VO2max, aerobic potential

Respiratory capacity

One of the key determinants of endurance performance is the maximal oxygen uptake (aka VO2max). It is widely considered as the single best indicator of aerobic physical fitness. VO2max potential is highly genetic, with evaluated genetic contribution of up to 60%. Most of this contribution is in genetic variation related to the efficiency of mitochondrial biogenesis.

 

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In order to produce energy, oxygen must reach the mitochondria, the 'power houses' of each of the body's cells. The pathway for oxygen from the atmosphere to the mitochondria depends mainly on the abilities of the lungs, heart and blood each of which could represent a potential impediment to O2 flux. The indicator known as VO2max is the most common method to evaluate the cardiorespiratory system ability to transport O2 to the muscles during intensive effort.

VO2max stands for maximal oxygen uptake and refers to the amount of oxygen your body is capable of       utilizing in one minute. It is a measure of your capacity for aerobic work and can be a predictor of your potential as an endurance athlete

Gene: PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR-GAMMA, COACTIVATOR 1, ALPHA (PPARGC1A)

Genomic coordinates (GRCh38): 4:23,792,020-24,472,974

 

PPARGC1A is a crucial component in training-induced muscle adaptation. Its levels affecting oxygen utilization and time-to-fatigue. The PPARGC1A protein activates transcriptional factors that control glucose and lipid transportation and oxidation, skeletal muscle fiber-type formation, and mitochondrial biogenesis.

Exercise increases PPARGC1A levels, which leads to improved oxygen utilization and resistance to muscle fatigue.

Among untrained individuals, the variant form of the PPARGC1A gene was found associated with higher base VO2max rate, better oxygen utilization, fitness and aerobic ability . Variant carriers are naturally closer to their best VO2max, while others would require more aerobic training to improve and maximize their VO2max.
 

Among highly trained individuals, factors other the PPARGC1A gene set-up constrict improvement in stamina. However, PPARGC1A genotype can predict how fast will aerobic fitness drop following a period of no or little training, and how fast would an athlete reach back to his optimal VO2max values.

Meta-analysis studies find that the frequency of the PPARGC1A G variant is enriched among Caucasian endurance athletes, which implies that the G variant is advantageous for endurance performance.

Gene: GA-BINDING PROTEIN TRANSCRIPTION FACTOR, BETA SUBUNIT (GABPB1),                                    NUCLEAR RESPIRATORY FACTOR 2 (NRF2)

Genomic coordinates (GRCh38): 15:50,277,191-50,355,428

The NRF2 protein improves respiratory capacity and increases the rate of ATP production during exercise. This is due to its important role in inducing mitochondrial biogenesis.

 

The mitochondria are 'power houses' found in every body cell, producing energy in the form of ATP. 

Mitochondrial biogenesis (mitochondriogenesis) is the process of producing more bodies of mitochondrion in muscle cells. This usually happens in response to exercise and greater demand for energy by the muscle. 

Mitochondrial biogenesis is initiated by the pivotal PPARGC1A gene, while NRF2 is an intermediate transcription factor needed for activating the replication of mitochondrial DNA molecules. Owing to the key role that the PPARGC1A-NRF pathway plays in aerobic exercise phenotypes, genetic variants of this pathway are associated with the attainment of elite endurance status.

The NRF2 gene also regulates several nuclear genes encoding mitochondrial proteins, including cytochrome c and TFAM, as well as regulating heme biosynthesis proteins.

The distribution frequency of the NRF2 A variant was found significantly higher in endurance-oriented athletes than in sprinters, or in untrained controls.  

Frequency of the A allele is lower both in power athletes and non-athletes. Since the NRF2 variant frequency is enriched among endurance athletes, it is a strong candidate to predict success in aerobic sports.

The AA genotype was highly associated with endurance athletes and therefor is probably favorable for endurance performance.