A small-molecule screen identifies novel aging modulators by targeting 5-HT/DA signaling pathway.

Shi-Wei Ye, Shuang-Di Song, Xi-Juan Liu, Yun Luo, Shi-Qing Cai

Institute of Neuroscience and State key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China.Institute of Neuroscience and State key Laboratory of Neuroscience, CAS Center for Excellence in Brain Science and Intelligence Technology, Chinese Academy of Sciences, Shanghai, China. · pubmed

Paper

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 Ca

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Research summary

The paper identifies small molecules that modulate aging-related pathways in C. elegans, which is relevant to longevity research. However, the findings are based on a model organism and involve incremental advances in understanding the mechanisms of aging rather than groundbreaking discoveries. The impact is limited as the study primarily contributes to the screening of compounds without extensive validation or exploration of their mechanisms in more complex systems.

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