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Human Ageing > Skeletal Muscle Ageing LT4 > Flashcards

Skeletal Muscle Ageing LT4 Flashcards

1
Q

What types of skeletal muscle do humans have?

A

Type 1, 2a and 2x

Type 2b is found in rodents, NOT humans

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2
Q

What are the qualities of the different types of muscle found in humans?

A

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

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3
Q

Which muscle type has the lowest succinate dehydrogenase activity in humans and why?

A

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.

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4
Q

What determines our biolgoical age?

A

Vascular age

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5
Q

How is lean mass measured?

A

DXA (Dual X-ray Absorptiometry) uses low dose X-rays to analyse distribution of fat, muscle mass and bone in the body

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6
Q

How is strength measured?

A

Isokinetic knee extensor strength

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7
Q

How does muscle mass affect strength?

A

Even if you gain or maintain muscle mass, the strength is not necessarily kept

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8
Q

What do neurones and muscle fibres have in common?

A

They are both post-mitotic

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9
Q

What is the advantage of having multiple nuclei in one myofibre?

A

If one fails, then others can compensate

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10
Q

Name 3 types of myonuclei, and where they are found?

A

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

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11
Q

What do mature myonuclei look like?

A

Flat

Active myonuclei newly differentiated from satellite cells are not flat

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12
Q

What improves our quality of muscle?

A

The number of good quality sarcomere

The more sarcomere theoretically generates greater contractile force because more cross-bridges can occur

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13
Q

What is the conventional strategy targeting age-related loss of muscle mass?

A

Increase anabolism and hypertrophy by drinking more amino acids/proteins

Assumption: when protein synthesis rate is higher than protein degradation = muscle hypertrophy

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14
Q

What macromolecule can not be stored in our cells?

A

Proteins = only made when they are needed

Carbs = stored as glycogen
Lipids = stored as triglycerides
Nucleic acids = stored in chromosomes

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15
Q

How is sustained anabolic stress caused?

A

Prolonged resistance training or anabolic hormones

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16
Q

Name two anabolic hormones

A

Testosterone
IGF-1

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17
Q

What occurs under sustained anabolic signalling?

A

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

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18
Q

What is proteostasis?

A

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.

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19
Q

How does increased anabolism lead to increased misfolding, and what is the outcome?

A

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)

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20
Q

How are prolonged anabolic stress and autophagy related?

A

Anabolic stress increases rate of faulty protein production, leading to increased degradation by autophagy

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21
Q

Why is looking at the bulk size of muscle not accurate in telling the muscle percentage?

A

Because having bigger mass could be due to glycogen or lipid storage

22
Q

What energy sources do the muscle types use?

A

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)

23
Q

Where are muscle stem cells found?

A

Satellite stem cells nestle where blood vessels meet the skeletal muscle

This is their NICHE

24
Q

Why are there more satellite cells in Type I muscle fibre?

A

Because Type 1 has a higher capillary density than Type 2 fibre

25
Q

What happens to Type 2 muscle fibre as our vascular system ages?

A

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

26
Q

How does innervation increase contraction?

A

More innervated myofibers means more can contract simultaneously

27
Q

Explain the motor nervous system

A

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

28
Q

What is sarcopenia?

A

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

29
Q

What process do they use to diagnose sarcopenia?

A

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

30
Q

What does the Timed Up and Go test assess?

A

Functional mobility, including:
Balance
Walking ability
Fall risk in the elderly

31
Q

What does BCA measure?

A

Body composition analysis to look at muscle mass

32
Q

In a clinical trial, what factors must we take into account?

A

Age, Sex, Race, Occupation, Dominant hand

Injury history and machine measuring difference

33
Q

What is the benefit of Type 1 being able to be innervated instead if there is an innervation issue with motor neurone Type 2?

A

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.

34
Q

How does Bioelectrical Impedance Analysis (BIA) work and what dose it measure?

A

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

35
Q

Where is the most body water stored?

A

Muscle

36
Q

How does Dual-energy X-ray Absorptiometry (DXA) work and what dose it measure?

A

Uses low dose X-ray

Analyses distribution of fat, muscle mass and bone in the body

37
Q

What does Computed Tomography (CT) measure?

A

Specialized X-ray equipment to produce cross-sectional images of the body

38
Q

How does MRI work and what does it measure?

A

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

39
Q

How does Quantitative Magnetic Resonance (QMR) work and what does it measure?

A

Magnetic field strength of main magnet is much lower than MRI

Generates information based on radiation frequencies

40
Q

How do we measure muscle health?

A

Measuring muscle strength is the easiest quantifiable way to measure muscle health

Measure knee extensor strength

Muscle quantity does not reflect its QUALITY

41
Q

How does the ultrastructure change in skeletal muscle with age?

A

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

42
Q

What is the difference between fibre loss and fibre atrophy?

A

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.

43
Q

What do we look at when studying myofibre health?

A

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

44
Q

Why does intramuscular fat disrupt the muscular coordination?

A

Because it disrupts their connection and communication

Shown in diabetic and obese patients

45
Q

Describe age-related changes in type 1 and type 2 composition

A

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

46
Q

Missense vs Nonsense mutation

A

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

47
Q

What mutation do the Piedmontese have?

A

Myostatin sequence contains a missense mutation in exon 3

Results in substitution of Tyr for invariant Cys in mature region of protein

48
Q

How does the myostatin mutation change the Piedmontes’s phenotype?

A

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.

49
Q

What is associated in children with the myostatin mutation?

A

Gross muscle hypertrophy in children = associated with myostatin mutation

Absence of mature myostatin means that there is less inhibition of muscle growth

50
Q

How does myostatin affect mTOR?

A

Myostatin negatively regulates muscle growth by inhibiting the mTOR, which is crucial for protein synthesis and muscle hypertrophy

51
Q

Why have myostatin inhibitors failed?

A

Because factors were not controlled

And trials in mice were not acurrately reflectd in humans

Human Ageing (10 decks)

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