Gerotherapeutic compound picolinic acid supports locomotor function and bone health in aged zebrafish

TL;DR

Picolinic acid improves movement and bone health in older zebrafish, possibly by reducing cellular aging.

Contribution

This study demonstrates that picolinic acid supports locomotor and musculoskeletal health in aged zebrafish.

Findings

Picolinic acid-treated groups showed higher swimming speeds compared to the control group.

Groups receiving oral gavage showed more advanced fin regeneration and stronger β-galactosidase staining.

Picolinic acid may influence regenerative outcomes through mechanisms related to cellular aging.

Abstract

This study aimed to evaluate the impact of picolinic acid (PIC), a metabolite derived from tryptophan, on age-related tissue regeneration and physical decline in zebrafish. Additionally, it examined changes in whole-body mass index (WB-BMI) as an indicator of musculoskeletal aging.

Siblings born in August 2022 were randomly assigned to four groups at age 20 mo: (1) PIC in water (25 mg/kg/day), (2) PIC in water + 25 mg/kg oral gavage, (3) PIC in water + 75 mg/kg oral gavage, and (4) control (system water + gavage) for eight weeks. The treatment groups consisted of 15 fish. At week 7, swimming performance was recorded over a 30-minute period. Caudal fins were amputated for regeneration analysis. In week 8, fish were euthanized for whole-body micro-CT and for β-galactosidase (X-gal) staining to evaluate cellular senescence. The Mann-Whitney U test was used to compare WB-BMI between groups.

Group 2 showed the highest swimming speed (44.5 m/min), followed by Group 1 (34.7 m/min) (p = 0.01 and p = 0.09, respectively) than the control group (31.7 m/min). WB-BMI was decreasing over the duration of the experiment in all 4 groups, with Group 1 maintaining the highest BMD compared to the control (non-significant, p > 0.5). Regeneration in Groups 2 and 3 was more advanced than in Group 1, with stronger staining by β-galactosidase.

PIC at moderate doses supports locomotor function and overall health in aged zebrafish. It may influence regenerative outcomes through mechanisms involving cellular aging.