Exercise, Health & Genetics Lecture Flashcards

Learning Objectives of Exercise, Health & Genetics

• Describe the pivotal role genetics plays in modern Sports Science and Health research regarding both athletic performance and general health outcomes.

• Discuss the specific impact of exercise on health and the methodologies used to assess these impacts.

• Demonstrate a technical understanding of Single Nucleotide Polymorphisms (SNP) and genetic mutations.

• Discuss the complex interactions between genes and the environment and their combined impact on human performance.

The Comparison of Modern Medicine and Exercise/Diet

• Professors Stephen Harridge and Norman Lazarus (King’s College London) provide a critical perspective on modern health:

  • Society has largely avoided the health consequences of physical inactivity by relying on the "crutch" of modern medicine.

  • While pharmaceutical technology is constantly advancing, exercise provides physiological benefits that medicine cannot replicate.

  • There is currently no pharmaceutical drug available capable of protecting against the loss of muscle mass and strength, which remains the primary factor in the loss of physical function as humans age.

Research Case Study: Counteracting Overfeeding and Inactivity

• Study Title: "Exercise counteracts the effects of short-term overfeeding and reduced physical activity independent of energy imbalance in healthy young men" (Walhin, Richardson, Betts, and Thompson; J Physiol, 2013).

• Central Hypothesis: Determining if daily exercise can mitigate the negative health effects of overfeeding and under-activity, even when it does not fix the energy surplus.

• Experimental Groups:

  • Surplus Group ($n=14$): Subjected to $+50\%$ overfeeding and restricted to less than $4000$ steps per day.

  • Surplus + Exercise Group ($n=12$): Subjected to $+75\%$ overfeeding and restricted to less than $4000$ steps per day but included $45$ minutes of daily vigorous-intensity running.

• Metabolic Findings:

  • Short-term positive energy balance (overfeeding/inactivity) resulted in impaired metabolic outcomes and the alteration of gene expression in adipose (fat) tissue related to nutritional balance and insulin action.

  • Vigorous exercise maintained insulin sensitivity despite a massive energy surplus of approximately $17,000$ extra $kcal$ per week (roughly $2500\,kcal$ per day).

  • Statistical significance: A day $\times$ group interaction was observed ($P=0.002$), with significant pre-post differences in the SUR group ($P=0.001$).

• Adipose Tissue and Gene Expression:

  • Exercise maintained healthy gene expression in adipose tissue even while the tissue was expanding.

  • Serum Adiponectin: Decreased in the Surplus group but was preserved by exercise.

  • Serum Leptin: Increased in both groups due to overfeeding (P < 0.001).

Biological Markers and Assessment Techniques

• Blood/Plasma Analysis:

  • ELISA, Daytona, and MesoScale technology for multiplexing analytes.

  • FACS analysis of Peripheral Blood Mononuclear Cells (PBMCs).

  • DNA isolation for genotyping.

  • Measurement of Glycated proteins (AGE).

• Adipose Tissue Analysis:

  • RT-qPCR for gene expression analysis.

  • Ex-vivo culture for secretion profiles.

  • Western Blotting for protein expression.

  • Digestion for insulin stimulation of adipocytes and FACS analysis of the Stromal Vascular Fraction (SVF).

  • RNA sequencing.

• Skeletal Muscle Analysis:

  • Satellite cell isolation.

  • Glycogen measurements.

  • RT-qPCR and Western Blotting.

• Metabolic Monitoring:

  • Continuous glucose monitoring.

  • Urinary glucose and stool sample microbiome analysis.

• Respiratory Exchange Ratio (RER):

  • RER measures the ratio of $VCO_2/VO_2$.

  • An RER greater than $1$ at rest indicates De novo lipogenesis (DNL), the endogenous pathway converting excess dietary starch, sugar, protein, and alcohol into fatty acids.

The Physiology of Inactivity and Glucose Homeostasis

• ESA 60-day Bed Rest Study (Toulouse, France):

  • One of the longest studies performed, requiring $20$ fit young men to remain in bed for $2$ months.

  • Research published by Trim et al. (2023) in Clinical Nutrition.

• Findings on Inactivity:

  • Long-term inactivity significantly increases blood sugar levels even if caloric intake is adjusted downward to avoid weight gain.

  • Average blood sugar increased by $6\%$ during the day and $10\%$ at night.

  • The body's ability to dispose of blood sugar (uptake into muscles) decreased by nearly a quarter ($24\%$).

Physiological Adaptations to Endurance Exercise

• Elite Performance Statistics:

  • Eliud Kipchoge: $1:59:40$ Marathon ($~21\,km/h$; $5.88\,m/s$; $4:34\,min/mile$).

  • Ruth Chepng’etich: $2:09:56$ Marathon ($~19.51\,km/h$; $5.42\,m/s$; $5:00\,min/mile$).

• VO2max Adaptations:

  • Bouchard et al. (1999) HERITAGE study ($n=481$, $~100$ families): Heritability of $VO_2max$ is approximately $47\%$, with maternal heritability at $~28\%$.

  • Hickson et al. (1977): In fairly untrained subjects training $6$ days/week for $40$ min/day, $VO_2max$ can increase by $44\%$ ($0.12\,L/min$ per week).

• Muscle Fiber Adaptations:

  • Trained individuals show $2-3$ times more capillaries per muscle fiber than untrained individuals.

  • Mitochondrial content can increase $2$-fold with training but decreases rapidly with detraining.

  • Mitochondrial function is more closely related to exercise intensity than volume.

  • Increased fat oxidation capacity spares glycogen stores and utilizes Intramuscular Triglycerides (IMTG).

Cellular Memory and Hypertrophy

• Study by Egner et al. (2013): "A cellular memory mechanism aids overload hypertrophy in muscle long after an episodic exposure to anabolic steroids."

• Mechanism:

  • Muscle fibers are multi-nucleated. When muscles grow (overload or steroid use), the number of nuclei increases.

  • In mice, steroid-induced nuclei persisted for $3$ months after drug withdrawal, even after muscle mass returned to normal.

  • When subjected to new overload, these muscles grew by $30\%$ in $6$ days, while control muscles showed insignificant growth.

  • This suggests that early-life training or brief steroid use may have permanent performance-enhancing effects.

Fundamentals of Genetics and DNA

• DNA Structure:

  • Double helix consisting of two nucleotide chains.

  • Guanine pairs with Cytosine ($3$ hydrogen bonds).

  • Adenine pairs with Thymine ($2$ hydrogen bonds).

• Base Classes:

  • Purines: Adenine (A) and Guanine (G), which have double rings of nitrogen and carbon.

  • Pyrimidines: Cytosine (C) and Thymine (T), which have a single ring.

• Organization:

  • The genome is the total genetic information in a cell.

  • A gene is a sequence of DNA nucleotides encoding a polypeptide chain.

  • Humans have $46$ chromosomes (except sperm/egg).

  • DNA is coiled around histones to form nucleosomes.

  • Current estimate: The human genome contains approximately $21,306$ protein-coding genes.

Protein Synthesis Process

• Transcription (Part 1):

  • Helicase (initiator protein) breaks hydrogen bonds to unzip DNA.

  • RNA polymerase uses DNA as a template to create messenger RNA (mRNA).

  • Spliceosomes edit the primary mRNA before it exits the nucleus.

• Translation (Part 2):

  • Occurs in the ribosome.

  • The triplet code (codon) on mRNA matches with the anticodon on transfer RNA (tRNA).

  • Each codon specifies a single amino acid.

  • Phases: 1) Initiation, 2) Strand elongation, 3) Termination (stop signal).

  • The first codon is typically AUG, which codes for Methionine.

• Post-translational Control: Mechanisms like phosphorylation, glycation, acylation, and methylation can alter protein activity after synthesis.

Genetic Variations and Mutations

• Single Nucleotide Polymorphisms (SNPs):

  • Genetic variations occurring at a single position.

  • Impact heart disease, diabetes, and drug efficacy (e.g., fast vs. slow caffeine metabolizers).

• Sickle Cell Disease:

  • Caused by an SNP in the $HBB$ gene (GAG codon changes to GTG).

  • Substitute Glutamate for Valine, changing protein structure.

  • Protective against Malaria: The parasite cannot survive in leaky, faulty sickle cells that are eliminated quickly by the body.

• Cystic Fibrosis:

  • Caused by mutations in the $CFTR$ gene.

  • Specifically, the deletion of $3$ nucleotides leads to the loss of Phenylalanine at the $508th$ position of the protein.

Genetics in Sports Performance

• Polygenic Profile: Performance is not the result of a single gene but a combination of variants (genetic predisposition) interacting with optimal environments.

• Key Performance Genes:

  • ACTN3 (The Speed Gene): Restricted to Type 2 fast glycolytic fibers. The R577X polymorphism (Arginine to Stop codon) leads to deficiency. The XX genotype is associated with lower sprint/power performance.

  • ACE (Endurance): Musicians and mountaineers often possess the "II" allele variant.

  • PPARD (Marathon): Involved in slow-twitch fiber development.

  • CKMM (Cycling): Influences oxygen-to-energy conversion and $VO_2max$ improvement.

  • Myostatin: A myokine that inhibits muscle growth. Mutations (as seen in the "Belgian Blue" or the case of "MacG") result in extreme muscle overgrowth.

Ethical Considerations and Performance Enhancement

• Gene Doping: Defined by WADA as the non-therapeutic use of genetic elements to enhance performance. It is currently prohibited but difficult to detect.

• Questions & Discussion regarding Athlete Intent (Bamberger & Yaeger, 1997):

  • Question: "If you were given a performance-enhancing substance and you would not be caught and win, would you take it?"

  • Response: $98\%$ of elite Olympic athletes answered yes.

  • Question: "If you were given a performance-enhancing substance and you would not be caught, win all competitions for 5 years, then die, would you take it?"

  • Response: More than $50\%$ answered yes.

• Talent Identification: Organizations like UK Sport use physical screening (e.g., height thresholds: Females > 5'10", Males > 6'2" for rowing) which raises questions about the difference between physical vs. genetic screening.

• Ethical Dilemmas:

  • Should gene technology be allowed for injury recovery?

  • Should "genetically modified athletes" be banned or given separate competitions?