Skeletal Muscle Ageing LT4 Flashcards
What types of skeletal muscle do humans have?
Type 1, 2a and 2x
Type 2b is found in rodents, NOT humans
What are the qualities of the different types of muscle found in humans?
Type 1 (oxidative) = aerobic respiration, mainly rely on fat as fuel, conserving glycogen for more intense activities
Type 2a (oxidative) = aerobic and anaerobic metabolism of fats and carbohydrates
Slower twitch than 2x but more fatigue resistance
Type 2x (glycolytic) = primarily relies on anaerobic metabolism, using glycogen for quick bursts of energy
Rapid fatigue due to accumulation of lactic acid and depletion of glycogen
Which muscle type has the lowest succinate dehydrogenase activity in humans and why?
Type 2x
SDH is an enzyme involved in the citric acid cycle and is an indicator of aerobic metabolism.
Since Type 2x fibres primarily rely on anaerobic metabolism for energy production, they exhibit lower levels of SDH compared to Type 1 and Type 2a fibres, which are more oxidative and better suited for aerobic activities.
What determines our biolgoical age?
Vascular age
How is lean mass measured?
DXA (Dual X-ray Absorptiometry) uses low dose X-rays to analyse distribution of fat, muscle mass and bone in the body
How is strength measured?
Isokinetic knee extensor strength
How does muscle mass affect strength?
Even if you gain or maintain muscle mass, the strength is not necessarily kept
What do neurones and muscle fibres have in common?
They are both post-mitotic
What is the advantage of having multiple nuclei in one myofibre?
If one fails, then others can compensate
Name 3 types of myonuclei, and where they are found?
Active myonuclei newly differentiated from satellite cells
Myonuclei in healthy, undamaged adult myofiber lie along the periphery of myofiber, just under sarcolemma
After myofiber damage, central nuclei appear indicating the myofiber has undergone degeneration and regeneration events
What do mature myonuclei look like?
Flat
Active myonuclei newly differentiated from satellite cells are not flat
What improves our quality of muscle?
The number of good quality sarcomere
The more sarcomere theoretically generates greater contractile force because more cross-bridges can occur
What is the conventional strategy targeting age-related loss of muscle mass?
Increase anabolism and hypertrophy by drinking more amino acids/proteins
Assumption: when protein synthesis rate is higher than protein degradation = muscle hypertrophy
What macromolecule can not be stored in our cells?
Proteins = only made when they are needed
Carbs = stored as glycogen
Lipids = stored as triglycerides
Nucleic acids = stored in chromosomes
How is sustained anabolic stress caused?
Prolonged resistance training or anabolic hormones
Name two anabolic hormones
Testosterone
IGF-1
What occurs under sustained anabolic signalling?
Increased proteostasis stress and increase mTOR because more protiens need o be made
Proteostasis stress = stain placed on cell’s protein synthesis, folding and degradation system
What is proteostasis?
Protein homeostasis = balance and regulation of protein synthesis, folding, trafficking, and degradation within a cell
It ensures that proteins maintain their proper structure and function, preventing aggregation and misfolding that can lead to cellular stress and diseases such as neurodegeneration and cancer
Proteostasis involves molecular chaperones, proteasomes, and autophagy, which work together to manage protein quality control.
How does increased anabolism lead to increased misfolding, and what is the outcome?
High protein demand can put a strain on proteostasis network, causing increased misfolding
Increased misfolding, then leads to increased autophagy and ubiquitin-proteasome system (UPS)
How are prolonged anabolic stress and autophagy related?
Anabolic stress increases rate of faulty protein production, leading to increased degradation by autophagy
Why is looking at the bulk size of muscle not accurate in telling the muscle percentage?
Because having bigger mass could be due to glycogen or lipid storage
What energy sources do the muscle types use?
Type 1 OXIDATIVE= use oxidation via mitochondria as major energy source to generate 36ATP (aerobic respiration)
Type 2x GLYCOLYTIC = use glucose, only generates 2ATP in cytoplasm (anaerobic respiration)
Where are muscle stem cells found?
Satellite stem cells nestle where blood vessels meet the skeletal muscle
This is their NICHE
Why are there more satellite cells in Type I muscle fibre?
Because Type 1 has a higher capillary density than Type 2 fibre
What happens to Type 2 muscle fibre as our vascular system ages?
Vascular damage occurs and because Type 2 have less capillary density to start with there is a dramatic reduction of satellite cells in Type 2 fibres
How does innervation increase contraction?
More innervated myofibers means more can contract simultaneously
Explain the motor nervous system
Voluntary movements are generated in the brain as motor commands
They pass down the spinal cord (CNS) and out through motor neurones (PNS)
Sensory feedback from the muscles and joints informs the brain about the movement, allowing for adjustments if needed
What is sarcopenia?
Age-related loss of muscle mass, strength, and function
Characterized by a decline in muscle fibres, particularly the fast-twitch fibres responsible for quick, powerful movements
What process do they use to diagnose sarcopenia?
If there is clinical suspicion, or they score low in the questionnaire, then grip strength is measured
If that is low then muscle mass is measured (DXA) this can confirm saropenia
Finally, measure physical performance = gait speed, chair sit 5x, and Timed Up and Go test (TUG)
Which can confirm severe sarcopenia
What does the Timed Up and Go test assess?
Functional mobility, including:
Balance
Walking ability
Fall risk in the elderly
What does BCA measure?
Body composition analysis to look at muscle mass
In a clinical trial, what factors must we take into account?
Age, Sex, Race, Occupation, Dominant hand
Injury history and machine measuring difference
What is the benefit of Type 1 being able to be innervated instead if there is an innervation issue with motor neurone Type 2?
Type II muscle fibers can undergo a process called “innervation switching,” where they adapt to changes in motor neuron input.
When fast-twitch fibers lose their innervation or experience motor neuron damage, adjacent motor neurons may reinnervate these fibers, potentially converting them to a slower, more fatigue-resistant phenotype.
This process is facilitated by the plasticity of muscle fibers and the ability of satellite cells to support repair and remodeling. As a result, Type II fibers may take on characteristics similar to Type I fibers, enhancing endurance and resilience under altered functional demands.
How does Bioelectrical Impedance Analysis (BIA) work and what dose it measure?
Weak electric current flows through body
Voltage is measured to calculate resistance and reactance of body
BIA measures total body water from which lean body mass is calculated using assumption all tissues have same degree of hydration
Where is the most body water stored?
Muscle
How does Dual-energy X-ray Absorptiometry (DXA) work and what dose it measure?
Uses low dose X-ray
Analyses distribution of fat, muscle mass and bone in the body
What does Computed Tomography (CT) measure?
Specialized X-ray equipment to produce cross-sectional images of the body
How does MRI work and what does it measure?
No exposure to radiation
Images the soft-tissue structures of the body = muscle, bones and joints
Often clearer and more detailed than with other imaging methods
How does Quantitative Magnetic Resonance (QMR) work and what does it measure?
Magnetic field strength of main magnet is much lower than MRI
Generates information based on radiation frequencies
How do we measure muscle health?
Measuring muscle strength is the easiest quantifiable way to measure muscle health
Measure knee extensor strength
Muscle quantity does not reflect its QUALITY
How does the ultrastructure change in skeletal muscle with age?
Reduced satellite cell pool
Fibre loss = rare because so many nuclei
Fibre atrophy = common due to other factors, protein aggregates and mitochondrial damage
Intramuscular fat
Fibrosis
Denervation
Capillary attrition
What is the difference between fibre loss and fibre atrophy?
Muscle fiber loss involves a reduction in the total number of muscle fibers. This can occur due to various factors, such as aging, injury, or certain diseases. Conditions like muscular dystrophy or prolonged immobilization can lead to the death of muscle fibers, resulting in fewer fibers overall.
Muscle fiber atrophy, on the other hand, refers to a decrease in the size of existing muscle fibers rather than a reduction in their number. This can occur due to disuse (like sedentary lifestyles), aging, or hormonal changes. Atrophy can be reversible with proper exercise and nutrition.
Muscle fiber atrophy is generally more common, especially in older adults or those who are less active. While muscle fiber loss can occur, it typically happens under specific pathological conditions or prolonged disuse. In many cases, muscle atrophy can be addressed through targeted exercise and nutrition, while fiber loss may require more complex interventions.
What do we look at when studying myofibre health?
Look at the shape, are they a regular honeycomb shape?
Cannot look at number of myofibres because people have different densities of muscle fibres depending on their size
Why does intramuscular fat disrupt the muscular coordination?
Because it disrupts their connection and communication
Shown in diabetic and obese patients
Describe age-related changes in type 1 and type 2 composition
As we age Type 1 fibres become more clustered
We lost Type 2 fibres much more than Type 1
So Type 1 fibre increases to compensate for that
Type 2 atrophies and Type 1 hypertrophies
Missense vs Nonsense mutation
Missense = a single nucleotide change results in the substitution of one amino acid for another in a protein sequence
Nonsense = a single nucleotide change converts a codon that originally codes for an amino acid into a stop codon. This premature stop codon leads to the truncation of the protein during translation, resulting in a shorter, often nonfunctional protein
What mutation do the Piedmontese have?
Myostatin sequence contains a missense mutation in exon 3
Results in substitution of Tyr for invariant Cys in mature region of protein
How does the myostatin mutation change the Piedmontes’s phenotype?
Myostatin is a protein that normally inhibits muscle growth.
When it is mutated, its function is disrupted, leading to increased muscle mass and reduced fat deposition
This mutation results in a condition known as double muscling, where the animals exhibit larger, more developed muscles compared to typical cattle. The enhanced muscle growth makes Piedmontese cattle particularly valued for their lean meat, as they produce more muscle tissue with less fat.
What is associated in children with the myostatin mutation?
Gross muscle hypertrophy in children = associated with myostatin mutation
Absence of mature myostatin means that there is less inhibition of muscle growth
How does myostatin affect mTOR?
Myostatin negatively regulates muscle growth by inhibiting the mTOR, which is crucial for protein synthesis and muscle hypertrophy
Why have myostatin inhibitors failed?
Because factors were not controlled
And trials in mice were not acurrately reflectd in humans
