Losartan has no additive effect on the response to heavy-resistance exercise in human elderly skeletal muscle

Heisterberg, Mette Flindt; Andersen, Jesper L.; Schjerling, Peter; Lund, Alberte; Dalskov, Simone; Jønsson, Anders Overgård; Warming, Nichlas; Fogelstrøm, Mathilde; Kjær, Michael; Mackey, Abigail L.

doi:10.1152/japplphysiol.00106.2018

Cited by 19 publications

(44 citation statements)

References 69 publications

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“…With increasing age there is a well‐established decrease in muscle fibers and fiber CSA, the latter being more pronounced in the type 2 fibers . This was confirmed in the present study as there were significant, negative correlations between age and maximal isometric torque, type 2 muscle fiber CSA, and quadriceps CSA, with no significant relationship for type 1 muscle fiber CSA.…”

Section: Discussionsupporting

confidence: 88%

“…One possible explanation for this is that it is basically unknown whether the expression of these markers gradually accumulates with increasing age or whether they follow a different trajectory. Because muscle fiber denervation has been observed to increase severely in the ninth decade of life, it could be that it is only at such a high age, above the age range of most of our participants, that these markers increase beyond the ~1.0% that we observed.…”

Section: Discussionmentioning

confidence: 74%

“…This study arose from a study previously conducted at the Institute of Sports Medicine, Copenhagen, which was approved by The Committees on Health Research Ethics for the Capital Region of Denmark (Reference: H‐15005761) and conformed to the standards set by the Declaration of Helsinki. Volunteers gave written informed consent before inclusion.…”

Section: Methodsmentioning

confidence: 99%

“…Cholesterol medicine and vitamin supplements were allowed. Muscle fiber type and size have previously been reported for most participants . After inclusion the participants underwent the following three tests, described in detail elsewhere: (a) MRI of the thighs with a Philips Ingenia 3.0 T scanner to asses quadriceps cross‐sectional area (CSA), (b) whole‐body dual energy x‐ray absorptiometry (Lunar iDXA; GE Medical Systems, Pewaukee, Wisconsin) with lean body mass (LBM) as the primary output, (c) measurement of the 70° knee‐angle quadriceps maximal isometric torque with a Kin‐Com dynamometer (Kinetic 359 Communicator, model 500–11; Chattecx, Chattanooga, Tennessee).…”

Section: Methodsmentioning

confidence: 99%

“…This study arose from a study previously conducted at the Institute of Sports Medicine, Copenhagen, 29 Between all steps, slides were washed in two changes of 0.05 M Trisbuffered saline. Slides were stored in a dark at room temperature for 24 to 48 hours and moved to −20 C until analysis.…”

Section: Methodsmentioning

confidence: 99%

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Molecular indicators of denervation in aging human skeletal muscle

et al. 2019

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Introduction Muscle fiber denervation increases with age, yet studies at the tissue level are sparse due to the challenging nature of establishing the relative role of regeneration and denervation. Methods Muscle biopsies were obtained from the vastus lateralis of 70 healthy men (aged 72 ± 6 years; range, 65–94). Messenger RNA (mRNA) levels of acetylcholine receptors (AchR) were measured, and sections were stained for embryonic myosin, neonatal myosin (MHCn), and neural cell adhesion molecule (NCAM). Results Embryonic myosin+ fibers were rare, while MHCn+ and NCAM+ fibers were observed in all samples. Age (range, 65–94 years) was negatively associated with AchRγ mRNA. Discussion Muscle from healthy older individuals expressed developmental myosins to varying degrees but more than has been previously reported for young individuals. Along with the AchR correlations, we propose that these findings support the presence of neuromuscular junction destabilization, denervation, and reinnervation in aging human skeletal muscle.

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Section: Discussionsupporting

confidence: 88%

Section: Discussionmentioning

confidence: 74%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Molecular indicators of denervation in aging human skeletal muscle

et al. 2019

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Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Achison

Adamson

Akpan

et al. 2022

J cachexia sarcopenia muscle

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Background This trial aimed to determine the efficacy of leucine and/or perindopril in improving physical function in older people with sarcopenia. Methods Placebo‐controlled, parallel group, double‐blind, randomized two‐by‐two factorial trial. We recruited adults aged ≥ 70 years with sarcopenia, defined as low gait speed (<0.8 m/s on 4 m walk) and/or low handgrip strength (women < 20 kg, men < 30 kg) plus low muscle mass (using sex and body mass index category‐specific thresholds derived from normative UK BioBank data) from 14 UK centres. Eligible participants were randomized to perindopril 4 mg or placebo, and to oral leucine powder 2.5 g or placebo thrice daily. The primary outcome was the between‐group difference in the short physical performance battery (SPPB) score over 12‐month follow‐up by repeated‐measures mixed models. Results were combined with existing systematic reviews using random‐effects meta‐analysis to derive summary estimates of treatment efficacy. Results We screened 320 people and randomized 145 participants compared with an original target of 440 participants. For perindopril [n = 73, mean age 79 (SD 6), female sex 39 (53%), mean SPPB 7.1 (SD 2.3)] versus no perindopril [n = 72, mean age 79 (SD 6), female sex 39 (54%), mean SPPB 6.9 (SD 2.4)], median adherence to perindopril was lower (76% vs. 96%; P < 0.001). Perindopril did not improve the primary outcome [adjusted treatment effect −0.1 points (95%CI −1.2 to 1.0), P = 0.89]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect −0.4 kg (95%CI −1.1 to 0.3), P = 0.27]. More adverse events occurred in the perindopril group (218 vs. 165), but falls rates were similar. For leucine [n = 72, mean age 78 (SD 6), female sex 38 (53%), mean SPPB 7.0 (SD 2.1)] versus no leucine [n = 72, mean age 79 (SD 6), female sex 40 (55%), mean SPPB 7.0 (SD 2.5)], median adherence was the same in both groups (76% vs. 76%; P = 0.99). Leucine did not improve the primary outcome [adjusted treatment effect 0.1 point (95%CI −1.0 to 1.1), P = 0.90]. No significant treatment benefit was seen for any secondary outcome including muscle mass [adjusted treatment effect −0.3 kg (95%CI −1.0 to 0.4), P = 0.47]. Meta‐analysis of angiotensin converting enzyme inhibitor/angiotensin receptor blocker trials showed no clinically important treatment effect for the SPPB [between‐group difference −0.1 points (95%CI −0.4 to 0.2)]. Conclusions Neither perindopril nor leucine improved physical performance or muscle mass in this trial; meta‐analysis did not find evidence of efficacy of either ACE inhibitors or leucine as treatments to improve physical performance.

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Marked irregular myofiber shape is a hallmark of human skeletal muscle ageing and is reversed by heavy resistance training

Soendenbroe,

Karlsen,

Svensson

et al. 2023

J cachexia sarcopenia muscle

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BackgroundAge‐related loss of strength is disproportionally greater than the loss of mass, suggesting maladaptations in the neuro‐myo‐tendinous system. Myofibers are often misshaped in aged and diseased muscle, but systematic analyses of large sample sets are lacking. Our aim was to investigate myofiber shape in relation to age, exercise, myofiber type, species and sex.MethodsVastus lateralis muscle biopsies (n = 265) from 197 males and females, covering an age span of 20–97 years, were examined. The gastrocnemius and soleus muscles of 11 + 22‐month‐old male C57BL/6 mice were also examined. Immunofluorescence and ATPase stainings of muscle cross‐sections were used to measure myofiber cross‐sectional area (CSA) and perimeter. From these, a shape factor index (SFI) was calculated in a fibre‐type‐specific manner (type I/II in humans; type I/IIa/IIx/IIb in mice), with higher values indicating increased deformity. Heavy resistance training (RT) was performed three times per week for 3–4 months by a subgroup (n = 59). Correlation analyses were performed comparing SFI and CSA with age, muscle mass, maximal voluntary contraction (MVC), rate of force development and specific force (MVC/muscle mass).ResultsIn human muscle, SFI was positively correlated with age for both type I (R2 = 0.20) and II (R2 = 0.38) myofibers. When subjects were separated into age cohorts, SFI was lower for type I (4%, P < 0.001) and II (6%, P < 0.001) myofibers in young (20–36) compared with old (60–80) and higher for type I (5%, P < 0.05) and II (14%, P < 0.001) myofibers in the oldest old (>80) compared with old. The increased SFI in old muscle was observed in myofibers of all sizes. Within all three age cohorts, type II myofiber SFI was higher than that for type I myofiber (4–13%, P < 0.001), which was also the case in mice muscles (8–9%, P < 0.001). Across age cohorts, there was no difference between males and females in SFI for either type I (P = 0.496/0.734) or II (P = 0.176/0.585) myofibers. Multiple linear regression revealed that SFI, after adjusting for age and myofiber CSA, has independent explanatory power for 8/10 indices of muscle mass and function. RT reduced SFI of type II myofibers in both young and old (3–4%, P < 0.001).ConclusionsHere, we identify type I and II myofiber shape in humans as a hallmark of muscle ageing that independently predicts volumetric and functional assessments of muscle health. RT reverts the shape of type II myofibers, suggesting that a lack of myofiber recruitment might lead to myofiber deformity.

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Losartan has no additive effect on the response to heavy-resistance exercise in human elderly skeletal muscle

Abstract: There does not appear to be any effect of AT1R blocking in elderly men during four months of resistance training. Therefore, we do not find any support for using AT1R blockers for promoting muscle adaptation to training in humans.

Cited by 19 publications

References 69 publications

Molecular indicators of denervation in aging human skeletal muscle

Molecular indicators of denervation in aging human skeletal muscle

Effect of perindopril or leucine on physical performance in older people with sarcopenia: the LACE randomized controlled trial

Marked irregular myofiber shape is a hallmark of human skeletal muscle ageing and is reversed by heavy resistance training

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