Skeletal Muscle Function & Skeletal Muscle in Ageing and Disease

Question 1

Muscles with which characteristics fatigue more easily?

Answer 1

Larger, faster muscle fibres

Question 2

Muscles with which characteristics are more fatigue resistant?

Answer 2

Smaller, slower muscle fibres

Question 3

What are the characteristics of the vast variety of muscle fibres between fast-twitch and slow-twitch fibres?

Answer 3

Intermediate speed

Don’t fatigue as easily

Question 4

What is muscle fibre malleability?

Answer 4

Muscles adapt to stimuli

Question 5

What is the makeup of muscle fibres based on their type of myosin?

Answer 5

Either pure = have one type of myosin, or as hybrids containing multiple forms

Question 6

How is lifespan/healthspan extension possible?

Answer 6

Targeting detrimental effects of ageing, including

• Healthy lifestyle
• Actionable/drug-treatable molecular targets

Question 7

What does frailty and weakness confer a high risk of?

Answer 7

Mortality
Falls
Institutionalisation
Hospitalisation

Question 8

What is sarcopenia?

Answer 8

Age-associated loss of skeletal muscle mass and function

Question 9

What is the rate of loss of muscle mass after the age of 50?

Answer 9

1-2%

Question 10

What is cachexia?

Answer 10

Generalised wasting of muscle and fat, typically associated with tumours

Question 11

Are sarcopenia and cachexia the same?

Answer 11

Cachexia may be component of sarcopenia but not same thing

Question 12

Is sarcopenia affected by health behaviours?

Answer 12

Independent of them, but good ones may slow down rate

Question 13

In whom should sarcopenia be considered?

Answer 13

Patients who

• Are bedridden
• Can’t independently rise from chair
• Have gait speed <1 m/s

Question 14

How is sarcopenia diagnosed?

Answer 14

Gait speend of <1 m/s and appendicular lean/fat ratio is less than 2 standard deviations young adult

Question 15

What is the effect of age on physical performance if you are a marathon runner?

Answer 15

Steady decline after peak at 20-40 years

Question 16

What is the effect of age on physical performance if you are a weight lifter?

Answer 16

More marked decline than marathon runners

Question 17

What is muscle weakness?

Answer 17

Inability to develop initial force appropriate for circumstances

Question 18

When does muscle strength start to decline?

Answer 18

After age 50

Question 19

Which muscle type shows a greater decline in strength with age?

Answer 19

Fast muscles show greater decline than slow muscles

Question 20

What is the impact of loss of muscle strength with age?

Answer 20

Impacts progressively on physical capacity and work performance
Eventually impacts on activities often taken for granted

Question 21

What happens if protein synthesis outweighs protein degradation in muscle?

Answer 21

Hypertrophy

Question 22

What happens if protein degradation outweighs protein synthesis in muscle?

Answer 22

Atrophy

Question 23

What is dynapenia?

Answer 23

Age-related loss of muscle strength

Question 24

What is the association between muscle weakness and mortality?

Answer 24

Higher mortality in older people, to degree much higher than cohort who only has low lean mass

Question 25

What happens in age-related motor unit remodelling?

Answer 25

Skeletal muscle bundle innervated by type I (slow) and type II (fast) motor units in checkerboard pattern Progressive denervation of type II motor units > fast-twitch fibres reinnervated with type I motor units > fibre becomes slow-twitch > expansion of slow motor unit

Question 26

What happens to the size and strength of muscles with age?

Answer 26

Become smaller | Strength decreases

Question 27

What happens to movement with age

Answer 27

Become slower and less precise

Question 28

What injuries do you have and increased risk of with age?

Answer 28

Falls | Fractures

Question 29

What increases as muscle mass decreases?

Answer 29

Connective tissue | Fat

Question 30

What molecular change slows muscle contractility with age?

Answer 30

Changes in Ca handling affects speed of contracction

Question 31

How do mitochondria in muscle change with age?

Answer 31

Reduced number | Loss of enzyme content

Question 32

What happens in strength training for the elderly?

Answer 32

Increases muscle strength Increases lean total body mass Increases muscle fibre area Increases quality of life because of increased function

Question 33

If strength training is to be a preventative measure in sarcopenia, when must it be started?

Answer 33

Lifelong commitment > start at younger age

Question 34

What sorts of exercise can help slow the rate of age-related changes in skeletal muscle?

Answer 34

Strength training Aerobic exercise Flexibility Balance

Question 35

How do hormones contribute to age-related changes in skeletal muscle?

Answer 35

Decreased circulating levels of anabolic hormones - Growth hormone - IGF-I - Testosterone Compromises efficiency of muscle regeneration as consequence of daily wear and tear

Question 36

What is muscular dystrophy?

Answer 36

Diverse group of inherited disorders characterised by progressive skeletal muscle weakness and wasting

Question 37

What causes Duchenne muscular dystrophy?

Answer 37

Lack of dystrophin - Complete absence/ - Non-functional protein

Question 38

What is the inheritance pattern of Duchenne muscular dystrophy?

Answer 38

X-linked recessive

Question 39

What is the implication on genetic counselling if one in three cases of Duchenne muscular dystrophy are the result of a new mutation?

Answer 39

Even with genetic counselling, a new mutation can manifest

Question 40

What are the clinical features of Duchenne muscular dystrophy?

Answer 40

3-6 years - gait becomes lordotic and waddling Gowers sign appears Enlargement of calf, gluteal, lateral vastus, deltoid, and infraspinatus muscles Muscles of lower extremity and torso more affected than upper 6-11 years - strength of limb and torso muscles decreases linearly

Question 41

What is Gowers sign?

Answer 41

Can't stand unaided

Question 42

What does the muscle in Duchenne muscular dystrophy look like under the microscope?

Answer 42

Variation in size of muscle fibres | Infiltration by connective tissue and fat

Question 43

Are all muscles affected in Duchenne muscular dystrophy?

Answer 43

Some spared, like extraocular muscles

Question 44

What are the molecular changes to the muscle in Duchenne muscular dystrophy?

Answer 44

Small diameter of fibres Lower mechanical stress per unit surface membrane area Increased sarcolemmal expression of compensatory proteins

Question 45

What is the inheritance pattern of Becker muscular dystrophy?

Answer 45

X-linked recessive

Question 46

What is Becker muscular dystrophy?

Answer 46

Similar to Duchenne, but less severe Manifests later Slower time course

Question 47

What protein is affected in Becker muscular dystrophy?

Answer 47

Dystrophin

Question 48

What is the difference between dystrophin expression in Duchenne and Becker muscular dystrophy?

Answer 48

Duchenne - virtually no dystrophin | Becker - significant amounts of abnormal, smaller molecules

Question 49

What is dystrophin associated with in the cytoplasm?

Answer 49

Tightly associated with series of transmembrane proteins

Question 50

What does dystrophin do in muscle cells?

Answer 50

Transmits force across membrane | Stabilises sarcolemma during muscle contraction, especially lengthening actions

Question 51

What are costameres?

Answer 51

Dystrophin complexes forms rib-like lattices on cytoplasmic face of sarcolemma Dissipates force externally

Question 52

What is the current gold standard of treatment for Duchenne muscular dystrophy?

Answer 52

Corticosteroids

Question 53

What do corticosteroids do in the treatment of Duchenne muscular dystrophy?

Answer 53

Maintain/decrease muscle fibre size Counter effects of chronic inflammation Preserve existing muscle fibres Small increase in muscle strength > delays need for wheelchairs