The chronic leukocyte and inflammatory cytokine responses of older adults to resistance training in normobaric hypoxia; a randomized controlled trial.

TRIAL DESIGN: Older adults experience chronic dysregulation of leukocytes and inflammatory cytokines, both at rest and in response to resistance training. Systemic hypoxia modulates leukocytes and cytokines, therefore this study characterized the effects of normobaric hypoxia on the leukocyte and cytokine responses of older adults to resistance training. METHODS: 20 adults aged 60-70 years performed eight weeks of moderate-intensity resistance training in either normoxia or normobaric hypoxia (14.4% O2), consisting of two lower body and two upper body exercises. Venous blood was drawn before and after the training intervention and flow cytometry was used to quantify resting neutrophils, lymphocytes, monocytes, eosinophils and basophils, in addition to the subsets of lymphocytes (T, B and natural killer (NK) cells). Inflammatory cytokines were also quantified; interleukin 1 beta (IL-1ß), IL-4, IL-6, IL-8, IL-10 and tumor necrosis factor alpha (TNF-α). Acute changes in leukocytes and cytokines were also measured in the 24 h following the last training session. RESULTS: After the intervention there was a greater concentration of resting white blood cells (p = 0.03; 20.3% higher) T cells (p = 0.008; 25.4% higher), B cells (p = 0.004; 32.6% higher), NK cells (p = 0.012; 43.9% higher) and eosinophils (p = 0.025; 30.8% higher) in hypoxia compared to normoxia, though the cytokines were unchanged. No acute effect of hypoxia was detected in the 24 h following the last training session for any leukocyte population or inflammatory cytokine (p < 0.05). CONCLUSIONS: Hypoxic training caused higher concentrations of resting lymphocytes and eosinophils, when compared to normoxic training. Hypoxia may have an additional beneficial effect on the immunological status of older adults. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR). TRIAL NUMBER: ACTRN12623001046695. Registered 27/9/2023. Retrospectively registered. All protocols adhere to the COSORT guidelines.

The acute leukocyte and cytokine response of older adults to resistance exercise in normobaric hypoxia.

Ageing causes a decline in leukocyte function and blunted leukocyte responses to resistance exercise. Systemic hypoxia exposure augments the leukocyte response to resistance exercise in young adults, yet this response remains uncharacterised in older adults. This study characterised the effects of normobaric hypoxia on the acute leukocyte and inflammatory cytokine responses to resistance exercise in older adults. We recruited 20 adults aged 60-70 years to perform an acute bout of resistance exercise in normobaric hypoxia (FiO2 14.4%; n = 10) or normoxia (FiO2 20.93%; n = 10). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% of their predicted 1-repetition maximum. Venous blood was sampled before and up to 24 hours post-exercise to quantify neutrophils, lymphocytes, monocytes, eosinophils, basophils and cytokines (IL-1ß, IL-4, IL-6, IL-8, IL-10, TNFα). Flow cytometry was used to classify lymphocytes as T (CD4+ helper and CD8+ cytotoxic), B and NK cells, in addition to the expression of the senescence marker CD45RA on T cells. The hypoxic group showed a larger lymphocyte response over the 24 hours post-exercise compared to the normoxic group (p = 0.035). Specifically, there were greater concentrations of CD4+ T helper cells following hypoxic exercise compared to normoxia (p = 0.046). There was also a greater proportion of CD45RA+ CD4+ T helper cells, suggesting that the cells were more senescent (p = 0.044). Hypoxia did not impact any other leukocyte population or cytokine following exercise. Normobaric hypoxia increases the lymphocyte response to an acute bout of resistance exercise in older adults.

The effects of normobaric hypoxia on the leukocyte responses to resistance exercise.

There is growing interest in the use of systemic hypoxia to improve the training adaptations to resistance exercise. Hypoxia is a well-known stimulator of the immune system, yet the leukocyte responses to this training modality remain uncharacterised. The current study characterised the acute leukocyte responses to resistance exercise in normobaric hypoxia. The single-blinded, randomised trial recruited 13 healthy males aged 18-35 years to perform a bout of resistance exercise in normobaric hypoxia (14.4% O2; n = 7) or normoxia (20.9% O2; n = 6). Participants completed 4 × 10 repetitions of lower and upper body exercises at 70% 1-repetition maximum. Oxygen saturation, rating of perceived exertion and heart rate were measured during the session. Venous blood was sampled before and up to 24 hours post-exercise to quantify blood lactate, glucose and leukocytes including neutrophils, lymphocytes, monocytes, eosinophils and basophils. Neutrophils were higher at 120 and 180 minutes post-exercise in hypoxia compared to normoxia (p<0.01), however lymphocytes, monocytes, eosinophils and basophils were unaffected by hypoxia. Oxygen saturation was significantly lower during the four exercises in hypoxia compared to normoxia (p < 0.001). However, there were no differences in blood lactate, heart rate, perceived exertion or blood glucose between groups. Hypoxia amplified neutrophils following resistance exercise, though all other leukocyte subsets were unaffected. Therefore, hypoxia does not appear to detrimentally affect the lymphocyte, monocyte, eosinophil or basophil responses to exercise.

The Effect of Normobaric Hypoxia on Resistance Training Adaptations in Older Adults.

ABSTRACT: Allsopp, GL, Hoffmann, SM, Feros, SA, Pasco, JA, Russell, AP, and Wright, CR. The effect of normobaric hypoxia on resistance training adaptations in older adults. J Strength Cond Res 36(8): 2306-2312, 2022-The effect of normobaric hypoxia on strength, body composition, and cardiovascular fitness was investigated after a resistance training intervention in older adults. A single-blinded, randomized control trial recruited 20 healthy adults aged 60-75 years for an 8-week resistance training intervention in normoxia ( n = 10) or normobaric hypoxia (14.4% O 2 ; n = 10). Subjects performed 2 sessions per week of upper-body and lower-body exercises at 70% of 1 repetition maximum (1RM). Pretraining and post-training, maximal oxygen uptake (V̇O 2 max), muscular endurance (30 maximal knee flexions/extensions), and 5RM were assessed, with 5RM used to calculate 1RM. Subjects underwent whole-body dual-energy x-ray absorptiometry (DXA) at pretraining and post-training for fat and lean mass quantification. Significance was set at p < 0.05. Subjects in both groups substantially improved their calculated 1RM strength for leg extension, pectoral fly, row, and squat (normoxia; 30, 38, 27, and 29%, hypoxia; 43, 50, 28, and 64%, respectively); however, hypoxia did not augment this response. Hypoxia did not enhance V̇O 2 max or muscular endurance responses after the training intervention, with no improvements seen in either group. Fat mass and lean mass remained unchanged in both groups after the intervention. In summary, 8 weeks of resistance training in hypoxia was well tolerated in healthy older adults and increased upper-body and lower-body strength. However, the magnitude of strength and lean muscle improvements in hypoxia was no greater than normoxia; therefore, there is currently no evidence to support the use of hypoxic resistance training in older adults.

A Reduction in Selenoprotein S Amplifies the Inflammatory Profile of Fast-Twitch Skeletal Muscle in the mdx Dystrophic Mouse.

Excessive inflammation is a hallmark of muscle myopathies, including Duchenne muscular dystrophy (DMD). There is interest in characterising novel genes that regulate inflammation due to their potential to modify disease progression. Gene polymorphisms in Selenoprotein S (Seps1) are associated with elevated proinflammatory cytokines, and in vitro SEPS1 is protective against inflammatory stress. Given that SEPS1 is highly expressed in skeletal muscle, we investigated whether the genetic reduction of Seps1 exacerbated inflammation in the mdx mouse. F1 male mdx mice with a heterozygous Seps1 deletion (mdx:Seps1-/+) were generated. The mdx:Seps1-/+ mice had a 50% reduction in SEPS1 protein expression in hindlimb muscles. In the extensor digitorum longus (EDL) muscles, mRNA expression of monocyte chemoattractant protein 1 (Mcp-1) (P = 0.034), macrophage marker F4/80 (P = 0.030), and transforming growth factor-ß1 (Tgf-ß1) (P = 0.056) were increased in mdx:Seps1-/+ mice. This was associated with a reduction in muscle fibre size; however, ex vivo EDL muscle strength and endurance were unaltered. In dystrophic slow twitch soleus muscles, SEPS1 reduction had no effect on the inflammatory profile nor function. In conclusion, the genetic reduction of Seps1 appears to specifically exacerbate the inflammatory profile of fast-twitch muscle fibres, which are typically more vulnerable to degeneration in dystrophy.