Testosterone does not affect agrin cleavage in mobility‐limited older men despite improvement in physical function

Gagliano‐Jucá, Thiago; Storer, Thomas W.; Pencina, Karol M.; Travison, Thomas G.; Li, Zihan; Huang, Grace; Hettwer, Stefan; Dahinden, Pius; Bhasin, Shalender; Basaria, Shehzad

doi:10.1111/andr.12424

Cited by 14 publications

(25 citation statements)

References 44 publications

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“…The randomized controlled trials (RCTs) published since 2010 are summarized in Table 2 [ 50 , 65 , 66 , 67 , 68 , 69 , 70 , 71 , 72 , 73 , 74 , 75 , 76 , 77 , 78 , 79 , 80 , 81 , 82 ]. Their results varied by target population, type of testosterone formulation, and testosterone dosage.…”

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

“…Their results varied by target population, type of testosterone formulation, and testosterone dosage. Many of the RCTs investigated the effects on muscle of TRT among men with low to normal testosterone levels and 15 of 19 RCTs supported certain merits of TRT on muscle volume [ 50 , 67 , 68 , 69 , 70 , 72 , 73 , 74 , 75 , 76 , 77 , 79 , 80 , 81 , 82 ]. The other four studies, however, failed to demonstrate that TRT contributes to improving muscle mass or strength [ 65 , 66 , 71 , 78 ].…”

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

“…However, there are limited data currently available regarding the direct effects of TRT on preventing sarcopenia, which is diagnosed based on muscle mass, strength, and physical functions, and the conclusions drawn from those data have been conflicting [ 50 , 69 , 72 , 80 ]. Two RCTs demonstrated that TRT contributed to an improvement in both muscle mass/strength and physical performance [ 69 , 72 ]. However, a previous study that included 209 hypogonadal men with mobility limitations reported that 6 months of TRT could increase muscle strength and stair-climbing power but could not improve walking speed [ 80 ].…”

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

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Relationship between Testosterone and Sarcopenia in Older-Adult Men: A Narrative Review

Shigehara

Kato

Izumi

et al. 2022

JCM

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Age-related decline in testosterone is known to be associated with various clinical symptoms among older men and it is possible that the accompanying decline in muscle mass and strength might lead to a decline in motor and physical functions. Sarcopenia is an important pathophysiological factor associated with frailty in older adults and is diagnosed in older adults as a decrease in muscle strength, muscle mass, and walking speed, which can lead to a significant decline in the quality of life and shortened healthy life expectancy. Testosterone directly interacts with the androgen receptor expressed in myonuclei and satellite cells and is also indirectly associated with muscle metabolism through various cytokines and molecules. Currently, significant correlations between testosterone and frailty in men have been confirmed by numerous cross-sectional studies. Many randomized control studies have also supported the beneficial effect of testosterone replacement therapy (TRT) on muscle volume and strength among men with low to normal testosterone levels. In the world’s aging society, TRT can be a tool for preventing the onset of sarcopenia in older-adult men. This narrative review aims to show the relationship between the decline in testosterone with age, sarcopenia, and frailty, as well as the effects of testosterone replacement therapy on muscle mass and strength.

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Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

Section: Efficacy Of Testosterone Replacement Therapy For Sarcopeniamentioning

confidence: 99%

See 2 more Smart Citations

Relationship between Testosterone and Sarcopenia in Older-Adult Men: A Narrative Review

Shigehara

Kato

Izumi

et al. 2022

JCM

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“…On the contrary, Gagliano‐Jucá et al 56 observed a raise in CAF concentration over 6 months in frail, old individuals; interestingly, testosterone administration was not able to prevent such raise, despite increasing muscle strength. The authors suggested that this hormone exploits pathways other than a restore in NMJ stability to induce force ameliorations 56 …”

Section: Caf Assessment: Which Conditions and Which Results?mentioning

confidence: 89%

C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

Monti

Sarto

Sartori

et al. 2023

J cachexia sarcopenia muscle

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Ageing is accompanied by an inexorable loss of muscle mass and functionality and represents a major risk factor for numerous diseases such as cancer, diabetes and cardiovascular and pulmonary diseases. This progressive loss of muscle mass and function may also result in the insurgence of a clinical syndrome termed sarcopenia, exacerbated by inactivity and disease. Sarcopenia and muscle weakness yield the risk of falls and injuries, heavily impacting on health and social costs. Thus, screening, monitoring and prevention of conditions inducing muscle wasting and weakness are essential to improve life quality in the ageing modern society. To this aim, the reliability of easily accessible and non-invasive bloodderived biomarkers is being evaluated. C-terminal agrin fragment (CAF) has been widely investigated as a neuromuscular junction (NMJ)-related biomarker of muscle dysfunction. This narrative review summarizes and critically discusses, for the first time, the studies measuring CAF concentration in young and older, healthy and diseased individuals, cross-sectionally and in response to inactivity and physical exercise, providing possible explanations behind the discrepancies observed in the literature. To identify the studies investigating CAF in the above-mentioned conditions, all the publications found in PubMed, written in English and measuring this biomarker in blood from 2013 (when CAF was firstly measured in human serum) to 2022 were included in this review. CAF increases with age and in sarcopenic individuals when compared with age-matched, non-sarcopenic peers. In addition, CAF was found to be higher than controls in other muscle wasting conditions, such as diabetes, COPD, chronic heart failure and stroke, and in pancreatic and colorectal cancer cachectic patients. As agrin is also expressed in kidney glomeruli, chronic kidney disease and transplantation were shown to have a profound impact on CAF independently from muscle wasting. CAF concentration raises following inactivity and seems to be lowered or maintained by exercise training. Finally, CAF was reported to be cross-sectionally correlated to appendicular lean mass, handgrip and gait speed; whether longitudinal changes in CAF are associated with those in muscle mass or performance following physical exercise is still controversial. CAF seems a reliable marker to assess muscle wasting in ageing and disease, also correlating with measurements of appendicular lean mass and muscle function. Future research should aim at enlarging sample size and accurately reporting the medical history of each patient, to normalize for any condition, including chronic kidney disease, that may influence the circulating concentration of this biomarker.

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Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

Monti

Tagliaferri

Zampieri

et al. 2023

J cachexia sarcopenia muscle

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Background Ageing is accompanied by a progressive loss of skeletal muscle mass and strength, potentially determining the insurgence of sarcopenia. Evidence suggests that motoneuron and neuromuscular junction (NMJ) degeneration contribute to sarcopenia pathogenesis. Seeking for strategies able to slow down sarcopenia insurgence and progression, we investigated whether a 2-year mixed-model training involving aerobic, strength and balance exercises would be effective for improving or preserving motoneuronal health and NMJ stability, together with muscle mass, strength and functionality in an old, sarcopenic population. Methods Forty-five sarcopenic elderly (34 females; 11 males) with low dual-energy X-ray absorptiometry (DXA) lean mass and Short Physical Performance Battery (SPPB) score <9 were randomly assigned to either a control group [Healthy Aging Lifestyle Education (HALE), n = 21] or an intervention group [MultiComponent Intervention (MCI), n = 24]. MCI trained three times per week for 2 years with a mix of aerobic, strength and balance exercises matched with nutritional advice. Before and after the intervention, ultrasound scans of the vastus lateralis (VL), SPPB and a blood sample were obtained. VL architecture [pennation angle (PA) and fascicle length (Lf)] and cross-sectional area (CSA) were measured. As biomarkers of neuronal health and NMJ stability status, neurofilament light chain (NfL) and C-terminal agrin fragment (CAF) concentrations were measured in serum. Differences in ultrasound parameters, NfL and CAF concentration and physical performance between baseline and follow-up were tested with mixed ANOVA or Wilcoxon test. The relationship between changes in physical performance and NfL or CAF concentration was assessed through correlation analyses. Results At follow-up, MCI showed preserved VL architecture (PA, Lf) despite a reduced CSA (À8.4%, P < 0.001), accompanied by maintained CAF concentration and ameliorated overall SPPB performance (P = 0.007). Conversely, HALE showed 12.7% decrease in muscle CSA (P < 0.001), together with 5.1% and 5.5% reduction in PA and Lf (P < 0.001 and P = 0.001, respectively), and a 6.2% increase in CAF (P = 0.009) but improved SPPB balance score (P = 0.007). NfL concentration did not change in either group. In the population, negative correlations between changes in CAF concentration and SPPB total score were found (P = 0.047), whereas no correlation between NfL and SPPB variations was observed. Conclusions The present findings suggest that our 2-year mixed aerobic, strength and balance training seemed effective for preventing the age and sarcopenia-related increases in CAF concentration, preserving NMJ stability as well as muscle structure (PA and Lf) and improving physical performance in sarcopenic older individuals.

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Testosterone does not affect agrin cleavage in mobility‐limited older men despite improvement in physical function

Cited by 14 publications

References 44 publications

Relationship between Testosterone and Sarcopenia in Older-Adult Men: A Narrative Review

Relationship between Testosterone and Sarcopenia in Older-Adult Men: A Narrative Review

C‐terminal agrin fragment as a biomarker of muscle wasting and weakness: a narrative review

Effects of a 2‐year exercise training on neuromuscular system health in older individuals with low muscle function

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