# Brain-wide screen for a neural pacemaker of aging

> **NIH NIH R01** · STANFORD UNIVERSITY · 2022 · $2,644,362

## Abstract

Summary
Aging is a gradual process that results in the loss of cellular function across the body,
leading to numerous chronic diseases that promote mortality. Elucidating the precise
mechanisms of aging is critical for reducing illness and extending healthy lifespan.
However, almost every tissue in the body is modified by aging, making it difficult to
pinpoint the principal controller of aging. The goal of this proposal is to determine
whether the brain modulates aging through coordinated activity patterns within discrete
neuronal networks. We will use one of the shortest-living vertebrates, the African
turquoise killifish, as a rapid, high-throughput model of aging to uncover genetically-
defined neurons that regulate cellular metabolism and lifespan. Employing large-scale
light-sheet imaging in killifish, we will visualize brain-wide calcium activity dynamics to
unbiasedly identify neurons that respond to longevity interventions. We will characterize
the genetic profiles of the identified neurons via a combination of immunohistochemical,
single cell, and phosphorylated ribosome capture approaches. To examine whether
these neurons play a causal role to control overall cellular function in the brain and other
tissues, we will optogenetically activate these neurons and measure molecular
signatures of youth and in vivo metabolic activity in the brain and peripheral tissues. We
will monitor and manipulate neural activity throughout the short lifespan of killifish using
fiber photometry to determine if this ‘neural pacemaker’ dictates the tempo of aging and
youthful behavior. These approaches will then be extended to longer-lived species –
zebrafish and mice. Knowledge resulting from these studies should be transformative to
understand the fundamental mechanisms that regulate and synchronize aging and
longevity. As age is the prime risk factor for many diseases, including neurodegenerative
diseases, this proposal should provide new, circuit-based approaches to treat these
diseases.
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## Key facts

- **NIH application ID:** 10437805
- **Project number:** 5R01AG063418-05
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** ANNE BRUNET
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $2,644,362
- **Award type:** 5
- **Project period:** 2018-09-30 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10437805

## Citation

> US National Institutes of Health, RePORTER application 10437805, Brain-wide screen for a neural pacemaker of aging (5R01AG063418-05). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10437805. Licensed CC0.

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