# Dopamine Enhances Healthspan and Locomotor Performance via Antioxidant Defense in Silkworms, Bombyx mori

## TL;DR

This study shows that dopamine can improve the lifespan and movement of silkworms by boosting antioxidant defenses, suggesting new ways to delay aging.

## Contribution

The study reveals that peripheral dopamine administration can delay aging and improve locomotion in silkworms via antioxidant pathways.

## Key findings

- Moderate dopamine increases healthspan and locomotor activity in silkworms.
- Dopamine's benefits are linked to enhanced antioxidant capacity and are effective outside the brain.
- Excessive dopamine doses are toxic, and effects vary by sex and age.

## Abstract

As a key chemical messenger, the physiological roles of dopamine have been widely studied within the brain, but its precise effects on the aging process remain incompletely understood and lack a clear consensus. Here, we investigated the relationship between dopamine levels and both healthspan- and courtship-associated locomotor activity in the silkworm moth (Bombyx mori), an ideal model for aging research. By analyzing different silkworm strains with variations in endogenous dopamine levels in combination with pharmacological interventions, we showed that increasing dopamine enhanced the total antioxidant capacity, delayed aging, and improved locomotor activity. Importantly, we found that moderate administration in peripheral tissues (i.e., outside the brain) was enough to achieve these benefits and to reverse aging-related behavioral decline. Collectively, our work demonstrates that dopamine can modulate aging via pathways independent of the central nervous system, suggesting the potential for a novel therapeutic strategy to delay aging and providing a theoretical foundation for breeding more robust silkworms in sericulture via manipulation of dopaminergic pathways.

The impact of dopamine on aging is complex and context-dependent. This study systematically investigated the effects of dopamine levels on the lifespan and behavior of the silkworm moth by employing genetic mutants of the dopamine synthesis/metabolic pathway combined with pharmacological interventions. The results demonstrated a significant positive correlation between endogenous dopamine levels and adult lifespan. Reducing dopamine levels shortened lifespan, whereas a moderate peripheral administration significantly extended healthspan, improved locomotor activity, and restored motor vigor in aged moths, though an excessive dose was toxic. The lifespan-extending effect of dopamine was closely correlated with enhanced total antioxidant capacity, observed in both long-lived strains and dopamine-treated individuals. Dopamine’s effects also exhibited sexual dimorphism and age dependency. This research reveals that a moderate increase in systemic endogenous dopamine or peripheral dopamine administration exerts positive effects on lifespan and aging-related behaviors, an effect likely mediated by enhanced antioxidant defense. These findings not only advance our understanding of the role of dopamine in the aging process but also provide a novel theoretical framework for developing anti-aging therapies and breeding superior silkworm strains.