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Aging Enhances Serotonergic Signaling via 5-HT7 Receptors Underlying Mechanical Alloknesis
Qiaofeng Zhao1, Alberto Leguina-Ruzzi2, Mitsutoshi Tominaga1
1Juntendo Itch Research Center (JIRC), Institute for Environmental and Gender-Specific Medicine, Juntendo University, Chiba, Japan.
Aging Cell
|July 13, 2026
Summary
Aging increases itch sensitivity, particularly to mechanical stimuli. Researchers found that blocking serotonin receptor 5-HT7 reduced this age-related itch, suggesting it as a therapeutic target for chronic pruritus in older individuals.
Area of Science:
- Neuroscience
- Gerontology
- Dermatology
Background:
- Chronic pruritus (itch) is prevalent in aging populations.
- Neural mechanisms of age-related itch hypersensitivity are not well understood.
- Serotonergic signaling's role in aging and itch is largely unexplored.
Purpose of the Study:
- Investigate the role of serotonergic signaling in age-related itch hypersensitivity.
- Determine if serotonin receptor 5-HT7 contributes to enhanced itch in aged individuals.
Main Methods:
- Utilized aged mouse models to study itch behaviors.
- Measured urinary serotonin levels and serotonin receptor 5-HT7 expression in sensory neurons and the spinal cord.
- Administered 5-HT7 receptor antagonists to assess effects on itch behaviors.
Main Results:
- Aged mice displayed heightened sensitivity to mechanical stimuli (mechanical alloknesis).
- Elevated urinary serotonin and increased 5-HT7 receptor expression were observed in aged mice.
- Blocking 5-HT7 receptors significantly reduced itch behaviors, especially mechanical alloknesis.
Conclusions:
- Serotonergic remodeling, specifically involving the 5-HT7 receptor, contributes to age-related itch hypersensitivity.
- Spinal 5-HT7 signaling represents a potential therapeutic target for managing chronic pruritus in the elderly.
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