# spook  haploinsufficiency exacerbates aging-related motor impairments

**Authors:** Veronica C. Ciliberto, Maya Solis, Carolyne Chepkosgei, Paul Rafael Sabandal, Kyung-An Han

PMC · DOI: 10.17912/micropub.biology.001871 · 2025-10-15

## TL;DR

Reduced levels of a gene called spook in fruit flies worsen age-related motor problems, suggesting a key role for steroid signaling in aging.

## Contribution

The study identifies spook haploinsufficiency as a novel contributor to aging-related motor impairments through ecdysone signaling.

## Key findings

- spook heterozygous flies show accelerated aging-related motor decline in climbing assays.
- Reduced brain ecdysone levels are linked to impaired motor function without affecting basal activity.
- Ecdysone signaling is proposed as a conserved pathway contributing to aging-related motor impairments.

## Abstract

The global rise in aging populations heightens the risk of motor decline, reducing quality of life and increasing morbidities, yet aging-related motor impairments (AMI) remain poorly understood. Many steroid hormones synthesized by cytochrome P450 enzymes decline with aging but their role in AMI is unclear. Here we show that
spook
heterozygous flies with reduced brain ecdysone exhibit accelerated, aging-related declines in climbing performance in a stimulus-induced negative geotaxis assay, without affecting basal activity. These findings implicate ecdysone signaling as a critical regulator of aging-sensitive motor function and suggest a conserved steroid pathway contributing to AMI across species.

## Linked entities

- **Genes:** Cyp307a1 (cytochrome P450, family 307, subfamily a, polypeptide 1) [NCBI Gene 100127052]
- **Species:** Drosophila melanogaster (taxon 7227)

## Full-text entities

- **Diseases:** AMI (MESH:D008569), motor impairments (MESH:D000068079)
- **Chemicals:** steroid (MESH:D013256), ecdysone (MESH:D004440)

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC12572965/full.md

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Source: https://tomesphere.com/paper/PMC12572965