# Determining the neural mechanisms of mechanosensory food perception in DR-mediated longevity

> **NIH NIH F31** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2024 · $42,575

## Abstract

Project Summary:
The field of geroscience has identified multiple genetic, pharmaceutical, and lifestyle interventions
that promote longevity and delay the onset of age-related disease. One of the most studied of these
interventions is Dietary Restriction (DR), or a reduction in nutrient intake that does not cause
malnutrition. DR can extend lifespan and healthspan across taxa, and many of the genetic
mechanisms of DR were originally discovered in the nematode Caenorhabditis elegans.
Unfortunately, dietary restriction is not a realistic solution to prevent age-related disease on a
population level because following a DR protocol is very difficult for most people and because the
benefits of DR can be blunted by environmental factors. For example, exposing fasted animals to
food smells decreases the efficacy of DR in multiple model organisms. In C. elegans, food smells are
perceived by sensory neurons that initiate circuits leading to neurotransmitter release from
serotonergic and dopaminergic neurons. Signaling from these bioamine neurotransmitters ultimately
conveys food availability information to the intestine through cell nonautonomous signaling. In the
intestine, this signal suppresses the expression of fmo-2, a gene required for DR-mediated longevity.
In the preliminary data collected for this proposal, we found that a second mode of food perception,
mechanosensation of food, also suppresses DR-mediated fmo-2 induction and longevity in C.
elegans. Much like food smell, mechanosensory suppression of DR requires the production of
bioamine neurotransmitters to drive cell nonautonomous regulation of peripheral longevity genes.
This project will identify key neurons and signaling components of the cell nonautonomous signaling
pathway through which mechanosensory food perception regulates aging. To map this circuit, I will
first identify the dopaminergic and tyraminergic neurons activated by mechanosensory food
perception and determine whether mechanosensation increases or suppresses release of these
neurotransmitters (Aim 1). Next, I will investigate elements of this pathway downstream of
bioaminergic neurons by 1) determining the bioamine receptor-expressing interneurons directly
downstream of the bioaminergic signal, and 2) identifying neuropeptides and neuropeptide receptors
through which information about the food environment is conveyed to the intestine (Aim 2). Together,
these aims will enhance our understanding of how different modes of food perception regulate aging
through conserved signaling elements. Ultimately, we can use this information to create
pharmaceuticals that mimic the benefits of dietary restriction regardless of environmental food cues.

## Key facts

- **NIH application ID:** 10904672
- **Project number:** 5F31AG084146-02
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Elizabeth Sarah Kitto
- **Activity code:** F31 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $42,575
- **Award type:** 5
- **Project period:** 2023-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10904672

## Citation

> US National Institutes of Health, RePORTER application 10904672, Determining the neural mechanisms of mechanosensory food perception in DR-mediated longevity (5F31AG084146-02). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10904672. Licensed CC0.

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