Endurance exercise protects aging Drosophila from high-salt diet (HSD)-induced climbing capacity decline and lifespan...

Area of Science:

• Aging research
• Genetics
• Physiology

Background:

• High-salt diets (HSD) contribute to age-related decline, including impaired mobility and reduced lifespan.
• Endurance exercise is known to mitigate various age-related diseases, but its protective effects against HSD-induced decline in aging individuals are not well understood.

Purpose of the Study:

• To investigate the impact of endurance exercise on HSD-induced impairments in climbing capacity and longevity in aging *Drosophila*.
• To elucidate the molecular mechanisms, specifically the roles of the *salt* gene and *dFOXO* pathway, in mediating these effects.

Main Methods:

• Aging *Drosophila* were subjected to endurance exercise and a high-salt diet from 1 to 5 weeks of age.
• Genetic manipulation (UAS/Gal4 system) was used to overexpress or knockdown the *salt* and *dFOXO* genes.
• Key physiological and molecular markers, including climbing ability, lifespan, gene expression, SOD activity, and malondialdehyde levels, were assessed.

Main Results:

• A high-salt diet, *salt* gene overexpression, and *dFOXO* knockdown significantly reduced climbing endurance, lifespan, and antioxidant capacity while increasing oxidative stress markers.
• Conversely, endurance exercise and *dFOXO* overexpression in HSD-fed aging flies significantly improved climbing ability, lifespan, and antioxidant function.
• Endurance exercise did not significantly alter *salt* gene expression but enhanced the *dFOXO*/SOD pathway.

Conclusions:

• A high-salt diet accelerates age-related decline in climbing capacity and mortality by upregulating *salt* expression and inhibiting the *dFOXO*/SOD pathway.
• Enhanced activity of the *dFOXO*/SOD pathway is crucial for mediating the resistance of endurance exercise to HSD-induced impairments in climbing capacity and longevity in aging *Drosophila*.