Sarcopenia Flashcards
what is sarcopenia?
loss of skeletal muscle mass and strength that occurs with advancing age
from what age do we start to see a decrease in skeletal muscle mass?
25 years
how would the skeletal muscle mass of a 25 year old compare to a 65 year old?
more fat tissue
loss of muscle mass
increase in intramuscular adipose
reduced strength due to muscle power decline
effect on metabolism
how is sarcopenia diagnosed?
- skeletal muscle mass decline
using the measurement of CSA of midthigh- MRI
- CT scan
- function and strength decline
- grip strength
- gait speed
why do we see a muscle quality decline with ageing?
older muscle containing fewer and less efficient mitochondria
what is the function of skeletal muscle?
strength
posture
movement
metabolism/metabolic rate
what is the loss of muscle mass/ sarcopenia described as?
reduced strength
loss of physical function and independence
increase risk of falls and gait balance problems
prolonged hospitalisation and recover time
reduced withstanding chemotherapy treatments for cancer
how does skeletal muscle mass regulate metabolism/metabolic rate?
skeletal muscle is the major organ for insulin-stimulated blood glucose uptake
how does obesity inhibit insulin-simulated glucose uptake?
by increasing intracellular fat accumulation
what does obesity cause within the skeletal muscle?
accumulation of triglycerides
= inhibition of glucose stimulation
= decrease [GLUT4]
= type 2 diabetes
what are increasing risk factors on developing type 2 diabetes?
obesity
high BMI
high central adiposity distribution (waist-to-hip ratio (WHR)) HIGH WHR
describe WHR results?
> 0.8 HIGH WHR (apple shaped) = metabolic disorders
<0.8 LOW WHR (pear shaped)
what are the different types of muscle fibres?
what are slow twitch muscle characterised by?
mostly Type 1 slow-twitch fibres
oxidative metabolism
fatigue resistant
postural muscle contains mostly slow type 1 fibres
MARATHON RUNNERS HAVE MUSCLE W HIGH % OF SLOW TWITCH FIBRES
what are fast twitch muscle characterised by?
mostly Type 2 fast fibres (IIA and IIB)
fatigue quickly
SPRINTERS HAVE MUSCLE W HIGH % OF FAST TWITCH FIBRES
what happens within the skeletal muscle with patients with osteoarthritis?
type 2 fast fibre atrophy
type 2 (fast) fibres are smaller in size in OA pt muscles compared to healthy pts
what happens within the skeletal muscle with patients with chronic obstructive pulmonary disease (COPD)?
increase % of type IIX (fast) fibres
reduced size of Type IIX fibres
what does atrophy of type 2 fibres cause?
less precise control
loss of balance
loss of speed
reduced maximal force generation
what is required homeostasis of skeletal muscle mass?
protein turnover
1-2% per day
300-600g muscle protein
how is protein turnover maintained in skeletal muscle mass?
- skeletal muscle protein synthesis
- activity of muscle anabolic signalling pathways - skeletal muscle protein degradation
- activity of muscle catabolic signalling pathways
what is the catabolic signalling pathways in skeletal muscle?
what is the importance of muscle specific E3 ligases ?
regulates atrophic signalling in catabolic signalling pathways in protein degradation
what are the signals produced by muscle specific E3 ligases
what does atrophy and hypertrophy mean?
hypertrophy (increase exercise)
atrophy (ill/ decrease movement)
how does ill/decrease movement have an impact on people ?
ill/decreased movement = atrophy signalling = increase protein degradation = increase muscle ageing
what does atrophy and hypertrophy mean in anabolic signalling
atrophy (ill/ decrease movement) = protein degradation
hypertrophy (increase exercise) = protein synthesis
what is the myostatin pathway?
negative regulator of muscle mass
binds to active receptor Type IIB (ActRIIB receptor)
= activates FOXO = induction of Muscle mass E3 ligases = increase atrophy = protein degradation
what happens if you inhibit the myostatin pathway?
produces muscle hypertrophy = protein synthesis = increase muscle mass
what other factors drive muscle ageing?
decreased physical activity or immobulisation/disuse
anabolic blunting
increased inflammatory cytokines (inflammaging)
nutrition/ protein deficiency
neuromuscular changes
testosterone and growth hormone decline
what is anabolic blunting in elderly?
increase age = decrease in anabolic stimulation
what pro-inflammatory cytokines drive muscle ageing?
increase TNF-alpha, IL-1B, IL-6
promote atrophy of myotubes
TNF-alpha induces muscle E3 ligases = inducing atrophy
what are therapeutics used to modulate muscle ageing?
no approved
what are therapeutics in development to modulate muscle ageing?
Myostatin monoclonal antibodies
* Efficacious in murine models (increased muscle mass and strength)
* Humanised antibody has shown tolerability in Phase I (Myo-029)
A soluble myostatin decoy receptor (ActRIIB-Fc) is an alternative strategy
