Blood flow restriction exercise stimulates mTORC1 signaling and muscle protein synthesis in older men

Abstract

The loss of skeletal muscle mass during aging, sarcopenia, increases the risk for falls and dependence. Resistance exercise (RE) is an effective rehabilitation technique that can improve muscle mass and strength; however, older individuals are resistant to the stimulation of muscle protein synthesis (MPS) with traditional high-intensity RE. Recently, a novel rehabilitation exercise method, low-intensity RE, combined with blood flow restriction (BFR), has been shown to stimulate mammalian target of rapamycin complex 1 (mTORC1) signaling and MPS in young men. We hypothesized that low-intensity RE with BFR would be able to activate mTORC1 signaling and stimulate MPS in older men. We measured MPS and mTORC1-associated signaling proteins in seven older men (age 70+/-2 yr) before and after exercise. Subjects were studied identically on two occasions: during BFR exercise [bilateral leg extension exercise at 20% of 1-repetition maximum (1-RM) with pressure cuff placed proximally on both thighs and inflated at 200 mmHg] and during exercise without the pressure cuff (Ctrl). MPS and phosphorylation of signaling proteins were determined on successive muscle biopsies by stable isotopic techniques and immunoblotting, respectively. MPS increased 56% from baseline after BFR exercise (P<0.05), while no change was observed in the Ctrl group (P>0.05). Downstream of mTORC1, ribosomal S6 kinase 1 (S6K1) phosphorylation and ribosomal protein S6 (rpS6) phosphorylation increased only in the BFR group after exercise (P<0.05). We conclude that low-intensity RE in combination with BFR enhances mTORC1 signaling and MPS in older men. BFR exercise is a novel intervention that may enhance muscle rehabilitation to counteract sarcopenia.

Hypoxia and Resistance Exercise: A Comparison of Localized and Systemic Methods

“…Etheridge et al [126] reported that following moderate-intensity IHRT (6 sets of 8 repetitions at 70% 1RM; 3.5 h exposure to F I O 2 = 0.12), MPS was blunted, despite an increase in S6K1 phosphorylation. These results are somewhat disparate with BFR research, where increases in S6K1 phosphorylation have been reported in congruence with increases in MPS [51,77]. While speculative, Etheridge et al [126] propose that other currently unknown signalling processes might override mTOR signalling in hypoxia, affecting the physiological responses to resistance exercise in hypoxia [126].…”

“…More recently, Fry et al [77] reported increases in both MPS and S6K1 phosphorylation 3 hours after 4 sets of low-intensity (20% 1RM) bilateral knee extensions with BFR, despite no change following equivalent trials without BFR.…”

“…Increased pressure against the cytoskeleton or cellular membrane caused by swelling may be perceived to threaten cellular integrity, causing the cell to initiate a signalling response to reinforce its ultrastructure [46,54,101]. It is suggested that this transient increase in muscle cell volume could activate anabolic signalling cascades, such as mTOR and mitogen-activated protein kinase (MAPK) pathways [12,46,54], which are known to be stimulated by low-intensity resistance exercise with BFR [51,77].…”

Exercise with Blood Flow Restriction: An Updated Evidence-Based Approach for Enhanced Muscular Development

“…The muscular benefits arising from BFR training are often promoted for cohorts where high mechanical loads may be contraindicated or not possible, including postoperation rehabilitation patients [2,3] and the elderly [9,10]. While the vast majority of BFR research has been conducted using untrained participants, several investigations have also demonstrated muscular benefits from BFR in athletic populations [5,[11][12][13][14][15][16][17].…”

“…Importantly, this accumulation of metabolites may increase muscle cell swelling [25], intramuscular anabolic/anti-catabolic signalling [9,26,27], and muscle fibre recruitment [4,28], which are all thought to be beneficial for muscular adaptation [23]. Furthermore, evidence suggests that the hypoxic environment created during BFR may increase the activation and proliferation of myogenic stem cells, enhancing the hypertrophic response [29].…”