The Physiology Behind Athletic Improvement.

Apply a physical stress to a biologic system and it adapts and improves, that's the rationale for all athletic training. With interval training, pushing an athlete's aerobic limits leads to changes in the cardiovascular system and muscle cells that mean they can push even harder the next time out.

This is a dynamic process. Changes reverse if the physical stress is removed. Luckily maintaining improvement does not require as much "stress" as the development of the increased capability in the first place. But it is true that you need to "use it or lose it". So on that business trip, or family vacation, it is worth taking the time for a short (30 to 60 minute) brisk walk that will boost your heart rate.

Exercise induced changes can be seen at three levels.

At the cell level.

• Mitochondria, the powerhouses of the muscle cell, increase in both size and number in response to interval training which means more ATP to power the exercising muscle.

  This reference focuses on nerve cells, but there is almost certainly a similar SIRT3 based process in mitochondria throughout the body. To quote: "Researchers ....discovered that an enzyme called SIRT3 that is located inside mitochondria may protect mice brains from loss of their energy supply (Cell Metabolism, November 19, 2015). Normal mice who ran on a spinning wheel increased their levels of SIRT3 in nerve cells, maintained brain function with aging ..... A special group of mice that were genetically engineered to be unable to produce SIRT3 gained no benefit from running on a spinning wheel..... This implies that SIRT3 strengthens brains and that blocking SIRT3 prevents exercise from benefiting brain function."

• We know that exercise has a direct effect on our chromosomes to inhibit telomere shortening. So it is reasonable to speculate that exercise might up or down regulate other genes which directly impact aerobic metabolism.

The heart size increases which means the amount of blood pumped per beat (the stroke volume) increases with more blood pumped per beat to the lungs and then on to the muscles.

At the organ integration level.

There are body wide changes in the vscular system. The number of capillaries per muscle fiber increases, supporting an increased delivery of oxygen (from the increased cardiac output) to individual muscle cells (which now have the mitochondrial capacity to increase ATP production.)

What is behind these chnages. How are they coordinated i.e. how do the cells and physiologic systems improve in parallel? Two possibilites are:

1. Neurologic signals. These signals might originate at the spinal cord level or a more central cerebral level. A central governor coordinating all the systems involved in meeting increased physiologic demands is an example.

2. Molecular signals. The traditional teaching was aerobic training stress lead to individual, cell specific improvements. An anaerobic state developed in the muscle cell which in turn led to adaptive changes in that specific cell's mitochondria to improve performance. But we now know that thousands of potential molecular signals are distributed to every cell at the same time.

   This NYT article explains how exercise changes the Metabolome - the set of metabolites (organic molecules) in a cell, tissue, organ or organism, which are involved in cellular metabolism. 9,815 - or more than half - changed after exercise. The explanation of positive training effects is almost certainly buried in this collection of 9815 organic molecules.

   How can molecules that make up the metabolome travel in the bloodstream without being degraded? They are packaged in small protected packets (vesicles) as explained in this original investigation (more easily understood in this NYT article.

   There is also evidence that the microbiome is indirectly involved. Regular aerobic training changes the microbiome. These bacteria metabolize unabsorbed food material from our diet (generally fiber) and as a byproduct of their metabolism manufacture short chain fatty acids (SCFA). The SCFA (which are absorbed from the colon) impact mitochondrial development and body wide energy metabolism.

   This article puts forth a good argument for part some of the aerobic performance being indirectly via the microbiome. Exercise --> changes in bacteria --> production of molecules that will positively influence mitochondrial metabolism and growth.

Is there a difference? Male versus female endurance physiology.

In untrained individuals, a metabolic difference in cell energy production favors female athletes over untrained men, but this metabolic advantage diminishes with training at which point VO2max and muscle mass provide the men their advantage in shorter events. But it may be these underlying metabolic differences then explain the resurgence in women's performances as distances and duration increase.

What are the metabolic differences? In 16 subjects, muscle biopsies were profiled for patterns of three sets of omics data - DNA methylation for insight into genes switched on and off (epigenomics), RNA molecules transcribed from genes (transcriptomics), and proteins (proteomics). Significant sex-specific differences were observed in 120 proteins (as well as methylation sites of 16,012 genes and 1366 RNA transcripts).

Men displayed a higher abundance of glycolysis-related proteins and other fast-twitch fiber type proteins involved in the processing of glucose, while women showed more proteins responsible for regulating fatty acid metabolism. But after an 8 week exercise regimen, these differences significantly diminished.