dwindles
with age, providing possible mechanistic insights into this decline. An important layer of neuroplasticity, unique
to a couple of discrete areas of the adult mammalian brain, is the addition of newly-generated neurons into
existing circuits, a process known as neurogenesis. While the existence and importance of adult hippocampal
neurogenesis in young adults has been well-established, we know very little about hippocampal neurogenesis
in aging brains. Importantly, hippocampal neurogenesis continues into old age although there is a substantial
decline in the number of newborn neurons. For example, in 26-month-old rodents, ~1000 proliferating cells could
be detected per day, although only half that detected in 5-month-old adult rats. A recent study demonstrated that
thousands of new neurons could be detected in the aged adult human dentate gyrus, and further, that in patients
with Alzheimer disease, newborn neurons were fewer in number and exhibited delayed maturation. As a starting
point, we ask why neurogenesis declines in the aging brain. Based on our preliminary studies, we found that
biased circuit activity may regulate hippocampal neurogenesis in the aging brain. During screening of potential
molecules biasing circuit activity, we found that one sphingolipid signaling is active in interneurons and becomes
less active in the aging brain. We propose to genetically intervene this signaling to study its role in regulating
neurogenesis in the aging brain. Lastly, we determine how biased circuit activity regulates hippocampal
neurogenesis. Our results will not only provide mechanistic insights into the understanding of neurogenesis in
the aging brain it also provides a possible strategy to intervene aging circuit activity to regulate neurogenesis.

## Key facts

- **NIH application ID:** 10150745
- **Project number:** 5R01AG066912-02
- **Recipient organization:** STATE UNIVERSITY NEW YORK STONY BROOK
- **Principal Investigator:** Shaoyu Ge
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $326,975
- **Award type:** 5
- **Project period:** 2020-05-01 → 2025-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150745

## Citation

> US National Institutes of Health, RePORTER application 10150745, Mechanistic study of declining hippocampal neurogenesis in the aging brain (5R01AG066912-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10150745. Licensed CC0.

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