Endurance Exercise and Selective Breeding in Fly Longevity

The paper linked below looks at overlaps in the underlying mechanisms by which exercise and selective breeding can extend fly life spans, and is typical of much of the mainstream of aging research these days. A great deal of the field still involves finding natural ways to extend life and then digging through the biochemistry to gain more knowledge of its operational parameters. It is all very interesting, but we shouldn't expect these research programs to result in methods of significantly extending life in humans; the goal here is understand the relationship between the enormously complex operation of metabolism and natural variations in life span.

Aging is damage, and so natural variations in life span relate to the pace at which damage accumulates over time. Since living organisms self-repair, this is not a straightforward process, and there is room for decades of research yet for those interested in the fine details of every part of the downward spiral. In many ways a damaged, old metabolism is even more complicated that the correctly functioning younger version. When the research community does get around to building meaningful rejuvenation therapies, such as those detailed in the SENS proposals, they will not be created atop the knowledge of how metabolism determines longevity. The goal will be to halt and reverse degenerative processes through damage repair rather than trying to alter metabolism to slightly slow down the pace of damage accumulation. The nature of that damage and how to repair it are already well known, and the work left is to build the necessary technologies. How exactly damage spirals out to create dysfunction is a big empty space on the map, but if the damage can be repaired then researchers don't need that knowledge in order to create rejuvenation therapies.

Endurance exercise has emerged as a powerful intervention that promotes healthy aging by maintaining the functional capacity of critical organ systems. In addition, long-term exercise reduces the incidence of age-related diseases in humans and in model organisms. Despite these evident benefits, the genetic pathways required for exercise interventions to achieve these effects are still relatively poorly understood. Here, we compare gene expression changes during endurance training in Drosophila melanogaster to gene expression changes during selective breeding for longevity. Microarrays indicate that 65% of gene expression changes found in flies selectively bred for longevity are also found in flies subjected to three weeks of exercise training.

We find that both selective breeding and endurance training increase endurance, cardiac performance, running speed, flying height, and levels of autophagy in adipose tissue. Both interventions generally upregulate stress defense, folate metabolism, and lipase activity, while downregulating carbohydrate metabolism and odorant receptor expression. Several members of the methuselah-like (mthl) gene family are downregulated by both interventions. Knockdown of mthl-3 was sufficient to provide extension of negative geotaxis behavior, endurance and cardiac stress resistance. 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.

Link: http://www.impactaging.com/papers/v7/n8/full/100789.html

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