Muscle Damage, Fatigue and Circadian Rhythm

Question 1

Circadian Rhythms

Answer 1

• Expression representative of 24-hr fluctuations in the following factors:
  ○ Endogenous (i.e. the “body clock”)
  ○ Exogenous (i.e. ‘zeitgebers’; such as light-dark cycle) factors
  ○ Attributed to a mixture of influences from the external env, sleep-wake cycle + an internal “body clock” (i.e. suprachiasmatic nuclei (SCN))

Question 2

Body Temperature

Answer 2

• Body temp is a suitable indicator of circadian time
• Body temp higher in evening then morning = temp increases as approach later part of the day
• Souissi et al. [1] showed that oral temp could be used to predict occurrence of maximal + minimal values in the circadian rhythm of anaerobic perf
  ○ Look at pattern of temp = see its very similar to the exercise perf, so in terms of mean power = see a very similar type of pattern emerge = same w/ peak + max power

Question 3

The more muscle temp decreases the more muscular perf decreases.

Answer 3

• Greater increase in vertical jump height w/ increasing muscle temp
• W/ higher temps = the perf of the indiv especially in anaerobic type of task is going to be enhanced

Question 4

Possible reasons for improved anaerobic exercise + muscle strength w/ higher body temp=s

Answer 4

• Increase in carb utilisation over fat as a fuel source.
  ○ Can use w/ or without O2
  ○ Fat = not ideal for a high intensity bout as fat molecule takes a lot longer to break down + to use that energy
• Better facilitation of actin-myosin cross-bridge mechanics within the musculoskeletal unit due to:
  ○ increase calcium release from sarcoplasmic reticulum.
  ○ Reduced concentration of inorganic phosphate = by-product of metabolism = causes inhibition of cross-bridge cycling = tends to slow it down + influence amount of Ca2+ released from SR

Question 5

Passive warming

Answer 5

• Although, passive warming (i.e. deep heat or heater) to increase core body + skeletal muscle temp did not completely ablate diurnal variation in repeated sprint perf [4].
• Factors, independent of heat, may regulate circadian exercise perf, particularly in regards to power and/or strength.

Question 6

Rating of Perceived Exertion

Answer 6

• Conflicting results based on RPE during morning versus afternoon/ evening exercise
• During repeated sprints RPE has been found to be lower in the morning [5], evening [6], or no difference during a Wingate test [7].
• Contradictory results of studies are, perhaps, due to differences in exercise protocols + too few testing times during the day.
  ○ View of exercise can also be influenced by chronotype, sleep, stress levels, temperature etc
• RPE useful in conjunction w/ other tools
• If someone has higher RPE in morning than evening = most likely due to time of day = not adaptative change

Question 7

Effects of circadian rhythm on physical performance and skeletal muscle

Answer 7

• Peak short-term maximal perf achieved in afternoon/evening - body temp (amplitudes ranging b/w 3% + 22%).
• How about the circadian effects on muscle fatigue?

Question 8

What is Muscle Fatigue?

Answer 8

Many definitions………..
Our definition is:
* The failure to maintain a required or expected power output
○ Reversible w/ rest
* Origins linked to peripheral and/or central mechanisms.

Peripheral fatigue: Biochemical + ionic changes at the muscle level that could alter contractile process +/or excitation-contraction coupling.

Central fatigue: Decline in motoneuronal output +/or central motor command = motivation tied into central fatigue concept

Question 9

Nicolas et al [8] showed that the diurnal variation in torque (maximal voluntary contraction - MVC) decrease defined 2 phases:

Answer 9

1. 1st to 26th Rep
2. 26th to 50th Rep
   - Based on EMG results (quads) diurnal variation in muscle fatigue during 50 MVC’s reflected:
   * Greater contractile capacity at 18:00 h
   * Higher fatigability at 18:00 h = greater drop off in perf (as look at beginning reps, then final reps = change in torque produced from beginning to end compared to morning exercise)

Question 10

Lericollais et al. [9] showed decrement in muscle power during a 60-second Wingate test defined at 2 phases: (i) first 20 seconds, (ii) 21 to 60 seconds

Answer 10

• Fatigue index (peak power minus minimal power divided by peak power) higher at 18:00
  = higher fatigue index = suggests greater levels of fatigue present
• In the first part of the test, there is something that occurs that allows the generation of greater force or greater power output in the evening compared to the morning
• See that sports w/ really short perf = enhanced?
• Continual activity = not much change whether in evening or morning

Question 11

In the study of Souissi et al. [10], power output was examined at evening compared to morning during a 30-second Wingate test.

Answer 11

• Phase two: Last 15 seconds - no dif b/w morning + evening.
• Greater decrement in power output found at evening.
• Perf differences due to modifications prevailing at the peripheral rather than central level (based on EMG findings).

Question 12

Chtourou et al. [11] examined repeated sprints performed in the morning versus evening.

Answer 12

• Higher power decrement in sprints during evening.

However…….
Other studies have found:
* No differences in Wingate perf in the morning versus evening in trained cyclists [12].
* Greater fatigue in morning than evening during the Wingate test [13].

Question 13

The results (below) from Racinais et al. [14] provides evidence that higher torque and power decrements observed in the afternoon:

Answer 13

• Likely a mathematical/statistical consequence of a greater initial torque or power output in the afternoon as compared to morning
  ○ No greater fatigue in the evening than the morning if we factor in that perf is going to be enhanced in the evening
• Not the result of higher muscle fatigability

Question 14

Biochemical Markers of Muscle Fatigue

Answer 14

• Many biochemical markers of muscle fatigue (e.g., muscle damage, oxidative stress) are time-of-day dependent.
• Biomarkers of cellular damage + leukocytes have been shown to be higher in the evening compared w/ the morning during:
  ○ Repeated sprint exercise [15] - Hammouda et al.
  ○ 30-second Wingate test [16] - Hammouda et al.
• Additionally, Hammouda et al. [17] showed that blood lactate + glucose responses to a Yo-Yo intermittent recovery test were higher in the evening than the morning.
• May indicate a greater anaerobic contribution to energy production (i.e., higher mobilisation of glucose metabolism at this time-of-day).
• Also, could be associated w/ greater anaerobic exercise perf in the evening?

Question 15

meta analysis

Answer 15

• A meta-analysis conducted by Kentiba et al. [18] revealed that the skeletal muscle injury markers including lactate dehydrogenase (LDH), creatine kinase (CK), aspartate aminotransferase (AST), alanine aminotransferase (ALT) and white blood cells (WBC) possess diurnal variations following exercise.
• The reason for the diurnal variations (i.e. higher at PM) following exercise in these markers has remained unclear ?

Question 16

Circadian Clocks

Answer 16

• Central clock: suprachiasmatic nucleus (SCN) of the brain.
  ○ Light is the major entraining factor for the SCN.
• Peripheral clock: skeletal muscle + bone.
  ○ Regulated indirectly by photic stimulation from the central clock in the SCN using neuro-humoral + temp signals + numerous zeitgebers

Question 17

Clock Genes?

Answer 17

• Clock genes are expressed in skeletal muscle + bones of the skeleton + appear to regulate muscular or bone (osseous)- specific biological function.
• Circadian rhythms in skeletal muscle + bone maintain their homeostasis
• Disturbances of circadian rhythms by social or environmental factors, such as shift work, may result in dysfunctions of skeletal muscle + bone.
• We have genes that are going to be normally expressed within certain periods of time + when we disrupt that = is going to have an effect on how the body regulates itself

Question 18

CLOCK + BMAL1 genes

Answer 18

• Circadian rhythms generated through a translational-transcriptional feedback-loop mechanism, in which circadian locomotor output cycles kaput (CLOCK) + brain + muscle aryl hydrocarbon receptor nuclear translocator-like 1 (BMAL1) proteins (receptors to do w/ brain + muscle)
• CLOCK:BMAL1 also contributes to the expression of a large number of genes, called clock-controlled genes (CCGs)
• Zhang et al. [20] found that skeletal muscle expresses ~1600 circadian genes + that more than 40% of all mammalian protein-coding genes are expressed rhythmically somewhere in the body
• The role of the clock for expression of genes is important for the daily maintenance of skeletal muscle.
• Rhythmic + CLOCK-driven pathways in human skeletal muscle affect ~8% of muscle genes [21]

Question 19

Health and Clock Genes

Answer 19

• People w/ type 2 diabetes + obesity are known to have poor sleep quality [22, 23].
• These conditions may disrupt the core clock machinery [24].
• Ageing is associated w/ a gradual increase in period length of core clock genes, in addition to the dysregulation of other rhythmic biological processes [25].
• Exercise is known to reset clock genes in skeletal muscle + other tissues = timed exercise MAY help to reset the daily clock + improve pathologically deteriorating circadian rhythms
• A functional biological circadian clock is also essential to the normal secretion of basal myokines in vitro such as interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), + monocyte chemoattractant protein-1 (MCP-1) (Perrin et al., 2015)
• Collectively, these findings show that disruptions in the skeletal muscle molecular circadian clock are strongly associated w/ altered muscle structure, function, + metabolic responses that directly affect overall health

Question 20

Importance of Skeletal Muscle Clock

Answer 20

• Skeletal muscle (~40% or more of body mass), important for maintenance of whole-body energy, substrate metabolism, + glucose homeostasis.
• Circadian misalignment in humans results in disturbed energy metabolism + insulin resistance in skeletal muscle [26].
• Regulates protein synthesis + protein degradation.
  ○ Sleep essential for recovery + to build muscle
• Displayed circadian oscillation in genes involved in muscle contraction/growth [27, 28].

Question 21

MICE

Answer 21

• BMAL1 knockout mice + CLOCK mutant mice show disrupted skeletal muscle myofilament architecture (including decreased expression of the myofibrillar proteins Actin, Myosin, and Titin), fibre-type shifts, decreased mitochondria volume, impaired mitochondrial respiration, + decreased muscle strength at the single-fibre level [29, 30].

^^when don’t have BMAL1 or CLOCK genes

Question 22

BMAL1 activation

Answer 22

• Functional muscle clock allows direct BMAL1-dependent activation of genes promoting favourable responses.
• Muscle clock disruption causes loss of BMAL1-dependent activation + REV-ERB-dependent repression of target genes = catabolic conditions = increases = is bad

Question 23

Circadian Rhythm Regulates Protein Synthesis and Protein Degradation

Answer 23

• Acute bout of resistance exercise –> express the IGF-1 –> cascade that goes down to mTOR –> have p70S6K –> protein synthesis –> will block any muscle atrophy or protein translation = good thing = muscle is being stimulated + leading to adaptations favourable to an individual
• When we see there is a block of the BMAL1= leads towards factors that impair the ability of the chain of events = therefore it inhibits mTOR –> produces expression of genes that lead towards degradation of protein

Question 24

Circadian Rhythm: Effects of Diet and Exercise

Answer 24

• Diet + exercise represent two major interventions that can suppress the atrophy of skeletal muscle, + have regulatory roles in circadian rhythm.
• Along w/ other zeitgebers are natural phenomena that can affect the circadian rhythm.
  ○ [31] Zhang et al.

Question 25

Circadian Rhythm and Timing of Exercise

Answer 25

• Evidence that exercise-induced contraction + its timing may regulate gene expression + protein synthesis related to muscle anabolism + metabolism [32, 33].
• Importance of “circadian phenotype” on optimal aerobic exercise perf [34], but little research on resistance exercise perf
• Phenotype refers to an individual’s observable traits, such as height, eye colour + blood type. A person’s phenotype is determined by both their genomic makeup (genotype) + environmental factors.

Question 26

Summary

Answer 26

• Circadian rhythm of core temp is associated w/ anaerobic exercise perf + muscle strength.
• Other factors independent of heat may regulate circadian exercise perf
• Perceived effort during morning versus evening exercise seems to be unaffected - but may differ when considering factors (e.g. chronotype).
• Muscle perf decrement occurs during evening compared to morning exercise - linked to higher perf in evening.
• Greater muscle damage appears following evening exercise.
• Clock genes regulate muscle + bone function.
• Skeletal muscle clock important for contraction + growth.
• Exercise + diet are important factors that can influence the expression of skeletal muscle clock genes