scholarly journals Aging Aggravates Cachexia in Tumor-Bearing Mice

Cancers ◽  
2021 ◽  
Vol 14 (1) ◽  
pp. 90
Author(s):  
Julia Geppert ◽  
Alina A. Walth ◽  
Raúl Terrón Expósito ◽  
Doris Kaltenecker ◽  
Pauline Morigny ◽  
...  

Background: Cancer is primarily a disease of high age in humans, yet most mouse studies on cancer cachexia are conducted using young adolescent mice. Given that metabolism and muscle function change with age, we hypothesized that aging may affect cachexia progression in mouse models. Methods: We compare tumor and cachexia development in young and old mice of three different strains (C57BL/6J, C57BL/6N, BALB/c) and with two different tumor cell lines (Lewis Lung Cancer, Colon26). Tumor size, body and organ weights, fiber cross-sectional area, circulating cachexia biomarkers, and molecular markers of muscle atrophy and adipose tissue wasting are shown. We correlate inflammatory markers and body weight dependent on age in patients with cancer. Results: We note fundamental differences between mouse strains. Aging aggravates weight loss in LLC-injected C57BL/6J mice, drives it in C57BL/6N mice, and does not influence weight loss in C26-injected BALB/c mice. Glucose tolerance is unchanged in cachectic young and old mice. The stress marker GDF15 is elevated in cachectic BALB/c mice independent of age and increased in old C57BL/6N and J mice. Inflammatory markers correlate significantly with weight loss only in young mice and patients. Conclusions: Aging affects cachexia development and progression in mice in a strain-dependent manner and influences the inflammatory profile in both mice and patients. Age is an important factor to consider for future cachexia studies.

2019 ◽  
Vol 26 (1) ◽  
pp. 10-20
Author(s):  
Maija Huttunen-Lenz ◽  
Sylvia Hansen ◽  
Thomas Meinert Larsen ◽  
Pia Christensen ◽  
Mathijs Drummen ◽  
...  

Abstract. Individuals at risk of Type 2 Diabetes are advised to change health habits. This study investigated how the PREMIT behavior modification intervention and its association with socio-economic variables influenced weight maintenance and habit strength in the PREVIEW study. Overweight adults with pre-diabetes were enrolled ( n = 2,224) in a multi-center RCT including a 2-month weight-loss phase and a 34-month weight-maintenance phase for those who lost ≥ 8% body weight. Initial stages of the PREMIT covered the end of weight-loss and the beginning of weight-maintenance phase (18 weeks). Cross-sectional and longitudinal data were explored. Frequent PREMIT sessions attendance, being female, and lower habit strength for poor diet were associated with lower weight re-gain. Being older and not in employment were associated with lower habit strength for physical inactivity. The PREMIT appeared to support weight loss maintenance. Younger participants, males, and those in employment appeared to struggle more with inactivity habit change and weight maintenance.


2021 ◽  
Vol 18 (1) ◽  
Author(s):  
Daniela Frasca ◽  
Maria Romero ◽  
Denisse Garcia ◽  
Alain Diaz ◽  
Bonnie B. Blomberg

Abstract Background Aging is associated with increased intrinsic B cell inflammation, decreased protective antibody responses and increased autoimmune antibody responses. The effects of aging on the metabolic phenotype of B cells and on the metabolic programs that lead to the secretion of protective versus autoimmune antibodies are not known. Methods Splenic B cells and the major splenic B cell subsets, Follicular (FO) and Age-associated B cells (ABCs), were isolated from the spleens of young and old mice and left unstimulated. The RNA was collected to measure the expression of markers associated with intrinsic inflammation and autoimmune antibody production by qPCR. B cells and B cell subsets were also stimulated with CpG and supernatants collected after 7 days to measure autoimmune IgG secretion by ELISA. Metabolic measures (oxygen consumption rate, extracellular acidification rate and glucose uptake) were performed using a Seahorse XFp extracellular flux analyzer. Results Results have identified the subset of ABCs, whose frequencies and numbers increase with age and represent the most pro-inflammatory B cell subset, as the cell type mainly if not exclusively responsible for the expression of inflammatory markers and for the secretion of autoimmune antibodies in the spleen of old mice. Hyper-inflammatory ABCs from old mice are also hyper-metabolic, as compared to those from young mice and to the subset of FO B cells, a feature needed not only to support their higher expression of RNA for inflammatory markers but also their higher autoimmune antibody secretion. Conclusions These results identify a relationship between intrinsic inflammation, metabolism and autoimmune B cells and suggest possible ways to understand cellular mechanisms that lead to the generation of pathogenic B cells, that are hyper-inflammatory and hyper-metabolic, and secrete IgG antibodies with autoimmune specificities.


2021 ◽  
Author(s):  
Larissa Cristina Lins Berber ◽  
Mariana Silva Melendez-Araújo ◽  
Eduardo Yoshio Nakano ◽  
Kênia Mara Baiocchi de Carvalho ◽  
Eliane Said Dutra

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María García-Manrique ◽  
Joan Calvet ◽  
Cristóbal Orellana ◽  
Antoni Berenguer-Llergo ◽  
Silvia Garcia-Cirera ◽  
...  

AbstractSeveral cytokines and adipokines are related to clinical severity and progression in knee osteoarthritis. The aim of this study was to evaluate the associations of IL-8 with clinical severity and with local and systemic adipokines and cytokines. This is a Cross-sectional study including 115 women with symptomatic primary knee osteoarthritis with ultrasound-confirmed joint effusion. Age, symptoms duration and body mass index were collected. Radiographic severity was evaluated according to Kellgren–Lawrence. Pain and disability were assessed by Lequesne and Knee injury and Osteoarthritis Outcome Score pain, symptoms and function scales. Three inflammatory markers and five adipokines were measured by ELISA in serum and synovial fluid. Partial correlation coefficient (PCC) and corresponding 95% confidence interval were used to evaluate association. Synovial fluid IL-8 was significantly associated with clinical severity scales. After controlling for potential confounders, associations measured by a Partial Correlation Coefficient (PCC) remained essentially unaltered for Lequesne (PCC = 0.237), KOOS pain (PCC = − 0.201) and KOOS symptoms (PCC = − 0.209), KOOS function (PCC = − 0.185), although the later did not reach statistical significance. Also in synovial fluid samples, associations were found between IL-8 and TNF (PCC = 0.334), IL6 (PCC = 0.461), osteopontin (PCC = 0.575), visfatin (PCC = 0.194) and resistin (PCC = 0.182), although significance was not achieved for the later after statistical control for confounders. None of these associations were detected in serum. In conclusion, IL-8 was associated with clinical severity, inflammatory markers and adipokines in synovial fluid, but not in blood. Although the reported associations are weak to moderate in magnitude, these findings reinforce the notion that local and not systemic inflammation is more relevant to clinical severity in knee OA women with joint effusion.


2010 ◽  
Vol 84 (16) ◽  
pp. 8172-8180 ◽  
Author(s):  
Jeffrey L. Americo ◽  
Bernard Moss ◽  
Patricia L. Earl

ABSTRACT Infection with monkeypox virus (MPXV) causes disease manifestations in humans that are similar, although usually less severe, than those of smallpox. Since routine vaccination for smallpox ceased more than 30 years ago, there is concern that MPXV could be used for bioterrorism. Thus, there is a need to develop animal models to study MPXV infection. Accordingly, we screened 38 inbred mouse strains for susceptibility to MPXV. Three highly susceptible wild-derived inbred strains were identified, of which CAST/EiJ was further developed as a model. Using an intranasal route of infection with an isolate of the Congo Basin clade of MPXV, CAST/EiJ mice exhibited weight loss, morbidity, and death in a dose-dependent manner with a calculated 50% lethal dose (LD50) of 680 PFU, whereas there were no deaths of BALB/c mice at a 10,000-fold higher dose. CAST/EiJ mice exhibited greater MPXV sensitivity when infected via the intraperitoneal route, with an LD50 of 14 PFU. Both routes resulted in MPXV replication in the lung, spleen, and liver. Intranasal infection with an isolate of the less-pathogenic West African clade yielded an LD50 of 7,600 PFU. The immune competence of CAST/EiJ mice was established by immunization with vaccinia virus, which induced antigen-specific T- and B-lymphocyte responses and fully protected mice from lethal doses of MPXV. The new mouse model has the following advantages for studying pathogenesis of MPXV, as well as for evaluation of potential vaccines and therapeutics: relative sensitivity to MPXV through multiple routes, genetic homogeneity, available immunological reagents, and commercial production.


Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Muhammad F Kazmi

Abstract Background/Aims  Rheumatological conditions can present with a number of non-specific features like arthralgia, fever, fatigue, weight loss along with raised inflammatory markers and positive antibodies. Due to this, when similar symptoms are referred for input it is very important to consider other ‘mimics’. We report a case of Pigeon fancier’s lung presenting with these symptoms which was referred as likely connective tissue disease. Methods  A 52-year-old lady of South Asian origin was referred by her GP with six month history of 3kg weight loss, arthralgia, fatigue, low grade fever and persistently raised inflammatory markers (ESR ranging from 50-64 mm/hr, CRP 10-14 mg/L, normal BMI). On further questioning there was history of mouth ulcers, non-specific rash, occasional cough but no Raynaud’s or joint swelling. Blood investigations showed weakly positive ANA and RF but negative ENA, DNA, antiCCP , CK, C3,C4. C-ANCA was positive but PR3 negative. CXR was clear and tests for chronic infections including TB were negative. Due to lack of objective CTD signs, plan was to take a careful monitoring approach to see if clinical features evolved. A month later due to worsening cough, a CT chest/abdomen arranged by GP showed ground-glass changes consistent with pneumonitis and hence her rheumatology appointment was expedited to see if there was an autoimmune unifying diagnosis. She was also referred by her GP to the chest clinic in view of CT report and mild shortness of breath. Results  On further review, again there were no objective CTD signs. On direct questioning there was history of travelling before worsening chest symptoms to South Asia. Also around a year before her symptoms started she was given an African grey parrot. Based on this, serology for Avian precipitin was checked which showed strongly positive IgG antibodies to avian antigens (Budgerigar droppings and feathers, Pigeon feathers IgG Abs) confirming the diagnosis of pigeon fanciers lung. She fulfilled the diagnostic criteria and was asked to avoid the trigger. Urgent respiratory input was arranged where diagnosis was agreed with and disease was deemed sub-acute in presentation. Due to PFTs showing low transfer factor of 38%, Prednisolone was started with significant improvement within few days. Review of CT chest only showed inflammatory changes and no established fibrosis predicting excellent prognosis as delay in treatment can cause irreversible pulmonary fibrosis. Conclusion  A number of conditions can mimic rheumatological conditions which usually turn out to be either infectious or malignant in origin. This case highlights the importance of considering other differentials and along with taking a travel history also asking for other possible triggers like pets. In similar scenarios the diagnosis may be ‘cagey’ but as rheumatologists we are expected to answers questions which others can’t. Disclosure  M.F. Kazmi: None.


2018 ◽  
Vol 64 (2) ◽  
pp. 133-139 ◽  
Author(s):  
Ana Paula Signori Urbano ◽  
Ligia Yukie Sassaki ◽  
Mariana de Souza Dorna ◽  
Paula Torres Presti ◽  
Maria Antonieta de Barros Leite Carvalhaes ◽  
...  

Summary Objective: The aim of our study was to assess body composition status and its association with inflammatory profile and extent of intestinal damage in ulcerative colitis patients during clinical remission. Method: This is a cross-sectional study in which body composition data (phase angle [PhA], fat mass [FM], triceps skin fold thickness [TSFt], mid-arm circumference [MAC], mid-arm muscle circumference [MAMC], adductor pollicis muscle thickness [APMt]), inflammatory profile (C-reactive protein [CRP], a1-acid glycoprotein, erythrocyte sedimentation rate [ESR]) and disease extent were recorded. Results: The mean age of the 59 patients was 48.1 years; 53.3% were women. Most patients were in clinical remission (94.9%) and 3.4% was malnourished according to body mass index. PhA was inversely correlated with inflammatory markers such as CRP (R=-0.59; p<0.001) and ESR (R=-0.46; p<0.001) and directly correlated with lean mass: MAMC (R=0.31; p=0.01) and APMt (R=0.47; p<0.001). Lean mass was inversely correlated with non-specific inflammation marker (APMt vs. ESR) and directly correlated with hemoglobin values (MAMC vs. hemoglobin). Logistic regression analysis revealed that body cell mass was associated with disease extent (OR 0.92; 95CI 0.87-0.97; p<0.01). Conclusion: PhA was inversely correlated with inflammatory markers and directly correlated with lean mass. Acute inflammatory markers were correlated with disease extent. Body cell mass was associated with disease extent.


2014 ◽  
Vol 14 (1) ◽  
Author(s):  
Souhiela Fakih ◽  
Jennifer L Marriott ◽  
Helen Boardman ◽  
Claire Anderson ◽  
Safeera Y Hussainy

2007 ◽  
Vol 157 (4) ◽  
pp. 419-426 ◽  
Author(s):  
David H St-Pierre ◽  
Jean-Philippe Bastard ◽  
Lise Coderre ◽  
Martin Brochu ◽  
Antony D Karelis ◽  
...  

Objective: Recent reports have suggested that the existence of associations between hormonal dysregulation and chronic upregulation of inflammatory markers, which may cause obesity-related disturbances. Thus, we examined whether acylated ghrelin (AcylG) and total ghrelin (TotG) levels could be associated with the following inflammatory markers: C-reactive protein (CRP), tumor necrosis factor α (TNF-α), and soluble TNF receptor 1 (sTNF-R1). Design: Cross-sectional study consisting of 50 overweight and obese postmenopausal women. Methods: AcylG and TotG levels were assessed at 0, 60, 160, 170, and 180 min of the euglycemic/hyperinsulinemic clamp (EHC). We evaluated insulin sensitivity, body composition, and blood lipid profiles as well as fasting concentrations of CRP, TNF-α, and sTNF-R1. Results: In fasting conditions, sTNF-R1 was negatively correlated with AcylG (r = −0.48, P < 0.001) levels. In addition, AcylG/TotG was associated negatively with sTNF-R1 (r = −0.44, P = 0.002) and positively with TNF-α (r = 0.38, P = 0.009) values. During the EHC, TotG (at all time points) and AcylG (at 60 and 160 min) values were significantly decreased from fasting concentrations. AcylG maximal reduction and area under the curve (AUC) values were correlated to sTNF-R1 (r = −0.35, P = 0.02 and r = −0.34, P = 0.02, respectively). Meanwhile, the AcylG/TotG AUC ratio was associated negatively with sTNF-R1 (r = −0.29, P < 0.05) and positively with TNF-α (r = 0.36, P = 0.02). Following adjustments for total adiposity, sTNF-R1 remained correlated with fasting and maximal reduction AcylG values. Similarly, AcylG/TotG ratios remained significantly correlated with sTNF-R1 and TNF-α. Importantly, 23% of the variation in sTNF-R1 was independently predicted by fasting AcylG. Conclusion: These results are the first to suggest that both fasting and EHC-induced AcylG profiles are correlated with fasting values of sTNF-R1, a component of the TNF-α system. Thus, AcylG may act, at least in part, as one mediator of chronic inflammatory activity in human obesity.


Sign in / Sign up

Export Citation Format

Share Document