In vivo and in vitro evidence that intrinsic upper- and lower-limb skeletal muscle function is unaffected by ageing and disuse in oldest-old humans

Abstract

Aim: To parse out the impact of advanced ageing and disuse on skeletal muscle function, we utilized both in vivo and in vitro techniques to comprehensively assess upper- and lower-limb muscle contractile properties in 8 young (YG; 25 ± 6 years) and 8 oldest-old mobile (OM; 87 ± 5 years) and 8 immobile (OI; 88 ± 4 years) women.

Methods: In vivo, maximal voluntary contraction (MVC), electrically evoked resting twitch force (RT), and physiological cross-sectional area (PCSA) of the quadriceps and elbow flexors were assessed. Muscle biopsies of the vastus lateralis and biceps brachii facilitated the in vitro assessment of single fibre-specific tension (Po).

Results: In vivo, compared to the young, both the OM and OI exhibited a more pronounced loss of MVC in the lower limb [OM (-60%) and OI (-75%)] than the upper limb (OM = -51%; OI = -47%). Taking into account the reduction in muscle PCSA (OM = -10%; OI = -18%), only evident in the lower limb, by calculating voluntary muscle-specific force, the lower limb of the OI (-40%) was more compromised than the OM (-13%). However, in vivo, RT in both upper and lower limbs (approx. 9.8 N m cm(-2) ) and Po (approx. 123 mN mm(-2) ), assessed in vitro, implies preserved intrinsic contractile function in all muscles of the oldest-old and were well correlated (r = 0.81).

Conclusion: These findings suggest that in the oldest-old, neither advanced ageing nor disuse, per se, impacts intrinsic skeletal muscle function, as assessed in vitro. However, in vivo, muscle function is attenuated by age and exacerbated by disuse, implicating factors other than skeletal muscle, such as neuromuscular control, in this diminution of function.

Keywords: in vitro; in vivo; oldest-old; sarcopenia.

Figure 1. Muscle mass and maximal voluntary contraction characteristics

Panel A: 3 mid-thigh and 3 mid-arm magnetic resonance images (MRI) of representative YG, OM and OI subjects. Panels B–I document maximal voluntary contraction (MVC), muscle volume of quadriceps (Q) and elbow flexors (EF) calculated from the MRI, physiological cross sectional areas (PCSA), and maximal voluntary specific force, respectively, of healthy young (YG), mobile oldest-old (OM), and immobile oldest-old (OI). Data in Panels B–I are presented as mean ± S.E.; * Significantly different from young subjects; † significantly different from OM subjects. ‡ significant within-group difference between Q and EF.

Figure 2. Neuromuscular activation and resting twitch (RT) characteristics

Panel A: Illustrates the in vivo experimental setup. Panel B presents example tracings of the superimposed twitch technique utilized to determine muscle voluntary activation in legs (quadriceps, Q) and arms (elbow flexors, EF). The superimposed twitches (arrows) were imposed at the highest volitional steady-state torque. Representative examples of RT torque-time curves from Q and EF are illustrated in Panel C. Panels D–I document muscle activation, as determined by the superimposed twitch technique, RT peak torque, and RT specific force, respectively, in healthy young (YG), mobile oldest-old (OM), and immobile oldest-old (OI). Data in Panels D–I are presented as mean ± S.E.; * Significantly different from young subjects; † significantly different from OM subjects. ‡ significant within-group difference between EF and Q.

Figure 3. Myosin isoform distribution in leg and arm muscle of healthy young (YG), mobile oldest-old (OM), and immobile oldest-old (OI)

* Significantly different from young subjects.

Figure 4. Cross sectional area (CSA) distribution in fibres from arm and leg muscle of mobile oldest-old (OM), and immobile oldest-old (OI)

Figure 5. Cross sectional area (CSA) and single fibre mechanics

Panels A, B, and C illustrate CSA, maximal isometric force (Fo), and specific tension (Po=Fo/CSA), respectively, of single fibres from the legs (quadriceps, Q) and arms (elbow flexors, EF) of healthy young (YG), mobile oldest-old (OM), and immobile oldest-old (OI). Data are presented as mean ± S.E.; ‡ Significant within-group difference between EF and Q.

Figure 6. The relationship between intrinsic muscle function measured in vitro, single fibre specific tension (Po), and in vivo, resting twitch (RT) specific force

Each point represents the average in vitro and in vivo value obtained from either the leg or arm muscle of a subject (n=5 healthy young (YG), n=3 mobile oldest-old (OM), and n=3 immobile oldest-old (OI).