Sarcopenia

Question 1

what is sarcopenia?

Answer 1

loss of skeletal muscle mass and strength that occurs with advancing age

Question 2

from what age do we start to see a decrease in skeletal muscle mass?

Answer 2

25 years

Question 3

how would the skeletal muscle mass of a 25 year old compare to a 65 year old?

Answer 3

more fat tissue
loss of muscle mass
increase in intramuscular adipose
reduced strength due to muscle power decline
effect on metabolism

Question 3

how is sarcopenia diagnosed?

Answer 3

1. skeletal muscle mass decline
   using the measurement of CSA of midthigh
   
   • MRI
   • CT scan
2. function and strength decline
   
   • grip strength
   • gait speed

Question 4

why do we see a muscle quality decline with ageing?

Answer 4

older muscle containing fewer and less efficient mitochondria

Question 5

what is the function of skeletal muscle?

Answer 5

strength
posture
movement
metabolism/metabolic rate

Question 6

what is the loss of muscle mass/ sarcopenia described as?

Answer 6

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

Question 7

how does skeletal muscle mass regulate metabolism/metabolic rate?

Answer 7

skeletal muscle is the major organ for insulin-stimulated blood glucose uptake

Question 8

how does obesity inhibit insulin-simulated glucose uptake?

Answer 8

by increasing intracellular fat accumulation

Question 9

what does obesity cause within the skeletal muscle?

Answer 9

accumulation of triglycerides
= inhibition of glucose stimulation
= decrease [GLUT4]
= type 2 diabetes

Question 10

what are increasing risk factors on developing type 2 diabetes?

Answer 10

obesity
high BMI
high central adiposity distribution (waist-to-hip ratio (WHR)) HIGH WHR

Question 11

describe WHR results?

Answer 11

> 0.8 HIGH WHR (apple shaped) = metabolic disorders
<0.8 LOW WHR (pear shaped)

Question 12

what are the different types of muscle fibres?

Answer 12

Question 13

what are slow twitch muscle characterised by?

Answer 13

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

Question 14

what are fast twitch muscle characterised by?

Answer 14

mostly Type 2 fast fibres (IIA and IIB)
fatigue quickly

SPRINTERS HAVE MUSCLE W HIGH % OF FAST TWITCH FIBRES

Question 15

what happens within the skeletal muscle with patients with osteoarthritis?

Answer 15

type 2 fast fibre atrophy

type 2 (fast) fibres are smaller in size in OA pt muscles compared to healthy pts

Question 16

what happens within the skeletal muscle with patients with chronic obstructive pulmonary disease (COPD)?

Answer 16

increase % of type IIX (fast) fibres
reduced size of Type IIX fibres

Question 17

what does atrophy of type 2 fibres cause?

Answer 17

less precise control
loss of balance
loss of speed
reduced maximal force generation

Question 18

what is required homeostasis of skeletal muscle mass?

Answer 18

protein turnover
1-2% per day
300-600g muscle protein

Question 19

how is protein turnover maintained in skeletal muscle mass?

Answer 19

1. skeletal muscle protein synthesis
   - activity of muscle anabolic signalling pathways
2. skeletal muscle protein degradation
   - activity of muscle catabolic signalling pathways

Question 20

what is the catabolic signalling pathways in skeletal muscle?

Answer 20

Question 21

what is the importance of muscle specific E3 ligases ?

Answer 21

regulates atrophic signalling in catabolic signalling pathways in protein degradation

Question 22

what are the signals produced by muscle specific E3 ligases

Answer 22

Question 23

what does atrophy and hypertrophy mean?

Answer 23

hypertrophy (increase exercise)
atrophy (ill/ decrease movement)

Question 24

how does ill/decrease movement have an impact on people ?

Answer 24

ill/decreased movement = atrophy signalling = increase protein degradation = increase muscle ageing

Question 25

what does atrophy and hypertrophy mean in anabolic signalling

Answer 25

atrophy (ill/ decrease movement) = protein degradation
hypertrophy (increase exercise) = protein synthesis

Question 26

what is the myostatin pathway?

Answer 26

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

Question 27

what happens if you inhibit the myostatin pathway?

Answer 27

produces muscle hypertrophy = protein synthesis = increase muscle mass

Question 28

what other factors drive muscle ageing?

Answer 28

decreased physical activity or immobulisation/disuse
anabolic blunting
increased inflammatory cytokines (inflammaging)
nutrition/ protein deficiency
neuromuscular changes
testosterone and growth hormone decline

Question 29

what is anabolic blunting in elderly?

Answer 29

increase age = decrease in anabolic stimulation

Question 30

what pro-inflammatory cytokines drive muscle ageing?

Answer 30

increase TNF-alpha, IL-1B, IL-6

promote atrophy of myotubes

TNF-alpha induces muscle E3 ligases = inducing atrophy

Question 31

what are therapeutics used to modulate muscle ageing?

Answer 31

no approved

Question 32

what are therapeutics in development to modulate muscle ageing?

Answer 32

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