Skeletal muscle ageing and disease

Question 1

What is the mechanism of muscle loss with aging?

Answer 1

• Loss of motorneurons (loss of # and decreased diameter or motor axons) - Sprouting may occur; re-innervation of fast fibre is less successful. - Compensatory changes occurring in motor end plates - gradual changes in both pre and post synaptic components (increased end plate size and longer nerve terminals but fewer branches –> decreased SA –> decreased overall innervation)

Question 2

What occurs first with aging and muscle weakness? Loss of innervation or loss of signal form muscle back to brain?

Answer 2

Don’t know hard to test

Question 3

Can changes be reversed?

Answer 3

No but it can be attenuated by adaptation from doing strength training.

Question 4

What hormonal changes are seen with age?

Answer 4

Decreased GH, IGF-1, Testosterone –> Decreased anabolic hormones –> compromised muscle regeneration. Hormone replacement therapy is unsafe and inappropriate.

Question 5

What is the epidemiology and cause and pathophysiology of DMD?

Answer 5

1/3.5k Newborns

Mutation in dystrophin gene (Xp21); often deleted from frameshift mutation –> premature mRNA translation and synthesis of small unstable fragments –> impaired expression.

X-Linked recessibe. 1 in 3 cases from new mutation

Without dystrophin there is gradual degeneration of SkM and CardiacM. as it connect cytoplasmic myofilaments to TM proteins during muscle contraction especially lengtening

Protein associated with DMD

• Dystrophin associated protein (DAP) or dystrophin glycoprotein complex (DGC).
• Dystrophin (connect F actin to a series of TM protein (sacroglycan/dystroglycan complex) which link externally to laminin.

Question 6

What is the onset of DMD?

Answer 6

Early childhood: 2-6 years

Rarely present during infancy; height and weight normal.

Subsequent growth is slow

Question 7

What are the symptoms of DMD?

Answer 7

• Generalised weakness and muscle wasting affecting limb and trunk muscles first
  
  • Proximal lower girdle weakness
  • Calf pseuo-hypertrophy
  • Cardiac and SM also affected –> Cardiorest failure by 20yo
  • Short stature
  • Development delay, difficulty running or climbing stairs
  • Frequent falls

Clinical features

- Between 3-6 gait becomes lodrotic and wadding

• Enlargement of calf-gluteal, lateral vastus, deltoid, infraspinatus

Question 8

What is the cause and pathophysiology of Becker MD

Answer 8

X-Linked recessive. Reading frame of dystrophin is preserved allowing production of larger more useful portion of dystrophin.