M8 Muscle wasting conditions: a shift in the balance Flashcards
1
Q
Sarcopenia
A
- loss of muscle mass, strength and function associated with age
- Protein BD > Syn
- Most notable in the lower limb muscles
- Type II specific loss/necrosis
2
Q
Mechanism of sarcopenia
A
- Multifactorial and complex
- ↓nutrients → ↓protein syn
- Changes in hormone levels (menopause)
- Neuronal changes/loss of motor units → muscle fibre death
- ↓ activity
- ↑Anti-growth factors and low grade inflammation
- Loss of satellite cell function
3
Q
Basal rate of protein synthesis in young and eldery
A
- However, there is no difference between basal protein synthesis in fasted state of young and elderly
4
Q
Why is there then a difference between protein synthesis of the young and elderly?
A
- ↓Protein synthetic response to meats and exercise
5
Q
Inflammation in muscle wasting disorders
A
- Inflammation leads to anabolic resistance → impaired muscle regeneration
- Extent → determines rate of muscle wasting
- Triggers muscle BD pathways → ↓protein synthesis
6
Q
Muscle wasting in ICU
A
- Muscle wasting severe in ICU due to inactivity and ↓food intake (rapid and severe)
- ↑severity of illness → ↑muscle wasting
- ↓in physical and mental capacity → does not resore back to normal levels
7
Q
Where are muscle samples usually taken from
A
- Measures taken by looking at the CSA of rectus femoris
8
Q
Exercise interventions in the ICU
A
- Passively moving legs (cycling) → attenuates muscles loss
9
Q
Effect of LPS administration in mice?
A
- Rapid ↑ in inflammatory signalling after lipopolysaccharide admin in mice
- Acute and prolonged (onset in 4-6h)
- Animals stop eating after injection of LPS → ↓muscle protein synthesis
- ↓muscle mass by 25% in 24hrs
- LPS → stimulates glucose uptake in tissues → ↓circulating glucose
10
Q
Mechanism of LPS administration in mice
A
- Binds to TLR4 → recruit NFkB to nuclues → produce inflammatory cytokines
11
Q
What is achieved from administering LPS?
A
- Used to study metabolism of inflammation
12
Q
Cancer cachexia
A
- ↓food intake and ↓muscle mass
- Altered protein AA/carb/fat metabolism
- Loss of skeletal mass and function
13
Q
What happens as a result of increased muscle BD?
A
- ↑ AA release (i.e alanine/glutamine)
- Glutamine converted into serine → ↑growth of cells/tumours
- ↓IGF1, ↑myostatin
- Stimulates FOXO and E3 ligases (atrogin/MURF)
14
Q
Atrogin/MURF-1
A
- Poly-ubiquinated proteins are recognised by proteasome and broken down
- ↓capacity of protein synthetic machinery and induces muscle wasting
15
Q
Atrogin-1
A
- Atrogin-1 → indirectly ↓capacity of protein synthetic machinery
