# The role of neural signaling pathways in costs of reproduction on aging

> **NIH NIH R01** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2022 · $370,971

## Abstract

Project Summary
Fitness trade-offs are thought to play a fundamental role in the genetic architecture of fitness traits, including
shaping genes relevant to human health. Reproductive costs, particularly those that influence lifespan and
late-age disease, have been explored at the phenotypic and population genetic levels in a wide range of
species, but little is known about their underlying biological mechanisms. In our work on the fruit fly,
Drosophila melanogaster, we have found that survival costs of reproduction are mediated by evolutionarily
conserved neuropeptides, that these peptides are dynamically controlled by neural circuits that influence
reproductive success, and that these circuits influence downstream metabolic networks. The goal of our
proposed research is to identify and characterize conserved neural signaling pathways that orchestrate the
control of costs of reproduction and influence their evolution. We propose a model whereby an individual’s
reproductive strategy, with its attendant effects on aging, is determined by neurological decisions in response
to a combination of that individual’s reproductive expectation and reproductive achievement. Importantly,
these decisions are independent of any physical or energetic effects associated with mating itself. We will test
this model using innovative approaches to identify the environmental cues and perceptive systems underlying
reproductive expectation and reward, as well as the signaling pathways that are influenced by these processes.
We will combine a reductionist approach, using single-gene mutations and advanced cell-biology techniques
for neuronal manipulations, with a systems and network biology approach to identify mechanisms underlying
reproduction and aging. When complete, this research will provide new insights into the cues that portend
reproductive success, the mechanisms through which those cues are interpreted, and their regulatory effects
on lifespan. These insights will aid our understanding of quintessential evolutionary and health issues –
including sexual conflict, reproductive investment, and aging.

## Key facts

- **NIH application ID:** 10380656
- **Project number:** 5R01AG063371-04
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** SCOTT PLETCHER
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $370,971
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10380656

## Citation

> US National Institutes of Health, RePORTER application 10380656, The role of neural signaling pathways in costs of reproduction on aging (5R01AG063371-04). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10380656. Licensed CC0.

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