Blunted angiogenesis and hypertrophy are associated with increased fatigue resistance and unchanged aerobic capacity in old overloaded mouse muscle

Abstract

We hypothesize that the attenuated hypertrophic response in old mouse muscle is (1) partly due to a reduced capillarization and angiogenesis, which is (2) accompanied by a reduced oxidative capacity and fatigue resistance in old control and overloaded muscles, that (3) can be rescued by the antioxidant resveratrol. To investigate this, the hypertrophic response, capillarization, oxidative capacity, and fatigue resistance of m. plantaris were compared in 9- and 25-month-old non-treated and 25-month-old resveratrol-treated mice. Overload increased the local capillary-to-fiber ratio less in old (15 %) than in adult (59 %) muscle (P < 0.05). Although muscles of old mice had a higher succinate dehydrogenase (SDH) activity (P < 0.05) and a slower fiber type profile (P < 0.05), the isometric fatigue resistance was similar in 9- and 25-month-old mice. In both age groups, the fatigue resistance was increased to the same extent after overload (P < 0.01), without a significant change in SDH activity, but an increased capillary density (P < 0.05). Attenuated angiogenesis during overload may contribute to the attenuated hypertrophic response in old age. Neither was rescued by resveratrol supplementation. Changes in fatigue resistance with overload and aging were dissociated from changes in SDH activity, but paralleled those in capillarization. This suggests that capillarization plays a more important role in fatigue resistance than oxidative capacity.

Impaired skeletal muscle performance as a consequence of random functional capillary rarefaction can be restored with overload‐dependent angiogenesis

“…1998; Deveci & Egginton, 2002; Ballak et al . 2016), with enhanced resistance to fatigue after overload (Fig. 3, Table 1), regardless of microvascular impediment.…”

“…2011; Ballak et al . 2016) was affected by an underlying constrained microcirculation in otherwise healthy tissue. Compensatory overload after synergist extirpation occurs due to the additional functional demands imposed on remaining muscles.…”

“…1998; Deveci & Egginton, 2002) coupled with increased fatigue resistance (Frischknecht & Vrbova, 1991; Ballak et al . 2016) due to angiogenic remodelling (Egginton et al . 1998, 2011; Williams et al .…”

Reduced dietary intake of micronutrients with antioxidant properties negatively impacts muscle health in aged mice

“…Several of these micronutrients contribute to the antioxidant capacity, which is impaired during ageing . The increased production of reactive oxygen species with age that exceeds the antioxidant defence capacity may contribute to lower physical function and a reduced potential to adapt to muscle exercise and mechanical loading . An age‐related reduction in muscle mitochondrial DNA and an increased mtDNA oxidation could play a role in this phenomenon .…”

Methodological issues limit interpretation of negative effects of satellite cell depletion on adult muscle hypertrophy

“…A very small increase or even reduction in crosssectional area (CSA) accompanied by an increase in the number of fibers has previously been reported in a few studies (Ferry et al, 2014;Joanne et al, 2012;Parsons et al, 2004), but to our knowledge not for observation periods as short as 2 weeks, and even most long-term studies report a robust hypertrophy (Ballak et al, 2016(Ballak et al, , 2015Dunn et al, 1999Dunn et al, , 2000Guerci et al, 2012;Ito et al, 2013;Johnson and Klueber, 1991;White et al, 2009). Although fiber splitting was not studied in either of the two papers, and is not a well-understood phenomenon, we agree that it is a reasonable speculation about the causes of the poor hypertrophy observed in the SC+OL+ muscles by (since we observed more robust hypertrophy, we think it less likely to be a significant issue in our own work).…”