Wilbert P Vermeij, Khalid Alyodawi, Ivar van Galen, Jennie L von der Heide, María B Birkisdóttir, Lisanne J Van't Sant, Rutger A Ozinga, Daphne S J Komninos, Kimberly Smit, Yvonne M A Rijksen, Renata M C Brandt, Sander Barnhoorn, Dick Jaarsma, Sathivel Vaiyapuri, Olli Ritvos, Tobias B Huber, Oliver Kretz, Ketan Patel
Background: Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well-established long-term intervention recognized for its universal anti-ageing effects. DR temporarily suppresses growth, and when applied to progeroid DNA repair-deficient mice doubles lifespan with systemic health benefits. Counterintuitively, attenuation of myostatin/activin signalling by soluble activin receptor (sActRIIB), boosts the growth of muscle and, in these animals, prevents muscle wasting, improves kidney functioning, and compresses morbidity.
Methods: Here, we investigated a combined approach, applying an anabolic regime (sActRIIB) at the same time as DR to Ercc1Δ/- progeroid mice. Following both single treatments and combined, we monitored global effects on body weight, lifespan and behaviour, and local effects on muscle and tissue weight, muscle morphology and function, and ultrastructural and transcriptomic changes in muscle and kidney.
Results: Lifespan was mostly influenced by DR (extended from approximately 20 to 40 weeks; P < 0.001), with sActRIIB clearly increasing muscle mass (35-65%) and tetanic force (P < 0.001). The combined regime yielded a stable uniform body weight, but increased compared with DR alone, synergistically improved motor coordination and further delayed the onset and development of balance problems. sActRIIB significantly increased muscle fibre size (P < 0.05) in mice subjected to DR and lowered all signs of muscle damage. Ercc1Δ/- mice showed abnormal neuromuscular junctions. Single interventions by sActRIIB treatment or DR only partially rescued this phenotype, while in the double intervention group, the regularly shaped junctional foldings were maintained. In kidney of Ercc1Δ/- mice, we observed a mild but significant foot process effacement, which was restored by either intervention. Transcriptome analysis also pointed towards reduced levels of DNA damage in muscle and kidney by DR, but not sActRIIB, while these levels retained lower in the double intervention.
Conclusions: In muscle, we found synergistic effects of combining sActRIIB with DR, but not in kidney, with an overall better health in the double intervention group. Crucially, the benefits of each single intervention are not lost when administered in combination, but rather strengthened, even when sActRIIB was applied late in life, opening opportunities for translation to human.
背景:衰老是一个复杂的多因素过程,影响到所有器官和组织,而 DNA 损伤积累是一个共同的根本原因。为了延缓衰老,人们在模式生物中应用了各种策略,并评估了这些策略对健康和寿命的益处。饮食限制(DR,又称热量限制)是一种行之有效的长期干预措施,因其普遍的抗衰老效果而得到认可。DR 可暂时抑制生长,应用于早衰 DNA 修复缺陷小鼠时,可使寿命延长一倍,并对全身健康有益。与直觉相反,可溶性激活素受体(sActRIIB)可抑制肌生长蛋白/激活素信号,促进肌肉生长,并在这些动物中防止肌肉萎缩、改善肾功能和降低发病率。方法:在此,我们研究了一种综合方法,即在对 Ercc1Δ/- 类早衰小鼠进行 DR 治疗的同时应用合成代谢机制(sActRIIB)。在单一治疗和联合治疗后,我们监测了对体重、寿命和行为的整体影响,以及对肌肉和组织重量、肌肉形态和功能、肌肉和肾脏超微结构和转录组变化的局部影响:寿命主要受DR的影响(从大约20周延长到40周;P Δ/-小鼠表现出异常的神经肌肉接头。sActRIIB 处理或 DR 的单次干预只能部分缓解这种表型,而在双重干预组中,规则形状的连接皱褶得以保持。在 Ercc1Δ/- 小鼠的肾脏中,我们观察到了轻微但显著的足突脱出现象,无论采用哪种干预方法,这种现象都能得到恢复。转录组分析还表明,DR降低了肌肉和肾脏中的DNA损伤水平,但sActRIIB没有降低,而这些水平在双重干预中保持较低水平:在肌肉中,我们发现了 sActRIIB 与 DR 的协同作用,但在肾脏中却没有发现,双重干预组的总体健康状况更好。最重要的是,每种单一干预措施的益处在联合应用时不仅没有丧失,反而得到了加强,即使是在生命晚期应用 sActRIIB 也是如此,这为向人类转化提供了机会。
{"title":"Improved health by combining dietary restriction and promoting muscle growth in DNA repair-deficient progeroid mice.","authors":"Wilbert P Vermeij, Khalid Alyodawi, Ivar van Galen, Jennie L von der Heide, María B Birkisdóttir, Lisanne J Van't Sant, Rutger A Ozinga, Daphne S J Komninos, Kimberly Smit, Yvonne M A Rijksen, Renata M C Brandt, Sander Barnhoorn, Dick Jaarsma, Sathivel Vaiyapuri, Olli Ritvos, Tobias B Huber, Oliver Kretz, Ketan Patel","doi":"10.1002/jcsm.13570","DOIUrl":"https://doi.org/10.1002/jcsm.13570","url":null,"abstract":"<p><strong>Background: </strong>Ageing is a complex multifactorial process, impacting all organs and tissues, with DNA damage accumulation serving as a common underlying cause. To decelerate ageing, various strategies have been applied to model organisms and evaluated for health and lifespan benefits. Dietary restriction (DR, also known as caloric restriction) is a well-established long-term intervention recognized for its universal anti-ageing effects. DR temporarily suppresses growth, and when applied to progeroid DNA repair-deficient mice doubles lifespan with systemic health benefits. Counterintuitively, attenuation of myostatin/activin signalling by soluble activin receptor (sActRIIB), boosts the growth of muscle and, in these animals, prevents muscle wasting, improves kidney functioning, and compresses morbidity.</p><p><strong>Methods: </strong>Here, we investigated a combined approach, applying an anabolic regime (sActRIIB) at the same time as DR to Ercc1<sup>Δ/-</sup> progeroid mice. Following both single treatments and combined, we monitored global effects on body weight, lifespan and behaviour, and local effects on muscle and tissue weight, muscle morphology and function, and ultrastructural and transcriptomic changes in muscle and kidney.</p><p><strong>Results: </strong>Lifespan was mostly influenced by DR (extended from approximately 20 to 40 weeks; P < 0.001), with sActRIIB clearly increasing muscle mass (35-65%) and tetanic force (P < 0.001). The combined regime yielded a stable uniform body weight, but increased compared with DR alone, synergistically improved motor coordination and further delayed the onset and development of balance problems. sActRIIB significantly increased muscle fibre size (P < 0.05) in mice subjected to DR and lowered all signs of muscle damage. Ercc1<sup>Δ/-</sup> mice showed abnormal neuromuscular junctions. Single interventions by sActRIIB treatment or DR only partially rescued this phenotype, while in the double intervention group, the regularly shaped junctional foldings were maintained. In kidney of Ercc1<sup>Δ/-</sup> mice, we observed a mild but significant foot process effacement, which was restored by either intervention. Transcriptome analysis also pointed towards reduced levels of DNA damage in muscle and kidney by DR, but not sActRIIB, while these levels retained lower in the double intervention.</p><p><strong>Conclusions: </strong>In muscle, we found synergistic effects of combining sActRIIB with DR, but not in kidney, with an overall better health in the double intervention group. Crucially, the benefits of each single intervention are not lost when administered in combination, but rather strengthened, even when sActRIIB was applied late in life, opening opportunities for translation to human.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142152725","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young-Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee
Background: Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics.
Methods: After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort.
Results: Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799).
Conclusions: SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.
{"title":"Sphingolipid metabolites as potential circulating biomarkers for sarcopenia in men.","authors":"Je Hyun Seo, Jung-Min Koh, Han Jin Cho, Hanjun Kim, Young-Sun Lee, Su Jung Kim, Pil Whan Yoon, Won Kim, Sung Jin Bae, Hong-Kyu Kim, Hyun Ju Yoo, Seung Hun Lee","doi":"10.1002/jcsm.13582","DOIUrl":"https://doi.org/10.1002/jcsm.13582","url":null,"abstract":"<p><strong>Background: </strong>Sarcopenia is an age-related progressive loss of muscle mass and function. Sarcopenia is a multifactorial disorder, including metabolic disturbance; therefore, metabolites may be used as circulating biomarkers for sarcopenia. We aimed to investigate potential biomarkers of sarcopenia using metabolomics.</p><p><strong>Methods: </strong>After non-targeted metabolome profiling of plasma from mice of an aging mouse model of sarcopenia, sphingolipid metabolites and muscle cells from the animal model were evaluated using targeted metabolome profiling. The associations between sphingolipid metabolites identified from mouse and cell studies and sarcopenia status were assessed in men in an age-matched discovery (72 cases and 72 controls) and validation (36 cases and 128 controls) cohort; women with sarcopenia (36 cases and 36 controls) were also included as a discovery cohort.</p><p><strong>Results: </strong>Both non-targeted and targeted metabolome profiling in the experimental studies showed an association between sphingolipid metabolites, including ceramides (CERs) and sphingomyelins (SMs), and sarcopenia. Plasma SM (16:0), CER (24:1), and SM (24:1) levels in men with sarcopenia were significantly higher in the discovery cohort than in the controls (all P < 0.05). There were no significant differences in plasma sphingolipid levels for women with or without sarcopenia. In men in the discovery cohort, an area under the receiver-operating characteristic curve (AUROC) of SM (16:0) for low muscle strength and low muscle mass was 0.600 (95% confidence interval [CI]: 0.501-0.699) and 0.647 (95% CI: 0.557-0.737). The AUROC (95% CI) of CER (24:1) and SM (24:1) for low muscle mass in men was 0.669 (95% CI: 0.581-0.757) and 0.670 (95% CI: 0.582-0.759), respectively. Using a regression equation combining CER (24:1) and SM (16:0) levels, a sphingolipid (SphL) score was calculated; an AUROC of the SphL score for sarcopenia was 0.712 (95% CI: 0.626-0.798). The addition of the SphL score to HGS significantly improved the AUC from 0.646 (95% CI: 0.575-0.717; HGS only) to 0.751 (95% CI: 0.671-0.831, P = 0.002; HGS + SphL) in the discovery cohort. The predictive ability of the SphL score for sarcopenia was confirmed in the validation cohort (AUROC = 0.695, 95% CI: 0.591-0.799).</p><p><strong>Conclusions: </strong>SM (16:0), reflecting low muscle strength, and CER (24:1) and SM (16:0), reflecting low muscle mass, are potential circulating biomarkers for sarcopenia in men. Further research on sphingolipid metabolites is required to confirm these results and provide additional insights into the metabolomic changes relevant to the pathogenesis and diagnosis of sarcopenia.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wai W. Cheung, Ping Zhou, Ronghao Zheng, Arieh Gertler, Eduardo A. Oliveira, Robert H. Mak
BackgroundThe <jats:italic>CTNS</jats:italic> gene mutation causes infantile nephropathic cystinosis (INC). Patients with INC develop Fanconi syndrome and chronic kidney disease (CKD) with significant bone deformations. C57BL/6 <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice are an animal model for studying INC. Hyperleptinaemia results from the kidney's inability to eliminate the hormone leptin in CKD. <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice have elevated serum leptin concentrations. Leptin regulates bone metabolism through its receptor that signals further via the hypothalamic melanocortin 4 receptor (MC4R). Leptin signalling may affect bone health in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice.MethodsWe first defined the time course of bone abnormalities in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice between 1 and 12 months of age. We used both genetic and pharmacological approaches to investigate leptin signalling in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. We generated <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup><jats:italic>Mc4r</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> double knockout mice. Bone phenotype of <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup><jats:italic>Mc4r</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice, <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice and wild type (WT) mice at 1, 4, and 9 months of age were compared. We then treated 12‐month‐old <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice and WT mice with a pegylated leptin receptor antagonist (PLA) (7 mg/kg/day, IP), a MC4R antagonist agouti‐related peptide (AgRP) (2 nmol, intracranial infusion on days 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27), or vehicle (normal saline), respectively, for 28 days. Whole‐body (BMC/BMD, bone area) and femoral bone phenotype (BMC/BMD, bone area, length and failure load) of mice were measured by DXA and femoral shaft biochemical test. We also measured lean mass content by EchoMRI and muscle function (grip strength and rotarod activity) in mice. Femur protein content of JAK2 and STAT3 was measured by ELISA kits, respectively.ResultsBone defects are present in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice throughout its first year of life. The deletion of the <jats:italic>Mc4r</jats:italic> gene attenuated bone disorder in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. Femoral BMD, bone area, length, and strength (failure load) were significantly increased in 9‐month‐old <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></ja
{"title":"Leptin signalling altered in infantile nephropathic cystinosis‐related bone disorder","authors":"Wai W. Cheung, Ping Zhou, Ronghao Zheng, Arieh Gertler, Eduardo A. Oliveira, Robert H. Mak","doi":"10.1002/jcsm.13579","DOIUrl":"https://doi.org/10.1002/jcsm.13579","url":null,"abstract":"BackgroundThe <jats:italic>CTNS</jats:italic> gene mutation causes infantile nephropathic cystinosis (INC). Patients with INC develop Fanconi syndrome and chronic kidney disease (CKD) with significant bone deformations. C57BL/6 <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice are an animal model for studying INC. Hyperleptinaemia results from the kidney's inability to eliminate the hormone leptin in CKD. <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice have elevated serum leptin concentrations. Leptin regulates bone metabolism through its receptor that signals further via the hypothalamic melanocortin 4 receptor (MC4R). Leptin signalling may affect bone health in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice.MethodsWe first defined the time course of bone abnormalities in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice between 1 and 12 months of age. We used both genetic and pharmacological approaches to investigate leptin signalling in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. We generated <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup><jats:italic>Mc4r</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> double knockout mice. Bone phenotype of <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup><jats:italic>Mc4r</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice, <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice and wild type (WT) mice at 1, 4, and 9 months of age were compared. We then treated 12‐month‐old <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice and WT mice with a pegylated leptin receptor antagonist (PLA) (7 mg/kg/day, IP), a MC4R antagonist agouti‐related peptide (AgRP) (2 nmol, intracranial infusion on days 0, 3, 6, 9, 12, 15, 18, 21, 24, and 27), or vehicle (normal saline), respectively, for 28 days. Whole‐body (BMC/BMD, bone area) and femoral bone phenotype (BMC/BMD, bone area, length and failure load) of mice were measured by DXA and femoral shaft biochemical test. We also measured lean mass content by EchoMRI and muscle function (grip strength and rotarod activity) in mice. Femur protein content of JAK2 and STAT3 was measured by ELISA kits, respectively.ResultsBone defects are present in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice throughout its first year of life. The deletion of the <jats:italic>Mc4r</jats:italic> gene attenuated bone disorder in <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></jats:sup> mice. Femoral BMD, bone area, length, and strength (failure load) were significantly increased in 9‐month‐old <jats:italic>Ctns</jats:italic><jats:sup><jats:italic>−/−</jats:italic></ja","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100692","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Matthew Gittins, Nada AlMohaisen, Chris Todd, Simon Lal, Sorrel Burden
BackgroundIt is well reported that malnutrition in acute care is associated with poorer health outcomes including increased mortality. However, the consequences of malnutrition on survival in community settings is uncertain. Malnutrition in people 65 years or over is often cited. Nevertheless, this study includes both middle‐aged and older adults as current public health policy is highlighting the need to increase disease‐free life years and is moving away from just extending life to increase overall longevity. The aim of this study is to describe the association of the risk of malnutrition using the Malnutrition Universal Screening Tool (MUST) with mortality in community‐dwelling middle‐aged and older adults.MethodsWe used the UK Biobank to investigate the association between those at risk of malnutrition and mortality in participants aged ≥50 years. MUST identified risk of malnutrition and linked data to national death registries confirmed mortality. Years of life lost (YLL) and Cox proportional hazard models with hazard ratios (HR) and confidence intervals (CI) described risk associated with all‐cause mortality.ResultsThere were 502 408 participants recruited, 117 830 were ≤50 years leaving 384 578 eligible participants. Based on MUST scores 63 495 (16.5%) were at risk of malnutrition with 401 missing some data and excluded. Incidence of mortality for at risk participants was 755 per 100 000 person‐years, corresponding to 153 476 YLL. Of those at risk of malnutrition, 9.5% died versus 7.8% at low risk. Initial survival analysis reported an increased risk of mortality (HR 1.29, 95% CI: 1.25 to 1.33) that decreased after adjusting for confounders (HR 1.14, 95% CI: 1.11 to 1.18) in those at risk of malnutrition versus those at low risk.ConclusionsRisk of malnutrition was associated with increased overall mortality. Modest effect sizes are demonstrated but are supportive of public health policies, which advocate wide‐scale community, based nutritional screening for middle‐aged and older adults.
{"title":"Overall mortality for community‐dwelling adults over 50 years at risk of malnutrition","authors":"Matthew Gittins, Nada AlMohaisen, Chris Todd, Simon Lal, Sorrel Burden","doi":"10.1002/jcsm.13585","DOIUrl":"https://doi.org/10.1002/jcsm.13585","url":null,"abstract":"BackgroundIt is well reported that malnutrition in acute care is associated with poorer health outcomes including increased mortality. However, the consequences of malnutrition on survival in community settings is uncertain. Malnutrition in people 65 years or over is often cited. Nevertheless, this study includes both middle‐aged and older adults as current public health policy is highlighting the need to increase disease‐free life years and is moving away from just extending life to increase overall longevity. The aim of this study is to describe the association of the risk of malnutrition using the Malnutrition Universal Screening Tool (MUST) with mortality in community‐dwelling middle‐aged and older adults.MethodsWe used the UK Biobank to investigate the association between those at risk of malnutrition and mortality in participants aged ≥50 years. MUST identified risk of malnutrition and linked data to national death registries confirmed mortality. Years of life lost (YLL) and Cox proportional hazard models with hazard ratios (HR) and confidence intervals (CI) described risk associated with all‐cause mortality.ResultsThere were 502 408 participants recruited, 117 830 were ≤50 years leaving 384 578 eligible participants. Based on MUST scores 63 495 (16.5%) were at risk of malnutrition with 401 missing some data and excluded. Incidence of mortality for at risk participants was 755 per 100 000 person‐years, corresponding to 153 476 YLL. Of those at risk of malnutrition, 9.5% died versus 7.8% at low risk. Initial survival analysis reported an increased risk of mortality (HR 1.29, 95% CI: 1.25 to 1.33) that decreased after adjusting for confounders (HR 1.14, 95% CI: 1.11 to 1.18) in those at risk of malnutrition versus those at low risk.ConclusionsRisk of malnutrition was associated with increased overall mortality. Modest effect sizes are demonstrated but are supportive of public health policies, which advocate wide‐scale community, based nutritional screening for middle‐aged and older adults.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142100691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut-muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia-defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (-defining parameters) and relative abundance (RA) of GM-taxa or GM-(α- or β) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA-reporting guideline and pre-registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty-two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia-defining parameter (muscle mass, strength or physical performance). Studies found different GM-taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM-taxa. Regarding β-diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α-diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α-diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P < 0.05). Persons with sarcopenia and low muscle parameters have less rich and diverse GM and can be separated from persons with preserved muscle mass and function based on GM-composition. Sarcopenia and low muscle parameters are also associated with different GM-taxa at multiple levels, but results were heterogeneous and no causal conclusions could be made due to the cross-sectional design of the studies. This emphasizes the need for uniformly designed cross-sectional and longitudinal trials with appropriate GM confounder control in large samples of persons with sarcopenia and clearly defined core outcome sets in order to further explore changes in GM-taxa and to determine a sarcopenia-specific GM-signature.
{"title":"Associations between gut microbiota and sarcopenia or its defining parameters in older adults: A systematic review.","authors":"Laurence Lapauw, Aurélie Rutten, Jolan Dupont, Nadjia Amini, Laura Vercauteren, Muriel Derrien, Jeroen Raes, Evelien Gielen","doi":"10.1002/jcsm.13569","DOIUrl":"https://doi.org/10.1002/jcsm.13569","url":null,"abstract":"<p><p>Altered gut microbiota (GM) potentially contribute to development or worsening of sarcopenia through a gut-muscle axis. This systematic review aims to compare GM between persons with sarcopenia or low sarcopenia-defining parameters (muscle mass, strength, and physical performance) to those with preserved muscle status, as well as to clarify possible associations between sarcopenia (-defining parameters) and relative abundance (RA) of GM-taxa or GM-(α- or β) diversity indices, in order to clarify whether there is robust evidence of the existence of a GM signature for sarcopenia. This systematic review was conducted according to the PRISMA-reporting guideline and pre-registered on PROSPERO (CRD42021259597). PubMed, Web of Science, Embase, ClinicalTrials.gov, and Cochrane library were searched until 20 July 2023. Included studies reported on GM and sarcopenia or its defining parameters. Observational studies were included with populations of mean age ≥50 years. Thirty-two studies totalling 10 781 persons (58.56% ♀) were included. Thirteen studies defined sarcopenia as a construct. Nineteen studies reported at least one sarcopenia-defining parameter (muscle mass, strength or physical performance). Studies found different GM-taxa at multiple levels to be significantly associated with sarcopenia (n = 4/6), muscle mass (n = 13/14), strength (n = 7/9), and physical performance (n = 3/3); however, directions of associations were heterogeneous and also conflicting for specific GM-taxa. Regarding β-diversity, studies found GM of persons with sarcopenia, low muscle mass, or low strength to cluster differently compared with persons with preserved muscle status. α-diversity was low in persons with sarcopenia or low muscle mass as compared with those with preserved muscle status, indicating low richness and diversity. In line with this, α-diversity was significantly and positively associated with muscle mass (n = 3/4) and muscle strength (n = 2/3). All reported results were significant (P < 0.05). Persons with sarcopenia and low muscle parameters have less rich and diverse GM and can be separated from persons with preserved muscle mass and function based on GM-composition. Sarcopenia and low muscle parameters are also associated with different GM-taxa at multiple levels, but results were heterogeneous and no causal conclusions could be made due to the cross-sectional design of the studies. This emphasizes the need for uniformly designed cross-sectional and longitudinal trials with appropriate GM confounder control in large samples of persons with sarcopenia and clearly defined core outcome sets in order to further explore changes in GM-taxa and to determine a sarcopenia-specific GM-signature.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142078628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Daria Ferrara, Elisabetta M Abenavoli, Thomas Beyer, Stefan Gruenert, Marcus Hacker, Swen Hesse, Lukas Hofmann, Smilla Pusitz, Michael Rullmann, Osama Sabri, Roberto Sciagrà, Lalith Kumar Shiyam Sundar, Anke Tönjes, Hubert Wirtz, Josef Yu, Armin Frille
Background: Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [18F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC.
Methods: This multi-centre study included 345 LCP who underwent WB [18F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N = 158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N = 90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (aorta>) and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [18F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient.
Results: The three CAC categories displayed multi-organ differences in aorta>. In all target organs, aorta> was higher in the 'CAC' cohort compared with 'No CAC' (P < 0.01), except for liver and kidneys, where aorta> in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in aorta> of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ = -0.8) was identified between aorta> and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting aorta> of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'.
Conclusions: WB [18F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients
{"title":"Detection of cancer-associated cachexia in lung cancer patients using whole-body [<sup>18</sup>F]FDG-PET/CT imaging: A multi-centre study.","authors":"Daria Ferrara, Elisabetta M Abenavoli, Thomas Beyer, Stefan Gruenert, Marcus Hacker, Swen Hesse, Lukas Hofmann, Smilla Pusitz, Michael Rullmann, Osama Sabri, Roberto Sciagrà, Lalith Kumar Shiyam Sundar, Anke Tönjes, Hubert Wirtz, Josef Yu, Armin Frille","doi":"10.1002/jcsm.13571","DOIUrl":"https://doi.org/10.1002/jcsm.13571","url":null,"abstract":"<p><strong>Background: </strong>Cancer-associated cachexia (CAC) is a metabolic syndrome contributing to therapy resistance and mortality in lung cancer patients (LCP). CAC is typically defined using clinical non-imaging criteria. Given the metabolic underpinnings of CAC and the ability of [<sup>18</sup>F]fluoro-2-deoxy-D-glucose (FDG)-positron emission tomography (PET)/computer tomography (CT) to provide quantitative information on glucose turnover, we evaluate the usefulness of whole-body (WB) PET/CT imaging, as part of the standard diagnostic workup of LCP, to provide additional information on the onset or presence of CAC.</p><p><strong>Methods: </strong>This multi-centre study included 345 LCP who underwent WB [<sup>18</sup>F]FDG-PET/CT imaging for initial clinical staging. A weight loss grading system (WLGS) adjusted to body mass index was used to classify LCP into 'No CAC' (WLGS-0/1 at baseline prior treatment and at first follow-up: N = 158, 51F/107M), 'Dev CAC' (WLGS-0/1 at baseline and WLGS-3/4 at follow-up: N = 90, 34F/56M), and 'CAC' (WLGS-3/4 at baseline: N = 97, 31F/66M). For each CAC category, mean standardized uptake values (SUV) normalized to aorta uptake (<SUV<sub>aorta</sub>>) and CT-defined volumes were extracted for abdominal and visceral organs, muscles, and adipose-tissue using automated image segmentation of baseline [<sup>18</sup>F]FDG-PET/CT images. Imaging and non-imaging parameters from laboratory tests were compared statistically. A machine-learning (ML) model was then trained to classify LCP as 'No CAC', 'Dev CAC', and 'CAC' based on their imaging parameters. SHapley Additive exPlanations (SHAP) analysis was employed to identify the key factors contributing to CAC development for each patient.</p><p><strong>Results: </strong>The three CAC categories displayed multi-organ differences in <SUV<sub>aorta</sub>>. In all target organs, <SUV<sub>aorta</sub>> was higher in the 'CAC' cohort compared with 'No CAC' (P < 0.01), except for liver and kidneys, where <SUV<sub>aorta</sub>> in 'CAC' was reduced by 5%. The 'Dev CAC' cohort displayed a small but significant increase in <SUV<sub>aorta</sub>> of pancreas (+4%), skeletal-muscle (+7%), subcutaneous adipose-tissue (+11%), and visceral adipose-tissue (+15%). In 'CAC' patients, a strong negative Spearman correlation (ρ = -0.8) was identified between <SUV<sub>aorta</sub>> and volumes of adipose-tissue. The machine-learning model identified 'CAC' at baseline with 81% of accuracy, highlighting <SUV<sub>aorta</sub>> of spleen, pancreas, liver, and adipose-tissue as most relevant features. The model performance was suboptimal (54%) when classifying 'Dev CAC' versus 'No CAC'.</p><p><strong>Conclusions: </strong>WB [<sup>18</sup>F]FDG-PET/CT imaging reveals groupwise differences in the multi-organ metabolism of LCP with and without CAC, thus highlighting systemic metabolic aberrations symptomatic of cachectic patients. Based on a retrospective cohort, our ML model identified patients ","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142071596","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Hans-Jonas Meyer, Tihomir Dermendzhiev, Michael Hetz, Georg Osterhoff, Christian Kleber, Timm Denecke, Jeanette Henkelmann, Robert Werdehausen, Gunther Hempel, Manuel F Struck
Background: Body composition parameters provide relevant prognostic significance in critical care cohorts and cancer populations. Published results regarding polytrauma patients are inconclusive to date. The goal of this study was to analyse the role of body composition parameters in severely injured trauma patients.
Methods: All consecutive patients requiring emergency tracheal intubation and mechanical ventilation before initial computed tomography (CT) at a level-1 trauma centre over a 12-year period (2008-2019) were reanalysed. The analysis included CT-derived body composition parameters based upon whole-body trauma CT as prognostic variables for 30-day mortality, intensive care unit length of stay (ICU LOS) and mechanical ventilation duration.
Results: Four hundred seventy-two patients (75% male) with a median age of 49 years, median injury severity score of 26 and 30-day mortality rate of 22% (104 patients) met the inclusion criteria and were analysed. Regarding body composition parameters, 231 patients (49%) had visceral obesity, 75 patients had sarcopenia (16%) and 35 patients had sarcopenic obesity (7.4%). After adjustment for statistically significant univariable predictors age, body mass index, sarcopenic obesity, visceral obesity, American Society of Anesthesiologists classification ≥3, injury severity score and Glasgow Coma Scale ≤ 8 points, the Cox proportional hazard model identified sarcopenia as significant prognostic factor of 30-day mortality (hazard ratio 2.84; 95% confidence interval 1.38-5.85; P = 0.004), which was confirmed in Kaplan-Meier survival analysis (log-rank P = 0.006). In a subanalysis of 363 survivors, linear multivariable regression analysis revealed no significant associations of body composition parameters with ICU LOS and duration of mechanical ventilation.
Conclusions: In a multivariable analysis of mechanically ventilated trauma patients, CT-defined sarcopenia was significantly associated with 30-day mortality whereas no associations of body composition parameters with ICU LOS and duration of mechanical ventilation were observed.
{"title":"Body composition parameters in initial CT imaging of mechanically ventilated trauma patients: Single-centre observational study.","authors":"Hans-Jonas Meyer, Tihomir Dermendzhiev, Michael Hetz, Georg Osterhoff, Christian Kleber, Timm Denecke, Jeanette Henkelmann, Robert Werdehausen, Gunther Hempel, Manuel F Struck","doi":"10.1002/jcsm.13578","DOIUrl":"https://doi.org/10.1002/jcsm.13578","url":null,"abstract":"<p><strong>Background: </strong>Body composition parameters provide relevant prognostic significance in critical care cohorts and cancer populations. Published results regarding polytrauma patients are inconclusive to date. The goal of this study was to analyse the role of body composition parameters in severely injured trauma patients.</p><p><strong>Methods: </strong>All consecutive patients requiring emergency tracheal intubation and mechanical ventilation before initial computed tomography (CT) at a level-1 trauma centre over a 12-year period (2008-2019) were reanalysed. The analysis included CT-derived body composition parameters based upon whole-body trauma CT as prognostic variables for 30-day mortality, intensive care unit length of stay (ICU LOS) and mechanical ventilation duration.</p><p><strong>Results: </strong>Four hundred seventy-two patients (75% male) with a median age of 49 years, median injury severity score of 26 and 30-day mortality rate of 22% (104 patients) met the inclusion criteria and were analysed. Regarding body composition parameters, 231 patients (49%) had visceral obesity, 75 patients had sarcopenia (16%) and 35 patients had sarcopenic obesity (7.4%). After adjustment for statistically significant univariable predictors age, body mass index, sarcopenic obesity, visceral obesity, American Society of Anesthesiologists classification ≥3, injury severity score and Glasgow Coma Scale ≤ 8 points, the Cox proportional hazard model identified sarcopenia as significant prognostic factor of 30-day mortality (hazard ratio 2.84; 95% confidence interval 1.38-5.85; P = 0.004), which was confirmed in Kaplan-Meier survival analysis (log-rank P = 0.006). In a subanalysis of 363 survivors, linear multivariable regression analysis revealed no significant associations of body composition parameters with ICU LOS and duration of mechanical ventilation.</p><p><strong>Conclusions: </strong>In a multivariable analysis of mechanically ventilated trauma patients, CT-defined sarcopenia was significantly associated with 30-day mortality whereas no associations of body composition parameters with ICU LOS and duration of mechanical ventilation were observed.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054380","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Leticia W Ribeiro, Sara Berndt, Gregore I Mielke, Jenny Doust, Gita D Mishra
Background: Muscle strength is essential for healthy ageing. Handgrip strength (HGS) has been recommended by expert bodies as the preferred measure of muscle strength, in addition to being considered a strong predictor of overall health. Cross-sectional studies have shown several potential factors associated with HGS, but a systematic review of factors predicting HGS over time has not previously been conducted. The aim of this study is to systematically review the literature on the factors associated with adult HGS [at follow-up(s) or its rate of change] across the life course.
Methods: Searches were performed in MEDLINE via Ebsco, Embase and SPORTDiscus databases. Longitudinal studies assessing potential factors impacting adult HGS over time were included in the analyses. Based on previously established definitions of consistency of results, a semiquantitative analysis was conducted using the proportions of studies supporting correlations with HGS.
Results: A total of 117 articles were included in this review. Factors associated with HGS were grouped into 11 domains: demographic, socioeconomic, genetic, early life, body composition, health markers/biomarkers, health conditions, psychosocial, lifestyle, reproductive and environmental determinants. Overall, 103 factors were identified, of which 10 showed consistent associations with HGS over time (i.e., in at least four studies with ≥60% agreement in the direction of association). Factors associated with greater declines in HGS included increasing age, male sex, higher levels of inflammatory markers and the presence of cardiovascular diseases. Education level, medication use, and self-rated health were not associated with the rate of change in HGS. Increased birth weight was associated with a stronger HGS over time, whereas depressive symptoms were linked to a weaker HGS, and smoking habits showed null associations.
Conclusions: Comparison between studies and estimation of effect sizes were limited due to the heterogeneity in methods. Although sex and age may be the main drivers of HGS decline, it is crucial to prioritize modifiable factors such as inflammation and cardiovascular diseases in health interventions to prevent greater losses. Interventions to improve birth weight and mental health are also likely to produce positive effects on muscle strength. Our results point to the complexity of processes involving muscle strength and suggest that the need to better understand the determinants of HGS remains.
{"title":"Factors associated with handgrip strength across the life course: A systematic review.","authors":"Leticia W Ribeiro, Sara Berndt, Gregore I Mielke, Jenny Doust, Gita D Mishra","doi":"10.1002/jcsm.13586","DOIUrl":"https://doi.org/10.1002/jcsm.13586","url":null,"abstract":"<p><strong>Background: </strong>Muscle strength is essential for healthy ageing. Handgrip strength (HGS) has been recommended by expert bodies as the preferred measure of muscle strength, in addition to being considered a strong predictor of overall health. Cross-sectional studies have shown several potential factors associated with HGS, but a systematic review of factors predicting HGS over time has not previously been conducted. The aim of this study is to systematically review the literature on the factors associated with adult HGS [at follow-up(s) or its rate of change] across the life course.</p><p><strong>Methods: </strong>Searches were performed in MEDLINE via Ebsco, Embase and SPORTDiscus databases. Longitudinal studies assessing potential factors impacting adult HGS over time were included in the analyses. Based on previously established definitions of consistency of results, a semiquantitative analysis was conducted using the proportions of studies supporting correlations with HGS.</p><p><strong>Results: </strong>A total of 117 articles were included in this review. Factors associated with HGS were grouped into 11 domains: demographic, socioeconomic, genetic, early life, body composition, health markers/biomarkers, health conditions, psychosocial, lifestyle, reproductive and environmental determinants. Overall, 103 factors were identified, of which 10 showed consistent associations with HGS over time (i.e., in at least four studies with ≥60% agreement in the direction of association). Factors associated with greater declines in HGS included increasing age, male sex, higher levels of inflammatory markers and the presence of cardiovascular diseases. Education level, medication use, and self-rated health were not associated with the rate of change in HGS. Increased birth weight was associated with a stronger HGS over time, whereas depressive symptoms were linked to a weaker HGS, and smoking habits showed null associations.</p><p><strong>Conclusions: </strong>Comparison between studies and estimation of effect sizes were limited due to the heterogeneity in methods. Although sex and age may be the main drivers of HGS decline, it is crucial to prioritize modifiable factors such as inflammation and cardiovascular diseases in health interventions to prevent greater losses. Interventions to improve birth weight and mental health are also likely to produce positive effects on muscle strength. Our results point to the complexity of processes involving muscle strength and suggest that the need to better understand the determinants of HGS remains.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054382","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Edward J Hardy, Joseph J Bass, Thomas B Inns, Mathew Piasecki, Jessica Piasecki, Craig Sale, Robert H Morris, Jonathan N Lund, Ken Smith, Daniel J Wilkinson, Philip J Atherton, Bethan E Phillips
Background: Skeletal muscle is a highly plastic tissue crucial for many functions associated with whole-body health across the life course. Magnetic resonance imaging (MRI) is the current gold standard for measuring skeletal muscle size. However, MRI is expensive, and access to facilities is often limited. B-mode ultrasonography (U/S) has been proposed as a potential alternative to MRI for the assessment of muscle size. However, to date, no work has explored the utility of U/S to assess disuse muscle atrophy (DMA) across muscles with different atrophy susceptibility profiles, an omission which may limit the clinical application of previous work.
Methods: To address this significant knowledge gap, 10 young men (22 ± years, 24.1 ± 2.3 kg/m2) underwent 15-day unilateral leg immobilization using a knee-brace and air boot. Cross-sectional area (CSA) and muscle thickness (MT) of the tibialis anterior (TA) and medial gastrocnemius (MG) were assessed via U/S before and after immobilization, with CSA and muscle volume assessed via MRI.
Results: With both muscles combined, there were good correlations between each U/S and MRI measure, both before (e.g., CSAMRI vs. MTU/S and CSAU/S: r = 0.88 and 0.94, respectively, both P < 0.0001) and after (e.g., VOLMRI vs. MTU/S and CSAU/S: r = 0.90 and 0.96, respectively, both P < 0.0001) immobilization. The relationship between the methods was notably stronger for MG than TA at each time-point (e.g., CSAMRI vs. MTU/S: MG, r = 0.70, P = 0.0006; TA, r = 0.37, P = 0.10). There was no relationship between the degree of DMA determined by the two methods in either muscle (e.g., TA pre- vs. post-immobilization, VOLMRI: 136 ± 6 vs. 133 ± 5, P = 0.08; CSAU/S: 6.05 ± 0.3 vs. 5.92 ± 0.4, P = 0.70; relationship between methods: r = 0.12, P = 0.75).
Conclusions: Both MTU/S and CSAU/S provide comparable static measures of lower leg muscle size compared with MRI, albeit with weaker agreement in TA compared to MG. Although both MTU/S and CSAU/S can discern differences in DMA susceptibility between muscles, neither can reliably assess degree of DMA. Based on the growing recognition of heterogeneous atrophy profiles between muscles, and the topical importance of less commonly studied muscles (i.e., TA for falls prevention in older adults), future research should aim to optimize accessible methods to determine muscle losses across the body.
{"title":"Exploring the utility of ultrasound to assess disuse atrophy in different muscles of the lower leg.","authors":"Edward J Hardy, Joseph J Bass, Thomas B Inns, Mathew Piasecki, Jessica Piasecki, Craig Sale, Robert H Morris, Jonathan N Lund, Ken Smith, Daniel J Wilkinson, Philip J Atherton, Bethan E Phillips","doi":"10.1002/jcsm.13583","DOIUrl":"https://doi.org/10.1002/jcsm.13583","url":null,"abstract":"<p><strong>Background: </strong>Skeletal muscle is a highly plastic tissue crucial for many functions associated with whole-body health across the life course. Magnetic resonance imaging (MRI) is the current gold standard for measuring skeletal muscle size. However, MRI is expensive, and access to facilities is often limited. B-mode ultrasonography (U/S) has been proposed as a potential alternative to MRI for the assessment of muscle size. However, to date, no work has explored the utility of U/S to assess disuse muscle atrophy (DMA) across muscles with different atrophy susceptibility profiles, an omission which may limit the clinical application of previous work.</p><p><strong>Methods: </strong>To address this significant knowledge gap, 10 young men (22 ± years, 24.1 ± 2.3 kg/m<sup>2</sup>) underwent 15-day unilateral leg immobilization using a knee-brace and air boot. Cross-sectional area (CSA) and muscle thickness (MT) of the tibialis anterior (TA) and medial gastrocnemius (MG) were assessed via U/S before and after immobilization, with CSA and muscle volume assessed via MRI.</p><p><strong>Results: </strong>With both muscles combined, there were good correlations between each U/S and MRI measure, both before (e.g., CSA<sub>MRI</sub> vs. MT<sub>U/S</sub> and CSA<sub>U/S</sub>: r = 0.88 and 0.94, respectively, both P < 0.0001) and after (e.g., VOL<sub>MRI</sub> vs. MT<sub>U/S</sub> and CSA<sub>U/S</sub>: r = 0.90 and 0.96, respectively, both P < 0.0001) immobilization. The relationship between the methods was notably stronger for MG than TA at each time-point (e.g., CSA<sub>MRI</sub> vs. MT<sub>U/S</sub>: MG, r = 0.70, P = 0.0006; TA, r = 0.37, P = 0.10). There was no relationship between the degree of DMA determined by the two methods in either muscle (e.g., TA pre- vs. post-immobilization, VOL<sub>MRI</sub>: 136 ± 6 vs. 133 ± 5, P = 0.08; CSA<sub>U/S</sub>: 6.05 ± 0.3 vs. 5.92 ± 0.4, P = 0.70; relationship between methods: r = 0.12, P = 0.75).</p><p><strong>Conclusions: </strong>Both MT<sub>U/S</sub> and CSA<sub>U/S</sub> provide comparable static measures of lower leg muscle size compared with MRI, albeit with weaker agreement in TA compared to MG. Although both MT<sub>U/S</sub> and CSA<sub>U/S</sub> can discern differences in DMA susceptibility between muscles, neither can reliably assess degree of DMA. Based on the growing recognition of heterogeneous atrophy profiles between muscles, and the topical importance of less commonly studied muscles (i.e., TA for falls prevention in older adults), future research should aim to optimize accessible methods to determine muscle losses across the body.</p>","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142054381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pamela N. Klassen, Vera C. Mazurak, Jessica Thorlakson, Stephane Servais
Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta‐analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative‐intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta‐analysis. Studies that measured computed tomography‐defined SM and/or AT change in adult patients during palliative‐intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2/m2, cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex‐specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta‐analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.
{"title":"Call for standardization in assessment and reporting of muscle and adipose change using computed tomography analysis in oncology: A scoping review","authors":"Pamela N. Klassen, Vera C. Mazurak, Jessica Thorlakson, Stephane Servais","doi":"10.1002/jcsm.13318","DOIUrl":"10.1002/jcsm.13318","url":null,"abstract":"Investigators are increasingly measuring skeletal muscle (SM) and adipose tissue (AT) change during cancer treatment to understand impact on patient outcomes. Recent meta‐analyses have reported high heterogeneity in this literature, representing uncertainty in the resulting estimates. Using the setting of palliative‐intent chemotherapy as an exemplar, we aimed to systematically summarize the sources of variability among studies evaluating SM and AT change during cancer treatment and propose standards for future studies to enable reliable meta‐analysis. Studies that measured computed tomography‐defined SM and/or AT change in adult patients during palliative‐intent chemotherapy for solid tumours were included, with no date or geographical limiters. Of 2496 publications screened by abstract/title, 83 were reviewed in full text and 38 included for extraction, representing 34 unique cohorts across 8 tumour sites. The timing of baseline measurement was frequently defined as prior to treatment, while endpoint timing ranged from 6 weeks after treatment start to time of progression. Fewer than 50% specified the actual time interval between measurements. Measurement error was infrequently discussed (8/34). A single metric (cm2/m2, cm2 or %) was used to describe SM change in 18/34 cohorts, while multiple metrics were presented for 10/34 and no descriptive metrics for 6/34. AT change metrics and sex‐specific reporting were available for 10/34 cohorts. Associations between SM loss and overall survival were evaluated in 24 publications, with classification of SM loss ranging from any loss to >14% loss over variable time intervals. Age and sex were the most common covariates, with disease response in 50% of models. Despite a wealth of data and effort, heterogeneity in study design, reporting and statistical analysis hinders evidence synthesis regarding the severity and outcomes of SM and AT change during cancer treatment. Proposed standards for study design include selection of homogenous cohorts, clear definition of baseline/endpoint timing and attention to measurement error. Standard reporting should include baseline SM and AT by sex, actual scan interval, SM and AT change using multiple metrics and visualization of the range of change observed. Reporting by sex would advance understanding of sexual dimorphism in SM and AT change. Evaluating the impact of tissue change on outcomes requires adjustment for relevant covariates and concurrent disease response. Adoption of these standards by researchers and publishers would alter the current paradigm to enable meta‐analysis of future studies and move the field towards meaningful application of SM and AT change to clinical care.","PeriodicalId":186,"journal":{"name":"Journal of Cachexia, Sarcopenia and Muscle","volume":null,"pages":null},"PeriodicalIF":8.9,"publicationDate":"2023-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jcsm.13318","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10524503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}