Browsing by Subject "SARCOPENIA"

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  • Mikkola, Tuija M; Salonen, Minna K; Kajantie, Eero; Kautiainen, Hannu; Eriksson, Johan G (2020)
    Circulating amino acids are potential markers of body composition. Previous studies are mainly limited to middle age and focus on either fat or lean mass, thereby ignoring overall body composition. We investigated the associations of fat and lean body mass with circulating amino acids in older men and women. We studied 594 women and 476 men from the Helsinki Birth Cohort Study (age 62–74 years). Bioelectrical impedance analysis was used to indicate two main body compartments by fat (fat mass/height2) and lean mass indices (lean mass/height2), dichotomized based on sex-specific medians. Eight serum amino acids were quantified using nuclear magnetic resonance spectroscopy. General linear models were adjusted for age, smoking, and fasting glucose. Higher lean mass index (LMI) was associated with higher concentrations of branched-chain amino acids in both sexes (p ≤ .001). In men, LMI was also positively associated with tyrosine (p = .006) and inversely with glycine (p < .001). Higher fat mass index was associated with higher concentrations of all branched-chain amino acids, aromatic amino acids (phenylalanine and tyrosine), and alanine in both sexes (p ≤ .008). Associations between body composition and amino acids are largely similar in older men and women. The associations are largely similar to those previously observed in younger adults.
  • Paajanen, Juuso; Ilonen, Ilkka; Lauri, Helena; Järvinen, Tommi; Sutinen, Eva; Ollila, Hely; Rouvinen, Eeva; Lemström, Karl; Räsänen, Jari; Ritvos, Olli; Koli, Katri; Myllärniemi, Marjukka (2020)
    Activin A has previously been associated with cancer cachexia and in vitro resistance to platinum-based chemotherapy. We studied circulating activin A concentrations as well as activin B and their antagonists' follistatin/follistatin-like 3 in presurgical patients with non-small-cell lung cancer and malignant pleural mesothelioma. We found that circulating activing A levels were elevated in malignant pleural mesothelioma and associated with cancer cachexia and poor response to platinum-based chemotherapy. Circulating activing A separated non-small-cell lung cancer from benign lung lesion. Background: Previous preclinical studies have shown that activin A is overexpressed in malignant pleural mesothelioma (MPM), associates with cancer cachexia, and is observed in in vitro resistance to platinum-based chemotherapy. We evaluated circulating activin levels and their endogenous antagonists' follistatin/follistatin-like 3 in intrathoracic tumors. Materials and Methods: Patients suspected of thoracic malignancy were recruited prior to surgery. Serum samples were collected from 21 patients with MPM, 59 patients with non-small-cell lung cancer (NSCLC), and 22 patients with benign lung lesions. Circulating activin/follistatin levels were measured using enzymelinked immunosorbent assay and compared with clinicopathologic parameters. Results: Circulating activin A levels were elevated in patients with MPM when compared with patients with NSCLC or benign lung lesion samples (P <.0001). Also, follistatin and follistatin-like 3 levels were the highest in MPM, although with less difference compared with activin A. Receiver operating characteristic analysis for activin A for separating NSCLC from benign lung lesion showed an area under the curve of 0.856 (95% confidence interval, 0.77-0.94). Activin A levels were higher in patients with cachexia (P <.001). In patients with MPM, activin A levels correlated positively with computed tomographybased baseline tumor size (R = 0.549; P = .010) and the change in tumor size after chemotherapy (R = 0.743; P = .0006). Patients with partial response or stable disease had lower circulating activin A levels than the ones with progressive disease (P = .028). Conclusion: Activin A serum level could be used as a biomarker in differentiating malignant and benign lung tumors. Circulating activin A levels were elevated in MPM and associates with cancer cachexia and reduced chemotherapy response. (C) 2019 The Author(s). Published by Elsevier Inc.
  • Zillikens, M. Carola; Demissie, Serkalem; Hsu, Yi-Hsiang; Yerges-Armstrong, Laura M.; Chou, Wen-Chi; Stolk, Lisette; Livshits, Gregory; Broer, Linda; Johnson, Toby; Koller, Daniel L.; Kutalik, Zoltyn; Luan, Jian'an; Malkin, Ida; Ried, Janina S.; Smith, Albert V.; Thorleifsson, Gudmar; Vandenput, Liesbeth; Zhao, Jing Hua; Zhang, Weihua; Aghdassi, Ali; Akesson, Kristina; Amin, Najaf; Baier, Leslie J.; Barroso, Ines; Bennett, David A.; Bertram, Lars; Biffar, Rainer; Bochud, Murielle; Boehnke, Michael; Borecki, Ingrid B.; Buchman, Aron S.; Byberg, Liisa; Campbell, Harry; Obanda, Natalia Campos; Cauley, Jane A.; Cawthon, Peggy M.; Cederberg, Henna; Chen, Zhao; Cho, Nam H.; Choi, Hyung Jin; Claussnitzer, Melina; Collins, Francis; Cummings, Steven R.; De Jager, Philip L.; Demuth, Ilja; Dhonukshe-Rutten, Rosalie A. M.; Diatchenko, Luda; Eiriksdottir, Gudny; Enneman, Anke W.; Erdos, Mike; Eriksson, Johan G.; Eriksson, Joel; Estrada, Karol; Evans, Daniel S.; Feitosa, Mary F.; Fu, Mao; Garcia, Melissa; Gieger, Christian; Girke, Thomas; Glazer, Nicole L.; Grallert, Harald; Grewal, Jagvir; Han, Bok-Ghee; Hanson, Robert L.; Hayward, Caroline; Hofman, Albert; Hoffman, Eric P.; Homuth, Georg; Hsueh, Wen-Chi; Hubal, Monica J.; Hubbard, Alan; Huffman, Kim M.; Husted, Lise B.; Illig, Thomas; Ingelsson, Erik; Ittermann, Till; Jansson, John-Olov; Jordan, Joanne M.; Jula, Antti; Karlsson, Magnus; Khaw, Kay-Tee; Kilpainen, Tuomas O.; Klopp, Norman; Kloth, Jacqueline S. L.; Koistinen, Heikki A.; Kraus, William E.; Kritchevsky, Stephen; Kuulasmaa, Teemu; Kuusisto, Johanna; Laakso, Markku; Lahti, Jari; Lang, Thomas; Langdahl, Bente L.; Launer, Lenore J.; Lee, Jong-Young; Lerch, Markus M.; Lewis, Joshua R.; Lind, Lars; Lindgren, Cecilia; Liu, Yongmei; Liu, Tian; Liu, Youfang; Ljunggren, Osten; Lorentzon, Mattias; Luben, Robert N.; Maixner, William; McGuigan, Fiona E.; Medina-Gomez, Carolina; Meitinger, Thomas; Melhus, Hakan; Mellstrom, Dan; Melov, Simon; Michaelsson, Karl; Mitchell, Braxton D.; Morris, Andrew P.; Mosekilde, Leif; Newman, Anne; Nielson, Carrie M.; O'Connell, Jeffrey R.; Oostra, Ben A.; Orwoll, Eric S.; Palotie, Aarno; Parker, Stephen C. J.; Peacock, Munro; Perola, Markus; Peters, Annette; Polasek, Ozren; Prince, Richard L.; Raikkonen, Katri; Ralston, Stuart H.; Ripatti, Samuli; Robbins, John A.; Rotter, Jerome I.; Rudan, Igor; Salomaa, Veikko; Satterfield, Suzanne; Schadt, Eric E.; Schipf, Sabine; Scott, Laura; Sehmi, Joban; Shen, Jian; Shin, Chan Soo; Sigurdsson, Gunnar; Smith, Shad; Soranzo, Nicole; Stancakova, Alena; Steinhagen-Thiessen, Elisabeth; Streeten, Elizabeth A.; Styrkarsdottir, Unnur; Swart, Karin M. A.; Tan, Sian-Tsung; Tarnopolsky, Mark A.; Thompson, Patricia; Thomson, Cynthia A.; Thorsteinsdottir, Unnur; Tikkanen, Emmi; Tranah, Gregory J.; Tuomilehto, Jaakko; van Schoor, Natasja M.; Verma, Arjun; Vollenweider, Peter; Voelzke, Henry; Wactawski-Wende, Jean; Walker, Mark; Weedon, Michael N.; Welch, Ryan; Wichmann, H. -Erich; Widen, Elisabeth; Williams, Frances M. K.; Wilson, James F.; Wright, Nicole C.; Xie, Weijia; Yu, Lei; Zhou, Yanhua; Chambers, John C.; Doring, Angela; van Duijn, Cornelia M.; Econs, Michael J.; Gudnason, Vilmundur; Kooner, Jaspal S.; Psaty, Bruce M.; Spector, Timothy D.; Stefansson, Kari; Rivadeneira, Fernando; Uitterlinden, Andre G.; Wareham, Nicholas J.; Ossowski, Vicky; Waterworth, Dawn; Loos, Ruth J. F.; Karasik, David; Harris, Tamara B.; Ohlsson, Claes; Kiel, Douglas P. (2017)
    Lean body mass, consisting mostly of skeletal muscle, is important for healthy aging. We performed a genome-wide association study for whole body (20 cohorts of European ancestry with n = 38,292) and appendicular (arms and legs) lean body mass (n = 28,330) measured using dual energy X-ray absorptiometry or bioelectrical impedance analysis, adjusted for sex, age, height, and fat mass. Twenty-one single-nucleotide polymorphisms were significantly associated with lean body mass either genome wide (p <5 x 10(-8)) or suggestively genome wide (p <2.3 x 10(-6)). Replication in 63,475 (47,227 of European ancestry) individuals from 33 cohorts for whole body lean body mass and in 45,090 (42,360 of European ancestry) subjects from 25 cohorts for appendicular lean body mass was successful for five single-nucleotide polymorphisms in/ near HSD17B11, VCAN, ADAMTSL3, IRS1, and FTO for total lean body mass and for three single-nucleotide polymorphisms in/ near VCAN, ADAMTSL3, and IRS1 for appendicular lean body mass. Our findings provide new insight into the genetics of lean body mass.
  • Järvinen, Tommi; Ilonen, Ilkka; Kauppi, Juha; Salo, Jarmo; Räsänen, Jari (2018)
    Background: Nutritional deficits, cachexia, and sarcopenia are extremely common in esophageal cancer. The aim of this article was to assess the effect of loss of skeletal muscle mass during neoadjuvant treatment on the prognosis of esophageal cancer patients. Methods: Esophageal cancer patients (N = 115) undergoing neoadjuvant therapy and surgery between 2010 and 2014 were identified from our surgery database and retrospectively analyzed. Computed tomography imaging of the total cross-sectional muscle tissue measured at the third lumbar level defined the skeletal muscle index, which defined sarcopenia (SMI <52.4 cm2/m2 for men and <38.5 cm2/m2 for women). Images were collected before and after neoadjuvant treatments. Results: Sarcopenia in preoperative imaging was prevalent in 92 patients (80%). Median overall survival was 900 days (interquartile range 334-1447) with no difference between sarcopenic (median = 900) and non-sarcopenic (median = 914) groups (p = 0.872). Complication rates did not differ (26.1% vs 32.6%, p = 0.725). A 2.98% decrease in skeletal muscle index during neoadjuvant treatment correlated with poor 2-year survival (log-rank p = 0.04). Conclusion: Loss of skeletal muscle tissue during neoadjuvant treatment correlates with worse overall survival.
  • Järvinen, Tommi; Ilonen, Ilkka; Kauppi, Juha; Volmonen, Kirsi; Salo, Jarmo; Räsänen, Jari (2018)
    Background Methods In esophageal cancer, nutritional challenges are extremely common. Malignant obstruction resulting from esophageal cancer (EC) is often treated by the insertion of expandable stents, but little is known as to the role and evolution of sarcopenia in this patient population. The aim of this article was to determine the effects of body mass parameters on survival of advanced EC patients who received a stent for palliation of malignant obstruction. This was a retrospective observational study of 238 EC patients who had a stent inserted for palliation of malignant obstruction between 2005 and 2013. Skeletal muscle mass was calculated from abdominal computed tomography scans, and the patients were divided into sarcopenic and non-sarcopenic groups. A follow-up computed tomography scan was available in 118 patients. The primary outcome was survival, and complication rates and the need for an alternative enteral feeding route were secondary outcomes. Results Conclusions Sarcopenia occurred in 199 (85%) patients. Median survival was 146 (range: 76-226) days in the sarcopenia group and 152 (range: 71-249) days in the non-sarcopenic group (P = 0.61). Complication rates between the groups were not significantly different (P = 0.85). In Cox regression analysis, the skeletal muscle index was inversely correlated with overall survival (hazard ratio 0.98, 95% confidence interval 0.97-0.99; P = 0.033). Sarcopenia, defined by consensus thresholds, at the time of stent insertion cannot effectively predict poor survival in this patient cohort, but a lower skeletal muscle index correlates with poor prognosis as a continuous variable.
  • SPRINTT Consortium (2022)
    OBJECTIVE To determine whether a multicomponent intervention based on physical activity with technological support and nutritional counselling prevents mobility disability in older adults with physical frailty and sarcopenia. DESIGN Evaluator blinded, randomised controlled trial. SETTING 16 clinical sites across 11 European countries, January 2016 to 31 October 2019. PARTICIPANTS 1519 community dwelling men and women aged 70 years or older with physical frailty and sarcopenia, operationalised as the co-occurrence of low functional status, defined as a short physical performance battery (SPPB) score of 3 to 9, low appendicular lean mass, and ability to independently walk 400 m. 760 participants were randomised to a multicomponent intervention and 759 received education on healthy ageing (controls). INTERVENTIONS The multicomponent intervention comprised moderate intensity physical activity twice weekly at a centre and up to four times weekly at home. Actimetry data were used to tailor the intervention. Participants also received personalised nutritional counselling. Control participants received education on healthy ageing once a month. Interventions and follow-up lasted for up to 36 months. MAIN OUTCOME MEASURES The primary outcome was mobility disability (inability to independently walk 400 m in Physical frailty and sarcopenia may be targeted to preserve mobility in vulnerable older people. TRIAL REGISTRATION NCT02582138.
  • Solagna, Francesca; Tezze, C.; Lindenmeyer, M.T.; Lu, S.; Wu, G.; Liu, S.; Zhao, Y.; Mitchell, R.; Meyer, C.; Omairi, S.; Kilic, T.; Paolini, A.; Ritvos, O.; Pasternack, A.; Matsakas, A.; Kylies, D.; zur Wiesch, J.S.; Turner, J.-E.; Wanner, N.; Nair, V.; Eichinger, F.; Menon, R.; Martin, I.V.; Klinkhammer, B.M.; Hoxha, E.; Cohen, C.D.; Tharaux, P.-L.; Boor, P.; Ostendorf, T.; Kretzler, M.; Sandri, M.; Kretz, O.; Puelles, V.G.; Patel, K.; Huber, T.B. (2021)
    Skeletal muscle wasting is commonly associated with chronic kidney disease (CKD), resulting in increased morbidity and mortality. However, the link between kidney and muscle function remains poorly understood. Here, we took a complementary interorgan approach to investigate skeletal muscle wasting in CKD. We identified increased production and elevated blood levels of soluble pro-cachectic factors, including activin A, directly linking experimental and human CKD to skeletal muscle wasting programs. Single-cell sequencing data identified the expression of activin A in specific kidney cell populations of fibroblasts and cells of the juxtaglomerular apparatus. We propose that persistent and increased kidney production of procachectic factors, combined with a lack of kidney clearance, facilitates a vicious kidney/muscle signaling cycle, leading to exacerbated blood accumulation and, thereby, skeletal muscle wasting. Systemic pharmacological blockade of activin A using soluble activin receptor type IIB ligand trap as well as muscle-specific adeno-associated virus-mediated downregulation of its receptor ACVR2A/B prevented muscle wasting in different mouse models of experimental CKD, suggesting that activin A is a key factor in CKD-induced cachexia. In summary, we uncovered a crosstalk between kidney and muscle and propose modulation of activin signaling as a potential therapeutic strategy for skeletal muscle wasting in CKD.
  • THE EUROPEAN WORKING GROUP ON SARCOPENIA IN OLDER PEOPLE 2 (EWGSOP2); THE EXTENDED GROUP FOR EWGSOP2; Cruz-Jentoft, Alfonso J.; Bahat, Gülistan; Bauer, Jürgen; Boirie, Yves; Bruyere, Olivier; Cederholm, Tommy; Cooper, C.; Landi, Francesco; Rolland, Yves; Sayer, Avan Aihie; Schneider, Stephane M.; Sieber, Cornel C.; Topinkova, Eva; Vandewoude, Maurits; Visser, Marjolen; Zamboni, Mauro; Pitkälä, Kaisu Hannele (2019)
    Background in 2010, the European Working Group on Sarcopenia in Older People (EWGSOP) published a sarcopenia definition that aimed to foster advances in identifying and caring for people with sarcopenia. In early 2018, the Working Group met again (EWGSOP2) to update the original definition in order to reflect scientific and clinical evidence that has built over the last decade. This paper presents our updated findings. Objectives to increase consistency of research design, clinical diagnoses and ultimately, care for people with sarcopenia. Recommendations sarcopenia is a muscle disease (muscle failure) rooted in adverse muscle changes that accrue across a lifetime; sarcopenia is common among adults of older age but can also occur earlier in life. In this updated consensus paper on sarcopenia, EWGSOP2: (1) focuses on low muscle strength as a key characteristic of sarcopenia, uses detection of low muscle quantity and quality to confirm the sarcopenia diagnosis, and identifies poor physical performance as indicative of severe sarcopenia; (2) updates the clinical algorithm that can be used for sarcopenia case-finding, diagnosis and confirmation, and severity determination and (3) provides clear cut-off points for measurements of variables that identify and characterise sarcopenia. Conclusions EWGSOP2's updated recommendations aim to increase awareness of sarcopenia and its risk. With these new recommendations, EWGSOP2 calls for healthcare professionals who treat patients at risk for sarcopenia to take actions that will promote early detection and treatment. We also encourage more research in the field of sarcopenia in order to prevent or delay adverse health outcomes that incur a heavy burden for patients and healthcare systems.
  • Björkman, Mikko P.; Jyväkorpi, Satu K.; Strandberg, Timo; Pitkälä, Kaisu H.; Tilvis, Reijo S. (2020)
    BACKGROUND: Bioimpedance skeletal muscle indices (SMI) are used as a surrogate for skeletal muscle mass, but their associations with physical functioning and obesity need further evaluation. AIMS: To compare the associations of body mass index (BMI), bioimpedance spectroscopy-based calf intracellular resistance (Cri-SMI), and single-frequency bioimpedance analysis (SF-SMI) indices with physical performance and the functioning of community-dwelling older people at risk of or already suffering from sarcopenia. METHODS: Pre-intervention measurements of the screened subjects and the participants of the Porvoo sarcopenia trial (N = 428) were taken. Cri-SMI, whole-body SF-SMI, and BMI were related to hand-grip strength, walking speed, short physical performance battery (SPPB), and the physical component of the RAND-36. RESULTS: Among the older people (aged 75-96), Cri-SMI correlated inversely with age (men r = - 0.113, p < 0.001; women r = - 0.287, p < 0.001), but positively with SPPB (r = 0.241, p < 0.001) and the physical component of the RAND-36 (r = 0.114, p = 0.024), whereas BMI was inversely associated with SPPB (r = - 0.133, p < 0.001) and RAND-36 (r = - 0.286, p < 0.001). After controlling for age, gender, and comorbidity, one unit of Cri-SMI (cm2/Ω) was associated with a 3.3-fold probability of good physical performance (SPPB ≥ 9 points, OR = 3.28, p < 0.001) and one unit of BMI (kg/m2) decreased the respective probability 4% (OR= 0.96, p = 0.065). Physical inactivity partly explained the negative association of BMI. When Cri-SMI and BMI were controlled for, a 1% difference in Cri-SMI was associated with a 0.7% (p < 0.001) higher probability of good performance, the respective figure being - 2.2% (p = 0.004) for BMI. The associations of SF-SMI with physical functioning indices were insignificant. CONCLUSIONS: Independent of each other, Cri-SMI was positively and BMI was inversely associated with the physical performance and functioning of community-dwelling older people who were at risk of or already suffering from sarcopenia. We found no association between SF-SMI and physical functioning.