Effects Of Genetically Modified Probiotics And Exercise On Physical Function In Aged Rats

Abstract

PURPOSE: Declining function in older individuals has enormous clinical and public health consequences, thus therapeutics for preserving function are needed. Advanced age is associated with changes in the gut microbiome, and these changes are associated with functional decline. Our prior work has demonstrated manipulating renin-angiotensin system (RAS) is a promising approach to mitigating age-related functional decline. Recently, genetically modified probiotics (GMP) have also been purported as a promising strategy to deliver drugs with precision and high site specificity. Physical exercise has also been suggested to promote gut health and has important interactions with the Ang(1-7) axis. Here we present preliminary data exploring the impact of oral delivery of genetically modified Lactobacillus paracasei secreting Ang(1-7) [LP-A] and exercise training on physical function in aged rats. METHODS: 24 month old, male F344/BN rats were randomized into 6 groups. They received oral gavage of LP-A, wild-type probiotics (Lactobacillus paracasei), or vehicle 3 times/week; combined with or without exercise for 12 weeks. Exercised rats ran on a treadmill at 12 cm/sec, 10min/day, 5 days/week. Rats in sedentary group were placed on a non-moving treadmill for the same duration of time. After 12 week of intervention, an exercise tolerance test was performed, where all rats were running on a treadmill starting at 12cm/sec for 2 min, then increase by 2 cm/sec each minute until 16 cm/sec was achieved. Running time to exhaustion was recorded. Locomotor tests (open field assay) were also performed. RESULTS: Exercise (mean=1223s) significantly increased time to exhaustion in the exercise tolerance test compared with sedentary animals (mean=464s) in the aged rats. There was also preliminary, but not significant, evidence that LP-A (mean =1329s) group performed best compared to all other exercise groups (Range = 1115-1241s). LP-A increased overall physical activity, compared with all other groups, as measured by the total distance travelled and velocity in the open field test. CONCLUSION: Preliminary findings suggest exercise and LP-A increase physical function in aged male rats respectively, but not synergistically.