Le fibre muscolari: modificazioni con lo sviluppo, invecchiamento e allenamento

Marsilio Saccavini
UOC Degenza di Medicina Riabilitativa TREVISO

Developmental MHC and slow MHC isoforms
‡ Human genome contains at least 10 genes for MHC but only 7 so far identified in mature fibres (more actually expressed?). ‡ Two isoforms predominate during development: MHCemb & MHCneo ‡ In some muscles two additional slow MHC found: a tonic and an alpha cardiac (MHCIton & MHCEcard)
± MHCIton present in mature extrafusal extraocular muscles & developing intrafusal fibres ± MHCcard found in extrafusal fibres of mature extraocular and masticary muscles and in intrafusal fibres.

‡ Spindle-specific MHC found in intrafusal fibres (MHCif)

Development (myogenesis)
‡ Mammalian muscles form by the fusion of myoblasts into myotubes: i) primary myotubes and ii) secondary myotubes
± PRIMARY MYOTUBES: appear between 8-10 wks of gestation (i.e. prior motor innervation), contain: slow MHC, MHCemb, MHCneo ± SECONDARY MYOTUBES: formed around 10-18 wks of gestation, contain: fast MHC, MHCemb, MHCneo

Myogenesis (cont)
± By 18-20 wks gestation most of fibres from the PRIMARY MYOTUBES recognizable as large dia. type I fibres (slow MHC) ± By 15-18 wks gestation most fibres from SECONDARY MYOTUBES initially express fast MHC, MHCemb, MHCneo. With maturation, MHCemb & MHCneo disappear and fast MHC exclusively expressed ± In the secondary fibres, the ultimate expression of fast or slow MHCs seems determined by extrinsic factors e.g. innervation increases expression of slow MHC in human muscle ± Normal size type I fibre appear at ~30 wks gestation ± Type IIA & IIB fibres are distinguishable at ~32-36 wks gestation

Order of MHC expressions

MHCemb pMHCneo p MHCslow/MHCfast

‡ An increase in the proportion of fibres coexpressing MHCI and -IIa and MHC-IIa and -IIb has been found in the vastus lateralis m. of old subjects (~70 yr-old). Similar findings for the biceps (Klitgaard et. al 1989). ‡ In the very old (80+ years) ~ 50% of all fibers examined coexpresses two or three MHC isoforms (Andersen et al.1999). ‡ Therefore ageing leads to an increased coexpression of different MHC isoforms. (ongoing fibre equilibrium?) ‡ These differences, however, are region specific.

Fibre transformations with strength training in young and old adults

Fibre type transformations
‡ Adaptations to usage Animals
± Buller (1960): µfast p slow¶ muscle transformation by cross-innervation experiments ± Salmons & Vrbová (1969) a µfast p slow¶ transformation brought by low freq. (10Hz) stimulation

MHC expression has evolved according to the functional demand on the muscle (e.g. triceps brachii, vastus lateralis and soleus)

MHC-II composition and contractile properties in arm, thigh and leg muscles

Training-induced fibre transformations

FT and ST fibre hypertrophy

Summary of transformations
Increased use
‡ Type IIB (FG) fibres seem to be lost both a result of sprint as well as endurance training ‡ MHC-IIB is probably the µdefault gene¶ which tranforms into MHC-IIA (FOG) following increased usage ‡ Sprint training results also in a decrease in MHCIIB but also of MHC-I, thus two paths for MHCIIA expression may exist:


Transformations (cont.)
Decreased use
Spinal cord injury patients display a reduction of MHC-I isoforms and an increase in MHC-IIB. A reduction in proportion of type I fibres observed after cast immobilisation Confounding evidence after bed rest. Therefore SOME evidence for slow p fast transformation exists, though issue not resolved