Skeletal Muscle Function & in Ageing Flashcards
What are the 3 basic motor unit types?
fast-fatiguable (FG, IIX), fast-resistant (FOG, IIA), slow (SO, I)
Type I muscle fibres
slow oxidative; slow-twitch, small force, high resistance to fatigue
Type IIA muscle fibres
fast oxidative/glycolytic; fast-twitch, medium force, high resistance to fatigue
Type IIX muscle fibres
fast glycolytic; fast-twitch, large force, low resistance to fatigue
Fast muscle fibres are ______ in size and fatigue _______
larger, more easily
Slower muscle fibres are _______ in size and are fatigue ________
smaller, resistant
What are ‘pure’ muscle fibres?
have one type of MyHC ie either fast or slow
What are ‘hybrid’ muscle fibres?
contain multiple forms of MyHC ie combinations of fast and slow
T/F Muscles are static units
False; muscle fibres are highly malleable and change their properties based on thes timulus they receive
T/F Within our muscles there is either only pure fibres or hybrid fibres
False; there is a combination of pure and hybrid
T/F Slow contracting muscle (eg soleus) do not contain any fast-twitch (IIA or IIX) fibres
False; they contain relatively smaller amounts but they are still present
What is the role of myostatin?
Negative regulator of muscle mass; if it is inhibited it results in muscle hypertrophy
What is the role of myostatin in muscle wasting?
In muscle wasting disorders eg inflammatory environments, myostatin levels rise contributing to atrophy of muscle
What is spinal muscular atrophy (SMA)?
Loss of motor neurons and dendritic contracts to muscle results in atrophy and loss of function
T/F Cachexic weight loss can directly cause death
True; >20% of cancer-related deaths are attributable to cachexia as loss of muscle mass over 40% is fatal
T/F Cachexia impairs patient respons to chemo and radiotherapies
True
T/F Muscle is an endocrine organ
True; it produces and releases different hormones into the circulation
In cachexia and critical illness myopathy, muscle
atrophies and has disrupted architecture
What is critical illness myopathy?
An inflammatory environment associated with infection sets of a cascade of signalling pathways leading to degradation of muscle protein and atrophy over a matter of days
T/F Muscle fibres cannot switch types
False; eg stimulation of a fast twitch muscle like TA with low-freqeuency slow-twitch type innervation can change it from FF to SO
What is sarcopenia?
Age-related muscle wasting with associated loss of muscle function
What changes in ageing are associated with sarcopenia?
disuse, changing endocrine function, chronic diseases, inflammation, insulin resistance, nutritional deficiencies or dietary changes
T/F Cachexia is the same as sarcopenia
False; cachexia may be a component of sarcopenia, but sarcopenia is specifically age-related
Diagnosis of sarcopenia should be considered in
older patients with observed declines in physical function, strength, or overall health
Initial criteria for sarcopenia diagnosis are
bedridden, cannot independently rise from chair, gait speed less than 1m/s
What changes accompany loss of muscle mass in ageing?
Increase in non-contractile material - connective tissue and fat; change in architecture of the muscle
Which type of physical activity, running or weightlifting/explosive force events declines faster in ageing?
Weight lifting/quick contraction activities that are dynamic and require a lot of muscle power decline at an even greater rate
What is muscle weakness?
Inability to develop initial force appropriate for the circumstances eg unable to rise from a chair
Muscle strength declines steeply beyond age
50
T/F Slow muscles are more susceptible to age related changes
False; fast muscles
What are the mechanisms of age-related motor unit remodelling?
loss of fast type II motor unit innervation results in death of fast-twitch muscle fibres; expansion of type I motor units innervates fast fibres and converts them to slow fibres
What is intrinsic weakness?
With ageing, force produced per CSA of muscle fibre is decreased
What is fibre-type grouping?
selective loss of fast motor units leads to loss of checkerboard pattern of fast and slow fibre distribution
Fibre-type grouping is seen in
neuromuscular disorders AND sarcopenia
What is the cause of the slowing of contraction and relaxation of muscle with age?
impaired release and reuptake of Ca2+ by the SR
T/F Age-related changes in speed of contraction occur concurrently with atrophy
False; these changes occur well before there is significant loss of muscle mass
What happens to motor neurons with ageing?
MNs are lost, numbers and diameters of motor axons decrease; some fibres die, others survive due to sprouting from slow fibres
What changes occur at the NMJ with age?
widening of the end-plate, longer nerve terminals, fewer side branches - futile remodelling
What changes occur to nerves in ageing?
Increase in connective tissue between axons, aberrant small diameter axons, dysmyelination
What is responsible for the stiffening of muscles with age?
Muscles lose their elasticity because connective tissue increases between muscle fibres
Strength training in the elderly increases what type of fibres?
type II (fast)
What contributes to the inability to combat sarcopenia even with optimal strength training?
Decreased circulating levels of anabolic hormones - GH, IGF-1, testosterone - compromises efficiency of muscle regeneration or repair of daily wear and tear
What characterized DMD?
Generalized weakness and muscle wasting affecting limb and trunk muscles first; calves are often enlarged; elevated CK levels
What is Gower’s sign?
due to weakness of limb muscles, need to walk self off of floor up the thighs to stand, can’t just stand using limb muscles
What changes occur to the appearance of muscle in DMD?
loss of fibres, variable size of remaining fibres, significant fibrotic infiltration (fat and CT)
DMD is caused by
multiple mutations on dystrophin gene (X-linked) causing deficiency in dystrophin expression, a ctyoskeletal protein
What is the normal role of dystrophin?
Ctyoskeletal protein involved in shock absorption and force transmission by anchoring actin to transmembrane proteins, anabolic signalling blood flow signalling via connection to laminin
What is the difference in dystrophin in Becker MD?
there are significant amounts of abnormal, smaller stable fragments that confer some stability to muscles
Dystrophin is postulated to have a structural role in stabilizing the ________ during contraction via the ________
sarcolemma; dystrophin-glycoprotein complex (DGC)
What are costameres?
Lattices of DGC on the cytoplasmic face of the sarcolemma that join sarcomeres to laminin in the EXM`
What is the result of loss of costameres in DMD?
Membrane fragility and disruption causing instability in the muscle fibres - membranes tear on activation leading to fibrosis of ECM and leakage of calcium ions which can activate muscle destruction (proteases, phospholipases)
What is the role of BPG-15 in DMD?
Increases HSP-72 (HSPs help fold misfolded proteins) to improve SERCA levels (takes up Ca into SR) to improve muscle function
