scholarly journals Loss of Hypoxia Signaling Limits Physiologic and Muscle Adaptations to Aerobic Exercise in Aging

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. 684-685
Author(s):  
Yori Endo ◽  
Mehran Karvar ◽  
Yuteng Zhang ◽  
Shayan Olumi ◽  
Indranil Sinha

Abstract To assess the differential effects of exercise with age, Young (Y, 10-12 weeks) and Old (O, 23-25 months) mice were subjected to regimented treadmill running or no regimented exercise. Y, trained mice experienced a significant increase in maximal distance running, maximal speed of running, and lean muscle mass in comparison to age-matched, untrained controls. O mice did not improve significantly in any of these measures following training. Transcriptome analysis of gastrocnemius from Y mice demonstrated differential regulation of 120 genes with exercise. None of these genes were similarly regulated in the O group. Genes most upregulated following exercise in Y mice were direct targets of the hypoxia signaling pathway. Immunoblotting demonstrated that aryl hydrocarbon receptor nuclear translocator (ARNT), a critical regulator of hypoxia signaling, increased 3-fold with exercise in Y mice, but this increase was absent in O mice following exercise. To assess whether this loss of ARNT in O muscle impaired the exercise response, we generated a mouse with inducible, skeletal muscle-specific knockout of ARNT (ARNT muscle (m) KO). Following regimented exercise, ARNT mKO mice did not improve maximal distance running, maximal running speed, or lean muscle mass in comparison to untrained ARNT mKO mice. Littermate, age-matched ARNT wild type mice increased significantly in all of these measures following training. Administration of ML228, an ARNT agonist, increased maximal running distance and speed in response to exercise training in O mice. These results suggest that restoration of ARNT and hypoxia signaling may restore the physiologic response to exercise in aging.

2020 ◽  
Vol 4 (Supplement_1) ◽  
pp. 489-489
Author(s):  
Yori Endo ◽  
Yuteng Zhang ◽  
Bin Li ◽  
Michael MacArthur ◽  
Indranil Sinha

Abstract Hypoxia signaling is essential for angiogenesis and metabolic regulation during exercise. Our previous study has demonstrated an age-related loss of ARNT resulting in limited muscle regeneration. To explore the role of hypoxia signaling in physiological performance in relation to aging, we generated a mouse model with skeletal muscle-specific knockout of ARNT (ARNT mKO). ARNT mKO and ARNT WT mice were subjected to a sedentary activity or treadmill running exercise regime at an increasing speed of 8-12 m/min for 40 minutes, three times weekly over the course of 8 weeks. ARNT levels was 3-fold lower in old mice compared to young. The exercised WT mice exhibited 52% greater increase over the sedentary group in exercise endurance as measured by the maximum running distance (490.92±154.28 vs 237.76±135.19m, p<0.01). In contrast, ARNT mKO mice did not benefit from exercise (231.85±198.61 vs 167.27±136.56m, p=0.41). The maximum running speed was severely restricted in the trained ARNT mKO mice versus WT (16±1.63 m/min vs 26.67±2.45 m/min, p<0.001). Cross-sectional area of myofibers increased significantly following exercise in WT mice (2270 vs 2960 □m2, p=0,015) indicating muscle hypertrophic response, while no change was observed in the ARNT mKO group (2101 vs 2378□m2, p=0,21). Further, exercise increased femoral artery blood flow by 41% in ARNT WT mice, but not in ARNT mKO mice (898.96±52.33 vs 802.86±48.43, p=0.20). These data suggest that ARNT is essential for physiological response to exercise


Author(s):  
Luke Del Vecchio ◽  
Nattai Borges ◽  
Campbell MacGregor ◽  
Jarrod D. Meerkin ◽  
Mike Climstein

Background: Previous research highlighted positive musculoskeletal adaptations resulting from mechanical forces and loadings distinctive to impacts and movements with sports participation. However, little is known about these adaptations in combat athletes. The aim of this study was to quantify bone mineral density, lean muscle mass and punching and kicking power in amateur male combat athletes. Methods: Thirteen male combat athletes (lightweight and middleweight) volunteered all physiological tests including dual energy X-ray absorptiometry for bone mineral density (BMD) segmental body composition (lean muscle mass, LMM), muscle strength and striking power, sedentary controls (n = 15) were used for selected DXA outcome variables. Results: There were significant differences (p < 0.05) between combat groups for lumbar spine (+5.0%), dominant arm (+4.4%) BMD, and dominant and non-dominant leg LMM (+21.8% and +22.6%). Controls had significantly (p < 0.05) high adiposity (+36.8% relative), visceral adipose tissue (VAT) mass (+69.7%), VAT area (+69.5%), lower total body BMD (−8.4%) and lumbar spine BMD (−13.8%) than controls. No differences in lower limb BMD were seen in combat groups. Arm lean mass differences (dominant versus non-dominant) were significantly different between combat groups (p < 0.05, 4.2% versus 7.3%). There were no differences in punch/kick power (absolute or relative) between combat groups. 5RM strength (bench and squat) correlated significantly with upper limb striking power (r = 0.57), dominant and non-dominant leg BMD (r = 0.67, r = 0.70, respectively) and total body BMD (r = 0.59). Conclusion: BMD and LMM appear to be particularly important to discriminate between dominant and non-dominant upper limbs and less so for lower limb dominance in recreational combat athletes.


2004 ◽  
Vol 287 (4) ◽  
pp. E739-E743 ◽  
Author(s):  
Burton F. Holmes ◽  
David B. Lang ◽  
Morris J. Birnbaum ◽  
James Mu ◽  
G. Lynis Dohm

An acute bout of exercise increases muscle GLUT4 mRNA in mice, and denervation decreases GLUT4 mRNA. AMP-activated protein kinase (AMPK) activity in skeletal muscle is also increased by exercise, and GLUT4 mRNA is increased in mouse skeletal muscle after treatment with AMPK activator 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside(AICAR). These findings suggest that AMPK activation might be responsible for the increase in GLUT4 mRNA expression in response to exercise. To investigate the role of AMPK in GLUT4 regulation in response to exercise and denervation, transgenic mice with a mutated AMPK α-subunit (dominant negative; AMPK-DN) were studied. GLUT4 did not increase in AMPK-DN mice that were treated with AICAR, demonstrating that muscle AMPK is inactive. Exercise (two 3-h bouts of treadmill running separated by 1 h of rest) increased GLUT4 mRNA in both wild-type and AMPK-DN mice. Likewise, denervation decreased GLUT4 mRNA in both wild-type and AMPK-DN mice. GLUT4 mRNA was also increased by AICAR treatment in both the innervated and denervated muscles. These data demonstrate that AMPK is not required for the response of GLUT4 mRNA to exercise and denervation.


1993 ◽  
Vol 75 (5) ◽  
pp. 2125-2133 ◽  
Author(s):  
A. R. Coggan ◽  
A. M. Abduljalil ◽  
S. C. Swanson ◽  
M. S. Earle ◽  
J. W. Farris ◽  
...  

To examine effects of aging and endurance training on human muscle metabolism during exercise, 31P magnetic resonance spectroscopy was used to study the metabolic response to exercise in young (21–33 yr) and older (58–68 yr) untrained and endurance-trained men (n = 6/group). Subjects performed graded plantar flexion exercise with the right leg, with metabolic responses measured using a 31P surface coil placed over the lateral head of the gastrocnemius muscle. Muscle biopsy samples were also obtained for determination of citrate synthase activity. Rate of increase in P(i)-to-phosphocreatine ratio with increasing power output was greater (P < 0.01) in older untrained [0.058 +/- 0.022 (SD) W-1] and trained men (0.042 +/- 0.010 W-1) than in young untrained (0.038 +/- 0.017 W-1) and trained men (0.024 +/- 0.010 W-1). Plantar flexor muscle cross-sectional area and volume (determined using 1H magnetic resonance imaging) were 11–12% (P < 0.05) and 16–18% (P < 0.01) smaller, respectively, in older men. When corrected for this difference in muscle mass, age-related differences in metabolic response to exercise were reduced by approximately 50% but remained significant (P < 0.05). Citrate synthase activity was approximately 20% lower (P < 0.001) in older untrained and trained men than in corresponding young groups and was inversely related to P(i)-phosphocreatine slope (r = -0.63, P < 0.001). Age-related reductions in exercise capacity were associated with an altered muscle metabolic response to exercise, which appeared to be due to smaller muscle mass and lower muscle respiratory capacity of older subjects.(ABSTRACT TRUNCATED AT 250 WORDS)


Circulation ◽  
2016 ◽  
Vol 133 (suppl_1) ◽  
Author(s):  
Margaret A Crawford ◽  
Matthew A Allison ◽  
Michael H Criqui ◽  
Britta A Larsen

Introduction: Higher volume of coronary arterial calcium (CAC) and abdominal aortic calcium (AAC) are predictive of incident CVD, while higher density of CAC and AAC are associated with lower risk. The purpose of the present study was to determine the associations of abdominal lean muscle mass (ALMM) with CAC volume, CAC density, AAC volume, and AAC density. Hypothesis: We hypothesized that abdominal muscle mass would be negatively associated with CAC and AAC volume but positively associated with CAC and AAC density. Methods: The current study analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA) in those participants who underwent abdominal computed tomography (CT) to assess for AAC, which was also analyzed for volumes of fat (visceral and subcutaneous) and ALMM (psoas, rectus abdominis, obliques, and paraspinus). CAC and AAC were scored separately, for density and for volume. Results: Analyses were restricted to participants who had non-zero CAC or AAC volumes. The sample sizes for the CAC analyses and AAC analyses were 963 and 1283 subjects, respectively. For the CAC analyses, 39.4% (379 of 963) were female and the mean age was 66.4 years. Mean ± SD CAC volume was 218.52 ± 344.19 (range 2.34- 3244.77 mm 3 ) ; Mean ± SD CAC density was 2.70 ± .72 (range 0.83- 4.0 Hu category units). Mean ± SD AAC volume was 1402.33 ± 1888 (range 4.68- 15822.2 mm 3 ); mean ± SD AAC density was 3.02 ± .63 (range 0.83- 4.0 Hu category units). In multivariable linear regression models that controlled for age, race, gender, CVD risk factors, visceral fat, and liver and kidney markers, both CAC and AAC density were found to be significantly associated with abdominal lean muscle mass. For every 100 cm 2 increase of ALMM, CAC density decreased by .35 Hu category units (p < .05). For every 100 cm 2 increase of ALMM, AAC density decreased by .26 Hu category units (p < .05). Conversely, CAC and AAC volume were not significantly associated with abdominal lean muscle mass in final models. Conclusion: Higher levels of ALMM were associated with lower CAC and AAC density, but not volume. Contrary to expectation, we found an inverse association of ALMM with CAC and AAC density, independent of relevant CVD risk factors.


2020 ◽  
Vol 106 (1) ◽  
pp. 174-187
Author(s):  
Rowan S Hardy ◽  
Hannah Botfield ◽  
Keira Markey ◽  
James L Mitchell ◽  
Zerin Alimajstorovic ◽  
...  

Abstract Background The enzyme 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) determines prereceptor metabolism and activation of glucocorticoids within peripheral tissues. Its dysregulation has been implicated in a wide array of metabolic diseases, leading to the development of selective 11β-HSD1 inhibitors. We examined the impact of the reversible competitive 11β-HSD1 inhibitor, AZD4017, on the metabolic profile in an overweight female cohort with idiopathic intracranial hypertension (IIH). Methods We conducted a UK multicenter phase II randomized, double-blind, placebo-controlled trial of 12-week treatment with AZD4017. Serum markers of glucose homeostasis, lipid metabolism, renal and hepatic function, inflammation and androgen profiles were determined and examined in relation to changes in fat and lean mass by dual-energy X-ray absorptiometry. Results Patients receiving AZD4017 showed significant improvements in lipid profiles (decreased cholesterol, increased high-density lipoprotein [HDL] and cholesterol/HDL ratio), markers of hepatic function (decreased alkaline phosphatase and gamma-glutamyl transferase), and increased lean muscle mass (1.8%, P &lt; .001). No changes in body mass index, fat mass, and markers of glucose metabolism or inflammation were observed. Patients receiving AZD4017 demonstrated increased levels of circulating androgens, positively correlated with changes in total lean muscle mass. Conclusions These beneficial metabolic changes represent a reduction in risk factors associated with raised intracranial pressure and represent further beneficial therapeutic outcomes of 11β-HSD1 inhibition by AZD4017 in this overweight IIH cohort. In particular, beneficial changes in lean muscle mass associated with AZD4017 may reflect new applications for this nature of inhibitor in the management of conditions such as sarcopenia.


2019 ◽  
Vol 10 (4) ◽  
pp. 748-755 ◽  
Author(s):  
Douglas W. Gould ◽  
Emma L. Watson ◽  
Thomas J. Wilkinson ◽  
Joanne Wormleighton ◽  
Soteris Xenophontos ◽  
...  

2007 ◽  
Vol 2 (2) ◽  
pp. 128-136 ◽  
Author(s):  
David V.B. James ◽  
Leigh E. Sandals ◽  
Stephen B. Draper ◽  
Sara Maldonado-Martín ◽  
Dan M. Wood

Purpose:Previously it has been observed that, in well-trained 800-m athletes, VO2max is not attained during middle-distance running events on a treadmill, even when a race-type pacing strategy is adopted. Therefore, the authors investigated whether specialization in a particular running distance (400-m or 800-m) influences the VO2 attained during running on a treadmill.Methods:Six 400-m and six 800-m running specialists participated in the study. A 400-m trial and a progressive test to determine VO2max were completed in a counterbalanced order. Oxygen uptakes attained during the 400-m trial were compared to examine the influence of specialist event.Results:A VO2 plateau was observed in all participants for the progressive test, demonstrating the attainment of VO2max. The VO2max values were 56.2 ± 4.7 and 69.3 ± 4.5 mL · kg−1 · min−1 for the 400-m- and 800-m-event specialists, respectively (P = .0003). Durations for the 400-m trial were 55.1 ± 4.2 s and 55.8 ± 2.3 s for the 400-m- and 800-m-event specialists, respectively. The VO2 responses achieved were 93.1% ± 2.0% and 85.7% ± 3.0% VO2max for the 400-m- and 800-m-event specialists, respectively (P = .001).Conclusions:These results demonstrate that specialist running events do appear to influence the percentage of VO2max achieved in the 400-m trial, with the 800-m specialists attaining a lower percentage of VO2max than the 400-m specialists. The 400-m specialists appear to compensate for a lower VO2max by attaining a higher percentage VO2max during a 400-m trial.


Author(s):  
Alon Eliakim ◽  
Dan Nemet

The complex endocrine response to exercise in children and adolescents includes significant changes in hormones that regulate muscle adaptations and growth. Better understanding of this system makes the possible use of hormonal changes as an objective tool to gauge exercise intensity and duration, to assess training response, and to improve our understanding of the beneficial and deleterious hormonal effects of competitive sports (e.g. on growth and reproduction). Moreover, better understanding of the unique relationship between exercise and the endocrine system is important not only for children and adolescents engaged in competitive sports, but also to those with chronic diseases and disabilities who wish or need to increase their physical activity levels. The effect of a single exercise bout on the endocrine system and in particularly on the GH-IGF-I axis, the reproductive system, and the adrenal gland is discussed.


2011 ◽  
Vol 23 (1) ◽  
pp. 36-48 ◽  
Author(s):  
Danielle M. Lambrick ◽  
Ann V. Rowlands ◽  
Roger G. Eston

This study assessed the nature of the perceived exertion response to treadmill running in 14 healthy 7–8 year-old children, using the Eston-Parfitt (E-P) Ratings of Perceived Exertion (RPE) scale and a marble dropping task. For the E-P scale and the marble dropping task, the relationships between the RPE and work rate were best described as linear (R2 = .96) and curvilinear (R2 = .94), respectively. This study further suggests that individual respiratory-metabolic cues (oxygen uptake: O2, heart rate: HR, ventilation: V̇E) may significantly influence the overall RPE to varying degrees in young children. The E-P scale provides an intuitively meaningful and valid means of quantifying the overall perception of exertion in young, healthy children during treadmill running. The marble dropping task is a useful secondary measure of perceived exertion, which provides further insight into the nature of the perceived exertion response to exercise in young children.


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