Skeletal Muscle Function & Skeletal Muscle in Ageing and Disease Flashcards
Muscles with which characteristics fatigue more easily?
Larger, faster muscle fibres
Muscles with which characteristics are more fatigue resistant?
Smaller, slower muscle fibres
What are the characteristics of the vast variety of muscle fibres between fast-twitch and slow-twitch fibres?
Intermediate speed
Don’t fatigue as easily
What is muscle fibre malleability?
Muscles adapt to stimuli
What is the makeup of muscle fibres based on their type of myosin?
Either pure = have one type of myosin, or as hybrids containing multiple forms
How is lifespan/healthspan extension possible?
Targeting detrimental effects of ageing, including
- Healthy lifestyle
- Actionable/drug-treatable molecular targets
What does frailty and weakness confer a high risk of?
Mortality
Falls
Institutionalisation
Hospitalisation
What is sarcopenia?
Age-associated loss of skeletal muscle mass and function
What is the rate of loss of muscle mass after the age of 50?
1-2%
What is cachexia?
Generalised wasting of muscle and fat, typically associated with tumours
Are sarcopenia and cachexia the same?
Cachexia may be component of sarcopenia but not same thing
Is sarcopenia affected by health behaviours?
Independent of them, but good ones may slow down rate
In whom should sarcopenia be considered?
Patients who
- Are bedridden
- Can’t independently rise from chair
- Have gait speed <1 m/s
How is sarcopenia diagnosed?
Gait speend of <1 m/s and appendicular lean/fat ratio is less than 2 standard deviations young adult
What is the effect of age on physical performance if you are a marathon runner?
Steady decline after peak at 20-40 years
What is the effect of age on physical performance if you are a weight lifter?
More marked decline than marathon runners
What is muscle weakness?
Inability to develop initial force appropriate for circumstances
When does muscle strength start to decline?
After age 50
Which muscle type shows a greater decline in strength with age?
Fast muscles show greater decline than slow muscles
What is the impact of loss of muscle strength with age?
Impacts progressively on physical capacity and work performance
Eventually impacts on activities often taken for granted
What happens if protein synthesis outweighs protein degradation in muscle?
Hypertrophy
What happens if protein degradation outweighs protein synthesis in muscle?
Atrophy
What is dynapenia?
Age-related loss of muscle strength
What is the association between muscle weakness and mortality?
Higher mortality in older people, to degree much higher than cohort who only has low lean mass
What happens in age-related motor unit remodelling?
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
What happens to the size and strength of muscles with age?
Become smaller
Strength decreases
What happens to movement with age
Become slower and less precise
What injuries do you have and increased risk of with age?
Falls
Fractures
What increases as muscle mass decreases?
Connective tissue
Fat
What molecular change slows muscle contractility with age?
Changes in Ca handling affects speed of contracction
How do mitochondria in muscle change with age?
Reduced number
Loss of enzyme content
What happens in strength training for the elderly?
Increases muscle strength
Increases lean total body mass
Increases muscle fibre area
Increases quality of life because of increased function
If strength training is to be a preventative measure in sarcopenia, when must it be started?
Lifelong commitment > start at younger age
What sorts of exercise can help slow the rate of age-related changes in skeletal muscle?
Strength training
Aerobic exercise
Flexibility
Balance
How do hormones contribute to age-related changes in skeletal muscle?
Decreased circulating levels of anabolic hormones
- Growth hormone
- IGF-I
- Testosterone
Compromises efficiency of muscle regeneration as consequence of daily wear and tear
What is muscular dystrophy?
Diverse group of inherited disorders characterised by progressive skeletal muscle weakness and wasting
What causes Duchenne muscular dystrophy?
Lack of dystrophin
- Complete absence/
- Non-functional protein
What is the inheritance pattern of Duchenne muscular dystrophy?
X-linked recessive
What is the implication on genetic counselling if one in three cases of Duchenne muscular dystrophy are the result of a new mutation?
Even with genetic counselling, a new mutation can manifest
What are the clinical features of Duchenne muscular dystrophy?
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
What is Gowers sign?
Can’t stand unaided
What does the muscle in Duchenne muscular dystrophy look like under the microscope?
Variation in size of muscle fibres
Infiltration by connective tissue and fat
Are all muscles affected in Duchenne muscular dystrophy?
Some spared, like extraocular muscles
What are the molecular changes to the muscle in Duchenne muscular dystrophy?
Small diameter of fibres
Lower mechanical stress per unit surface membrane area
Increased sarcolemmal expression of compensatory proteins
What is the inheritance pattern of Becker muscular dystrophy?
X-linked recessive
What is Becker muscular dystrophy?
Similar to Duchenne, but less severe
Manifests later
Slower time course
What protein is affected in Becker muscular dystrophy?
Dystrophin
What is the difference between dystrophin expression in Duchenne and Becker muscular dystrophy?
Duchenne - virtually no dystrophin
Becker - significant amounts of abnormal, smaller molecules
What is dystrophin associated with in the cytoplasm?
Tightly associated with series of transmembrane proteins
What does dystrophin do in muscle cells?
Transmits force across membrane
Stabilises sarcolemma during muscle contraction, especially lengthening actions
What are costameres?
Dystrophin complexes forms rib-like lattices on cytoplasmic face of sarcolemma
Dissipates force externally
What is the current gold standard of treatment for Duchenne muscular dystrophy?
Corticosteroids
What do corticosteroids do in the treatment of Duchenne muscular dystrophy?
Maintain/decrease muscle fibre size
Counter effects of chronic inflammation
Preserve existing muscle fibres
Small increase in muscle strength > delays need for wheelchairs
