Effects of aging and lifelong aerobic exercise on expression of innate immune components in skeletal muscle of women.

This study examined the effects of aging and lifelong aerobic exercise on innate immune system components in the skeletal muscle of healthy women in the basal state and after an unaccustomed resistance exercise (RE) challenge. We also made exploratory between-sex comparisons with our previous report on men. Three groups of women were studied: young exercisers (YE, n = 10, 25 ± 1 yr, V̇o2max: 44 ± 2 mL/kg/min), lifelong aerobic exercisers with a 48 ± 2 yr training history (LLE, n = 7, 72 ± 2 yr, V̇o2max: 26 ± 2 mL/kg/min), and old healthy nonexercisers (OH, n = 10, 75 ± 1 yr, V̇o2max: 18 ± 1 mL/kg/min). Ten Toll-like receptors (TLRs)1-10, TLR adaptors (Myd88, TRIF), and NF-κB pathway components (IκBα, IKKß) were assessed at the mRNA level in vastus lateralis biopsies before and 4 h after RE [3×10 repetitions, 70% 1-repetition maximum (1RM)]. Basal TLR1-10 expression was minimally influenced by age or LLE in women (TLR9 only; OH > YE, +43%, P < 0.05; OH > LLE, +30%, P < 0.10) and was on average 24% higher in women versus men. Similarly, basal adaptor expression was not influenced (P > 0.05) by age or LLE in women but was on average 26% higher (myeloid differentiation primary response 88, Myd88) and 23% lower [Toll interleukin (IL)-1 receptor-containing adaptor-inducing interferon-γ, TRIF] in women versus men. RE-induced changes in women, independent of the group, in TLR3, TLR4, TLR6 (∼2.1-fold, P < 0.05), Myd88 (∼1.2-fold, P < 0.10), and IκBα (∼0.3-fold, P < 0.05). Although there were some similar RE responses in men (TLR4: 2.1-fold, Myd88: 1.2-fold, IκBα: 0.4-fold), several components responded only in men to RE (TLR1, TLR8, TRIF, and IKKß). Our findings support the sexual dimorphism of immunity, with women having greater basal skeletal muscle TLR expression and differential response to unaccustomed exercise than men.NEW & NOTEWORTHY We recently reported that aging increases basal expression of many Toll-like receptors (TLRs) in men and lifelong aerobic exercise does not prevent this effect. In addition, a resistance exercise (RE) challenge increased the expression of many TLRs. Here we show that basal TLR expression is minimally influenced by aging in women and findings support the sexual dimorphism of immunity, with women having greater basal skeletal muscle TLR expression and a differential response to unaccustomed exercise than men.

NASA SPRINT exercise program efficacy for vastus lateralis and soleus skeletal muscle health during 70 days of simulated microgravity.

The efficacy of the NASA SPRINT exercise countermeasures program for quadriceps (vastus lateralis) and triceps surae (soleus) skeletal muscle health was investigated during 70 days of simulated microgravity. Individuals completed 6° head-down-tilt bedrest (BR, n = 9), bedrest with resistance and aerobic exercise (BRE, n = 9), or bedrest with resistance and aerobic exercise and low-dose testosterone (BRE + T, n = 8). All groups were periodically tested for muscle (n = 9 times) and aerobic (n = 4 times) power during bedrest. In BR, surprisingly, the typical bedrest-induced decrements in vastus lateralis myofiber size and power were either blunted (myosin heavy chain, MHC I) or eliminated (MHC IIa), along with no change (P > 0.05) in %MHC distribution and blunted quadriceps atrophy. In BRE, MHC I (vastus lateralis and soleus) and IIa (vastus lateralis) contractile performance was maintained (P > 0.05) or increased (P < 0.05). Vastus lateralis hybrid fiber percentage was reduced (P < 0.05) and energy metabolism enzymes and capillarization were generally maintained (P > 0.05), while not all of these positive responses were observed in the soleus. Exercise offsets 100% of quadriceps and approximately two-thirds of soleus whole muscle mass loss. Testosterone (BRE + T) did not provide any benefit over exercise alone for either muscle and for some myocellular parameters appeared detrimental. In summary, the periodic testing likely provided a partial exercise countermeasure for the quadriceps in the bedrest group, which is a novel finding given the extremely low exercise dose. The SPRINT exercise program appears to be viable for the quadriceps; however, refinement is needed to completely protect triceps surae myocellular and whole muscle health for astronauts on long-duration spaceflights.NEW & NOTEWORTHY This study provides unique exercise countermeasures development information for astronauts on long-duration spaceflights. The NASA SPRINT program was protective for quadriceps myocellular and whole muscle health, whereas the triceps surae (soleus) was only partially protected as has been shown with other programs. The bedrest control group data may provide beneficial information for overall exercise dose and targeting fast-twitch muscle fibers. Other unique approaches for the triceps surae are needed to supplement existing exercise programs.

Muscle-derived microRNAs correlated with thigh lean mass gains during progressive resistance training in older adults.

Resistance training (RT) remains the most effective treatment for age-related declines in muscle mass. However, many older adults experience attenuated muscle hypertrophy in response to RT when compared with younger adults. This may be attributed to underlying molecular processes that are dysregulated by aging and exacerbated by improperly prescribed RT weekly volume, intensity, and/or frequency doses. MicroRNAs (miRNAs) are key epigenetic regulators that impact signaling pathways and protein expression within cells, are dynamic and responsive to exercise stimuli, and are often dysregulated in diseases. In this study, we used untargeted miRNA-seq to examine miRNA in skeletal muscle and serum-derived exosomes of older adults (n = 18, 11 M/7 F, 66 ± 1 yr) who underwent three times per wk RT for 30 wk [e.g., high intensity three times/wk (HHH, n = 9) or alternating high-low-high (HLH) intensity (n = 9)], after a standardized 4-wk washin. Within each tissue, miRNAs were clustered into modules based on pairwise correlation using weighted gene correlation network analysis (WGCNA). Modules were tested for association with the magnitude of RT-induced thigh lean mass (TLM) change [as measured by dual-energy X-ray absorptiometry (DXA)]. Although no modules were unique to training dose, we identified miRNA modules in skeletal muscle associated with TLM gains irrespective of exercise dose. Using miRNA-target interactions, we analyzed key miRNAs in significant modules for their potential regulatory involvement in biological pathways. Findings point toward potential miRNAs that may be informative biomarkers and could also be evaluated as potential therapeutic targets as an adjuvant to RT to maximize skeletal muscle mass accrual in older adults.NEW & NOTEWORTHY In this work, we identified a set of microRNAs correlated with thigh lean mass gains in a group of older adults. To our knowledge, this is the first time these microRNAs have been identified as novel predictive biomarkers correlating with lean mass gains in aging adults. As biomarkers, these may help interventionalists identify older individuals that are positively responding to an exercise intervention.

Higher resistance training volume offsets muscle hypertrophy nonresponsiveness in older individuals.

The magnitude of muscle hypertrophy in response to resistance training (RT) is highly variable between individuals (response heterogeneity). Manipulations in RT variables may modulate RT-related response heterogeneity; yet, this remains to be determined. Using a within-subject unilateral design, we aimed to investigate the effects of RT volume manipulation on whole muscle hypertrophy [quadriceps muscle cross-sectional area (qCSA)] among nonresponders and responders to a low RT dose (single-set). We also investigated the effects of RT volume manipulation on muscle strength in these responsiveness groups. Eighty-five older individuals [41M/44F, age = 68 ± 4 yr; body mass index (BMI) = 26.4 ± 3.7 kg/m2] had one leg randomly allocated to a single (1)-set and the contralateral leg allocated to four sets of unilateral knee-extension RT at 8-15 repetition maximum (RM) for 10-wk 2 days/wk. Pre- and postintervention, participants underwent magnetic resonance imaging (MRI) and unilateral knee-extension 1-RM strength testing. MRI typical error (2× TE = 3.27%) was used to classify individuals according to responsiveness patterns. n = 51 were classified as nonresponders (≤2× TE) and n = 34 as responders (>2× TE) based on pre- to postintervention change qCSA following the single-set RT protocol. Nonresponders to single-set training showed a dose response, with significant time × set interactions for qCSA and 1-RM strength, indicating greater gains in response to the higher volume prescription (time × set: P < 0.05 for both outcomes). Responders improved qCSA (time: P < 0.001), with a tendency toward higher benefit from the four sets RT protocol (time × set: P = 0.08); on the other hand, 1-RM increased similarly irrespectively of RT volume prescription (time × set: P > 0.05). Our findings support the use of higher RT volume to mitigate nonresponsiveness among older adults.NEW & NOTEWORTHY Using a within-subject unilateral design, we demonstrated that increasing resistance training (RT) volume may be a simple, effective strategy to improve muscle hypertrophy and strength gains among older adults who do not respond to low-volume RT. In addition, it could most likely be used to further improve hypertrophic outcomes in responders.