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Updated: May 6, 2026
SA-β-Galactosidase-Based Screening Assay for the Identification of Senotherapeutic Drugs
Published on: June 28, 2019
A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway
Shi-Wei Ye1,2, Shuang-Di Song1,2, Xi-Juan Liu1
1Institute of Neuroscience and State key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.
Abstract:
The risk of many human diseases including cardiovascular diseases, cancer, neurodegenerative diseases, and musculoskeletal disorders rises significantly in the elderly. With the increase in the aging population, it is becoming increasingly important to understand the biology of healthy aging and develop interventions that slow down the aging process or prevent age-related diseases. In this study, by a high-throughput screen in Caenorhabditis elegans (C. elegans), we identified 11 small molecules that promote healthy aging. Among them, Carbamazepine (a voltage-gated channels inhibitor) and Calmagite (a calcium and magnesium indicator) enhanced serotonin (5-HT) and dopamine (DA) levels, extended lifespan, and preserved several important behaviors in aging C. elegans. These behaviors include slowing responses to food, pharyngeal pumping, locomotion, and male mating. Interestingly, we further found that administration of Carbamazepine or Calmagite alleviated hyperexcitability of aging male diagonal muscles and improved behavioral performance by ameliorating Ca2+ homeostasis. Mechanistically, administration of Carbamazepine or Calmagite induced nuclear translocation of the transcription factor DAF-16 and thus up-regulated its downstream genes numr-1/-2, which are known to promote resistance to metal-induced stresses and longevity. Taken together, our study offers a way for the discovery of drugs that promote healthy aging, and provides potential interventions for preventing behavioral deterioration in the elderly.
Insights
Researchers identified two small molecules, Carbamazepine and Calmagite, that promote healthy aging in worms by improving muscle function and extending lifespan. These findings offer potential interventions for age-related behavioral decline.
Area of Science:
- Gerontology and molecular biology research.
- Utilizes the model organism Caenorhabditis elegans for aging studies.
Background:
- Aging is associated with increased risk of diseases like cancer and neurodegeneration.
- Understanding healthy aging and developing interventions is crucial due to the growing elderly population.
Purpose of the Study:
- To identify small molecules that promote healthy aging using a high-throughput screen.
- To investigate the mechanisms by which these molecules affect aging and behavior.
Main Methods:
- High-throughput screening in Caenorhabditis elegans to identify aging-promoting compounds.
- Assessed effects of Carbamazepine and Calmagite on neurotransmitter levels, lifespan, and behaviors.
- Investigated molecular mechanisms including calcium homeostasis and transcription factor DAF-16 activity.
Main Results:
- Identified 11 small molecules promoting healthy aging, including Carbamazepine and Calmagite.
- Carbamazepine and Calmagite extended lifespan and preserved behaviors in aging C. elegans.
- These compounds improved muscle excitability and calcium homeostasis, activating DAF-16 nuclear translocation.
Conclusions:
- Carbamazepine and Calmagite enhance healthy aging by modulating neurotransmitter levels and improving physiological functions.
- The identified compounds represent potential therapeutic interventions for age-related decline.
- DAF-16 pathway activation is a key mechanism underlying the observed pro-longevity effects.
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