Endurance Exercise and Selective Breeding for Longevity Extend Drosophila Healthspan by Overlapping Mechanisms

Abstract

Endurance exercise has emerged as a powerful intervention to extend healthy physiology into advanced age. Normal, age‐associated declines in organ structure and function are alleviated in endurance‐trained individuals. Long‐term exercise also reduces age‐related pathologies. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare the effects of endurance training on Drosophila melanogaster to the effects of selective breeding for longevity. We find that both selective breeding and endurance training increase endurance, cardiac performance, running speed, flying height, and levels of autophagy in adipose tissue. Microarrays indicate that 73% of transcriptional changes found in flies selectively bred for longevity are also found in flies subjected to three weeks of exercise training. Both endurance training and longevity selection upregulate folate biosynthesis, stress defense and lipid metabolism. Conversely, both interventions downregulate multiple carbohydrate metabolism pathways. methuselah‐like 3 was also transcriptionally reduced in both groups. Altering mthl3 expression in adult flies was able to reproduce a subset of the shared phenotypes. These results provide support for endurance exercise as a broadly acting anti‐aging intervention and confirm that exercise training acts in part by targeting longevity assurance pathways. In addition, these results identify the mthl3 gene as a potential target of exercise training.