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  • 1
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 12, No. 6 ( 2021-12), p. 1418-1427
    Abstract: Although growth differentiation factor 15 (GDF15) is known to increase with disease and is associated with low physical performance, the role of GDF15 in normal ageing is still not fully understood. Specifically, the influence of circulating GDF15 on impairments in maximal muscle power (a major contributor to functional limitations) and the underlying components has not been investigated. Methods Data from 1305 healthy women and men aged 20 to 93 years from The Copenhagen Sarcopenia Study were analysed. Circulating levels of GDF15 and markers of inflammation (tumor necrosis factor‐alpha, interleukin‐6, and high‐sensitivity C‐reactive protein) were measured by ELISA (R & D Systems) and multiplex bead‐based immunoassays (Bio‐Rad). Relative (normalized to body mass), allometric (normalized to height squared), and specific (normalized to leg muscle mass) muscle power were assessed by the Nottingham power rig [leg extension power (LEP)] and the 30 s sit‐to‐stand (STS) muscle power test. Total body fat, visceral fat, and leg lean mass were assessed by dual energy X‐ray absorptiometry. Leg skeletal muscle index was measured as leg lean mass normalized to body height squared. Results Systemic levels of GDF15 increased progressively as a function of age in women (1.1 ± 0.4 pg·mL −1 ·year −1 ) and men (3.3 ± 0.6 pg·mL −1 ·year −1 ) (both P   〈  0.05). Notably, GDF15 increased at a faster rate from the age of 65 years in women (11.5 ± 1.2 pg·mL −1 ·year −1 , P   〈  0.05) and 70 years in men (19.3 ± 2.3 pg·mL −1 ·year −1 , P   〈  0.05), resulting in higher GDF15 levels in men compared with women above the age of 65 years ( P   〈  0.05). Independently of age and circulatory markers of inflammation, GDF15 was negatively correlated to relative STS power ( P   〈  0.05) but not LEP, in both women and men. These findings were mainly explained by negative associations of GDF15 with specific STS power in women and men (both P   〈  0.05). Conclusions A J‐shaped relationship between age and systemic GDF15 was observed, with men at older age showing steeper increases and elevated GDF15 levels compared with women. Importantly, circulating GDF15 was independently and negatively associated with relative STS power, supporting the potential role of GDF15 as a sensitive biomarker of frailty in older people.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2586864-0
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  • 2
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 10, No. 1 ( 2020-10-01)
    Abstract: This study aimed to assess the validity and functional relevance of a standardized procedure to assess lower limb muscle power by means of the 30-s sit-to-stand (STS) test when compared to leg extension power (LEP), traditional STS performance and handgrip strength. A total of 628 community-dwelling older subjects (60–93 years) from the Copenhagen Sarcopenia Study were included. Physical performance was assessed by the 30-s STS and 10-m maximal gait speed tests. Handgrip strength and LEP were recorded by a hand-held dynamometer and the Nottingham power rig, respectively. STS muscle power was calculated using the subjects’ body mass and height, chair height and the number of repetitions completed in the 30-s STS test. We found a small albeit significant difference between LEP and unilateral STS power in older men (245.5 ± 88.8 vs. 223.4 ± 81.4 W; ES = 0.26; p   〈  0.05), but not in older women (135.9 ± 51.9 vs. 138.5 ± 49.6 W; ES = 0.05; p   〉  0.05). Notably, a large positive correlation was observed between both measures (r = 0.75; p   〈  0.001). Relative STS power was more strongly related with maximal gait speed than handgrip strength, repetition-based STS performance and relative LEP after adjusting for age (r = 0.53 vs 0.35–0.45; p   〈  0.05). In conclusion, STS power obtained from the 30-s STS test appeared to provide a valid measure of bilateral lower limb power and was more strongly related with physical performance than maximal handgrip strength, repetition-based STS performance and LEP.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
    detail.hit.zdb_id: 2615211-3
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  • 3
    In: Experimental Gerontology, Elsevier BV, Vol. 152 ( 2021-09), p. 111448-
    Type of Medium: Online Resource
    ISSN: 0531-5565
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2021
    detail.hit.zdb_id: 2005397-6
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  • 4
    In: Journal of Cachexia, Sarcopenia and Muscle, Wiley, Vol. 12, No. 6 ( 2021-12), p. 1641-1652
    Abstract: Chronic low‐grade inflammation has been suggested as one of the key elements in the development of sarcopenia, but in contrast to disease‐related loss of muscle mass, the role of chronic low‐grade inflammation in age‐related (primary) sarcopenia is still not clear. The aim of this study was to investigate low‐grade inflammation in relation to age and the potential association between inflammatory biomarkers and body composition, muscle strength and physical performance in a healthy Danish cohort. Methods There were 1160 generally healthy men and women (range: 22–93 years) included. Appendicular lean mass (ALM) and visceral fat normalized to height (kg/m 2 ) was assessed by dual‐energy X‐ray absorptiometry (iDXA, GE Lunar). Muscle strength and physical performance were evaluated by handgrip strength (HGS), 30 s sit‐to‐stand performance, and maximal gait speed (GS). Systemic levels of TNF‐α, IL‐6, IL‐1β, IL‐4, IL‐13, and IFN‐γ were measured using multiplex bead‐based immunoassays (Bio‐Rad). hsCRP was assessed using latex particle‐enhanced immunoturbidimetric assays (Roche Diagnostics). Results With age, ALM/h 2 , HGS, sit‐to‐stand performance and GS decreased, whereas visceral fat/h 2 increased in both men and women ( P   〈  0.05). Systemic levels of hsCRP, TNF‐α, IL‐4, and IFN‐γ increased with age in men and women ( P   〈  0.05), while IL‐1β increased in women only ( P   〈  0.01). Higher levels of hsCRP were associated with lower ALM/h 2 in elderly (≥65 years) men and women ( P   〈  0.001). Higher levels of hsCRP were associated with lower handgrip strength in elderly women ( P   〈  0.05) whereas higher levels of hsCRP was not associated with lower HGS in elderly men ( P  = 0.056). Higher levels of hsCRP were associated with lower GS ( P   〈  0.05), whereas IFN‐γ was positively associated with GS in elderly women ( P   〈  0.05), but not elderly men. Visceral fat index was positively associated with hsCRP in elderly men and women ( P   〈  0.001). Compared with elderly with normal HGS, elderly men and women with low HGS displayed higher levels of TNF‐α and hsCRP ( P   〈  0.05). Conclusions With age, systemic levels of hsCRP, TNF‐α, IL‐4, and IFN‐γ increased, with hsCRP and TNF‐α being especially elevated in more physically frail elderly supporting the association between low‐grade systemic inflammation and poor physical function. In contrast, only high levels of hsCRP were weakly associated with low muscle mass and positively associated with visceral fat and low physical function, suggesting that chronic low‐grade inflammation is not the main driver of age‐related loss of muscle mass as previously suggested.
    Type of Medium: Online Resource
    ISSN: 2190-5991 , 2190-6009
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2021
    detail.hit.zdb_id: 2586864-0
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  • 5
    In: BMJ Open, BMJ, Vol. 10, No. 12 ( 2020-12), p. e042786-
    Abstract: Sarcopenia is generally used to describe the age-related loss of muscle mass and strength believed to play a major role in the pathogenesis of physical frailty and functional impairment that may occur with old age. The knowledge surrounding the prevalence and determinants of sarcopenia in older medical patients is scarce, and it is unknown whether specific biomarkers can predict physical deconditioning during hospitalisation. We hypothesise that a combination of clinical, functional and circulating biomarkers can serve as a risk stratification tool and can (i) identify older acutely ill medical patients at risk of prolonged hospital stays and (ii) predict changes in muscle mass, muscle strength and function during hospitalisation. Method and analysis The Copenhagen PROTECT study is a prospective cohort study consisting of acutely ill older medical patients admitted to the acute medical ward at Copenhagen University Hospital, Bispebjerg and Frederiksberg, Denmark. Assessments are performed within 24 hours of admission and include blood samples, body composition, muscle strength, physical function and questionnaires. A subgroup of patients transferred to the Geriatric Department are included in a smaller geriatric cohort and have additional assessments at discharge to evaluate the relative change in circulating biomarker concentrations, body composition, muscle strength and physical function during hospitalisation. Enrolment commenced 4 November 2019, and proceeds until August 2021. Ethics and dissemination The study protocol has been approved by the local ethics committee of Copenhagen and Frederiksberg (H-19039214) and the Danish Data Protection Agency (P-2019-239) and all experimental procedures were performed in accordance with the Declaration of Helsinki. Findings from the project, regardless of the outcome, will be published in relevant peer-reviewed scientific journals in online ( www.clinicaltrials.gov ). Trial registration number NCT04151108
    Type of Medium: Online Resource
    ISSN: 2044-6055 , 2044-6055
    Language: English
    Publisher: BMJ
    Publication Date: 2020
    detail.hit.zdb_id: 2599832-8
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  The Journals of Gerontology: Series A Vol. 75, No. 7 ( 2020-06-18), p. 1369-1378
    In: The Journals of Gerontology: Series A, Oxford University Press (OUP), Vol. 75, No. 7 ( 2020-06-18), p. 1369-1378
    Abstract: Our main goal was to evaluate the pattern and time course of changes in relative muscle power and its constituting components throughout the life span. Methods A total of 1,305 subjects (729 women and 576 men; aged 20–93 years) participating in the Copenhagen Sarcopenia Study took part. Body mass index (BMI), leg lean mass assessed by dual-energy X-ray absorptiometry (DXA), and leg extension muscle power (LEP) assessed by the Nottingham power rig were recorded. Relative muscle power (normalized to body mass) and specific muscle power (normalized to leg lean mass) were calculated. Segmented regression analyses were used to identify the onset and pattern of age-related changes in the recorded variables. Results Relative muscle power began to decline above the age of 40 in both women and men, with women showing an attenuation of the decline above 75 years. Relative muscle power decreased with age due to (i) the loss of absolute LEP after the fourth decade of life and (ii) the increase in BMI up to the age of 75 years in women and 65 years in men. The decline in absolute LEP was caused by a decline in specific LEP up to the age of 75 in women and 65 in men, above which the loss in relative leg lean mass also contributed. Conclusions Relative power decreased (i) above 40 years by the loss in absolute power (specific power only) and the increase in body mass, and (ii) above ~70 years by the loss in absolute power (both specific power and leg lean mass).
    Type of Medium: Online Resource
    ISSN: 1079-5006 , 1758-535X
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
    detail.hit.zdb_id: 2043927-1
    SSG: 12
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  • 7
    In: Journal of the American Medical Directors Association, Elsevier BV, Vol. 24, No. 12 ( 2023-12), p. 1898-1903
    Type of Medium: Online Resource
    ISSN: 1525-8610
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
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  • 8
    In: European Journal of Haematology, Wiley, Vol. 96, No. 3 ( 2016-03), p. 252-259
    Abstract: The tumour microenvironment in classical Hodgkin's lymphoma ( cHL ) is characterised by a minor population of neoplastic Hodgkin and Reed–Sternberg cells within a heterogeneous background of non‐neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour‐infiltrating mast cells in cHL tissue microarrays and correlated this with clinico‐pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis ( NS ) subtype histology ( P  = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD 68+ and CD 163+ macrophages ( P  = 0.0001 and P  = 0.003, respectively) and with the number of granzyme+ cytotoxic cells ( P  = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall ( P  = 0.03) and event‐free survival ( P  = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.
    Type of Medium: Online Resource
    ISSN: 0902-4441 , 1600-0609
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2016
    detail.hit.zdb_id: 2027114-1
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