Relation between body composition, fat distribution, and lung function in elderly men.

BACKGROUND: Body composition changes with age, with increases in fat mass and visceral fat and declines in skeletal muscle mass; lung function also declines with age. Age-related changes in body composition and fat distribution may be associated with the pulmonary impairment observed in the elderly. OBJECTIVE: Our goal was to evaluate the relations between body composition, fat distribution, and lung function in elderly men. DESIGN: We studied 97 men aged 67-78 y with body mass indexes (BMIs; in kg/m2) ranging from 19.8 to 37.1. Body composition was evaluated by using dual-energy X-ray absorptiometry and fat distribution was evaluated by using waist and hip circumferences, waist-to-hip ratio, and sagittal abdominal diameter (SAD). Spirometry was done in all subjects and the distance walked by each subject during a 6-min walking test was evaluated as was leg strength. RESULTS: A significant negative correlation was found between adiposity, fat distribution indexes, forced vital capacity (FVC), and forced expiratory volume in 1 s (FEV1). A positive correlation was found between fat-free mass and FVC. After adjustment for age, height, and weight, SAD still correlated negatively with FVC and FEV1 (r = -0.367 and -0.348, respectively; P < 0.01), whereas percentage body fat and fat mass correlated negatively and fat-free mass correlated positively with FVC (r = -0.313, -0.323, and 0.299, respectively; all P < 0.01). After the sample was subdivided by tertile of fat-free mass adjusted for age and BMI, FVC and FEV1 were significantly lower in the lowest fat-free mass tertile (P < 0.01). Stepwise multiple regression analysis performed with use of lung function variables as the dependent variables and age, height, fat mass, fat-free mass, waist circumference, and SAD as the independent variables showed that 3 variables entered the regression for predicting FVC: height, which entered the regression first; SAD, which entered second; and fat-free mass, which entered third. Only 2 variables entered the regression for predicting FEV1: height, which entered the regression first, and SAD, which entered second. CONCLUSION: Our cross-sectional data show a significant association between body composition, fat distribution, and lung function in elderly men

Weight Loss and Hypertension in Obese Subjects

Arterial hypertension is strongly related to overweight and obesity. In obese subjects, several mechanisms may lead to hypertension such as insulin and leptin resistance, perivascular adipose tissue dysfunction, renal impairment, renin-angiotensin-aldosterone-system activation and sympathetic nervous system activity. Weight loss (WL) seems to have positive effects on blood pressure (BP). The aim of this review was to explain the mechanisms linking obesity and hypertension and to evaluate the main studies assessing the effect of WL on BP. We analysed studies published in the last 10 years (13 studies either interventional or observational) showing the effect of WL on BP. Different WL strategies were taken into account-diet and lifestyle modification, pharmacological intervention and bariatric surgery. Although a positive effect of WL could be identified in each study, the main difference seems to be the magnitude and the durability of BP reduction over time. Nevertheless, further follow-up data are needed: there is still a lack of evidence about long term effects of WL on hypertension. Hence, given the significant results obtained in several recent studies, weight management should always be pursued in obese patients with hypertension

MODULAZIONE DEI FENOMENI DI SENESCENZA CELLULARE DI ADIPOCITI E PREADIPOCITI IN VITRO

L’invecchiamento è accompagnato da una complessa rete di processi biologici caratterizzati da uno stato infiammatorio cronico basale, a sua volta correlato allo sviluppo di patologie età-associate come: aterosclerosi, osteoartriti, Alzheimer, diabete di tipo 2. Una sempre più approfondita analisi del processo di senescenza tessutospecifico potrebbe consentire l’individuazione di target terapeutici utili a modulare il processo complessivo dell’invecchiamento stesso. L’invecchiamento è causa di declino delle funzionalità sistemiche e il tessuto adiposo è uno degli organi maggiormente colpiti in quanto subisce cambiamenti significativi che riguardano la quantità, la distribuzione, la composizione cellulare e l’attività endocrina, giocando un ruolo chiave nell’insorgenza di insulino-resistenza, di disfunzioni metaboliche e infiammazione sistemica. L’abbondanza del tessuto adiposo e le diverse funzioni da esso esercitate lo rendono un organo fondamentale per la comprensione della fisiologia dell’intero organismo. Tuttavia, i cambiamenti a cui è sottoposto durante il processo di invecchiamento sono solo in parte noti e oggetto di studio negli ultimi anni. È quindi fondamentale conoscere i processi molecolari che stanno alla base della fisiopatologia del tessuto adiposo e del suo invecchiamento in modo da poter individuare strategie terapeutiche per le malattie correlate all’invecchiamento. In questo studio, è stato messo a punto un modello cellulare di senescenza in vitro attraverso il trattamento con perossido di idrogeno (H2O2) in adipociti e preadipociti 3T3-L1 murini. Successivamente è stata valutata la potenziale attività senolitica della quercetina esaminandone l’effetto antiossidante e antinfiammatorio, cercando di individuarne il target molecolare.Aging is associated with pathological age-related processes as inflammatory low-grade state, atherosclerosis, Alzheimer's disease, type II diabetes and osteoarthritis diseases. A deep analysis of the tissue-specific senescence process could allow the identification of therapeutic targets to modulate the aging process itself. In this study, premature senescence model was developed in vitro through treatment with oxygen peroxide (H2O2) in murine 3T3-L1 preadipocytes before and after induction to mature adipocytes. H2O2 treated cells showed characteristic senescence-associated features including senescence-associated beta-galactosidase activity (SA-ß-gal), activation of reactive oxygen species (ROS) development of senescence-associated secretory phenotype (SASP), induction of cell cycle inhibitors P-21 as well as induction of pro-inflammatory transduction factor NFκB and a downregulation of deacetylase SIRT1. We found that stimulation with H2O2 results in an induction of miR-155-5p expression in preadipocytes and in mature adipocytes. The treatment with quercetin (20 μM) showed significant decrease in the number of ß-galactosidase positive cell along with the suppression of ROS, NFκB and SASP factor in both cell models. In addition, quercetin treatment also upregulated protein expression of SIRT1 and decreased miR-155-5p expression. These results suggest that quercetin acts as a potential senolytic agent in both preadipocytes and adipocytes cell models, inhibiting ROS production and proinflammatory miR-155-5p

Relationship between lipid droplets size and integrated optical density

Lipid accumulation is largely investigated due to its role in many human diseases. The attention is mainly focused on the lipid droplets (LDs), spherical cytoplasmic organelles which are devoted to the storage of the lipids. The amount of lipid content is often evaluated by measuring LDs size and/or the integrated optical density (IOD) in cultured cells. Both evaluations are directly associated to the lipid content and therefore they are correlated to each other, but a lack of theoretical relationship between size and IOD was observed in literature. Here we investigated the size-IOD relationship of LDs observed in microscopical images of cultured cells. The experimental data were obtained from immature and differentiated 3T3-L1 murine cells, which have been extensively used in studies on adipogenesis. A simple model based on the spherical shape of the LDs and the Lambert-Beer law, which describes the light absorption by an optical thick material, leads to a mathematical relationship. Despite only light rays\u2019 absorption was considered in the model, neglecting their scattering, a very good agreement between the theoretical curve and the experimental data was found. Moreover, a computational simulation corroborates the model indicating the validity of the mathematically theoretical relationship between size and IOD. The theoretical model could be used to calculate the absorption coefficient in the LDs population and it could be applied to seek for morphologically and functionally LDs subpopulations. The identification of LDs dynamic by measuring size and IOD could be related to different pathophysiological conditions and useful for understand cellular lipid-associated diseases

Systemic inflammation, body composition, and physical performance in old community-dwellers

Background Chronic inflammation, changes in body composition, and declining physical function are hallmarks of the ageing process. The aim of the present study was to provide a preliminary characterisation of the relationship among these age-related phenomena via multivariate modelling. Methods Thirty-five old adults (OAs) and 17 young adults (YAs) were enrolled. The volume of skeletal muscle, subcutaneous adipose tissue (SAT), and intermuscular adipose tissue (IMAT) of the thigh was quantified by three-dimensional magnetic resonance imaging. Muscle strength was measured by knee extension strength testing. In OAs, physical performance was further assessed via the Short Physical Performance Battery (SPPB). Multi-block partial least squares-discriminant analysis (PLS-DA) was employed to explore the relationship among inflammatory profiles and functional and imaging parameters. Double cross-validation procedures were used to validate the predictive ability of the PLS-DA model. Results The optimal complexity of the PLS-DA model was found to be two latent variables. The proportion of correct classification was 92.3% in calibration (94.1% in YAs and 91.4% in OAs), 84.6% in internal validation (95.3% in YAs and 78.5% in OAs), and 82.6% in external validation (94% in YAs and 76.9% in OAs). Relative to YAs, OAs were characterised by smaller muscle volume, greater IMAT volume, lower muscle strength, and higher levels of myeloperoxidase, P-selectin, soluble intercellular adhesion molecule 1, and vascular cell adhesion molecule 1. Compared with OAs with SPPB &gt;8, those scoring 8 were characterised by smaller muscle volume, greater SAT volume, lower muscle strength, and higher levels of interleukin 1 beta, 6, 10, 12, 13, tumour necrosis factor alpha, and granulocyte-macrophage colony-stimulating factor. Conclusions Multi-block PLS-DA identified distinct patterns of relationships among circulating cytokines and functional and imaging parameters in persons of different ages and varying levels of physical performance. The longitudinal implementation of such an innovative strategy could allow for the tracking of health status over time, the early detection of deviations in health trajectories, and the monitoring of response to treatments

Brown and Beige Adipose Tissue and Aging

Across aging, adipose tissue (AT) changes its quantity and distribution: AT becomes dysfunctional with an increase in production of inflammatory peptides, a decline of those with anti-inflammatory activity and infiltration of macrophages. Adipose organ dysfunction may lead to age-related metabolic alterations. Aging is characterized by an increase in adiposity and a decline in brown adipose tissue (BAT) depots and activity, and UCP1 expression. There are many possible links to age-associated involution of BAT, including the loss of mitochondrial function, impairment of the sympathetic nervous system, age-induced alteration of brown adipogenic stem/progenitor cell function and changes in endocrine signals. Aging is also associated with a reduction in beige adipocyte formation. Beige adipocytes are known to differentiate from a sub-population of progenitors resident in white adipose tissue (WAT); a defective ability of progenitor cells to proliferate and differentiate has been hypothesized with aging. The loss of beige adipocytes with age may be caused by changes in trophic factors in the adipose tissue microenvironment, which regulate progenitor cell proliferation and differentiation. This review focuses on possible mechanisms involved in the reduction of BAT and beige activity with aging, along with possible targets for age-related metabolic disease therapy

Arterial Stiffness, Subendocardial Impairment, and 30-Day Readmission in Heart Failure Older Patients

Arterial stiffness and subendocardial perfusion impairment may play a significant role in heart failure (HF) outcomes. The aim of the study was to examine the main predictors of 30-day readmission in geriatric patients, hospitalized with HF, explore hemodynamical parameters, arterial stiffness indexes, and subendocardial viability ratio (SEVR). In total, 41 hospitalized patients, affected by HF, were included; they underwent clinical evaluation, routine laboratory testing, and echocardiography. At the time of admission, after the achievement of clinical stability (defined as switching from intravenous to oral diuretic therapy), and at discharge, arterial tonometry was performed to evaluate carotid-femoral pulse wave velocity (PWVcf) and SEVR (then corrected for hemoglobin concentration and oxygen saturation). Through the evaluations, a significant progressive decrease in PWVcf was described (17.79 ± 4.49, 13.54 ± 4.54, and 9.94 ± 3.73 m/s), even after adjustment for age, gender, mean arterial pressure (MAP) variation, and left ventricular ejection fraction (LVEF). A significant improvement was registered for both SEVR (83.48 ± 24.43, 97.94 ± 26.84, and 113.29 ± 38.02) and corrected SEVR (12.74 ± 4.69, 15.71 ± 5.30, and 18.55 ± 6.66) values, and it was still significant when adjusted for age, gender, MAP variation, and LVEF. After discharge, 26.8% of patients were readmitted within 30 days. In a multivariate binary logistic regression analysis, PWVcf at discharge was the only predictor of 30-day readmission (odds ratio [OR] 1.957, 95% CI 1.112-3.443). In conclusion, medical therapy seems to improve arterial stiffness and subendocardial perfusion in geriatric patients hospitalized with heart failure. Furthermore, PWVcf is a valid predictor of 30-day readmission. Its feasibility in clinical practice may provide an instrument to detect patients with HF at high risk of rehospitalization

Sarcopenia, sarcopenic obesity, and arterial stiffness among older adults

Background: Aging is associated with a higher prevalence of sarcopenia, sarcopenic obesity (SO), and increased arterial stiffening, with possible detrimental effects on morbidity and mortality. The aim of this study was to assess the relationships between sarcopenia, SO, and different indexes of arterial stiffness in older adults. Methods: A total of 77 hospitalized patients (mean age 78.68 ± 9.65 years) were evaluated, obtaining anthropometric variables, biochemical samples, handgrip test, and body composition assessment. Arterial stiffness was evaluated by measuring both carotid-femoral pulse wave velocity (cfPWV), a proxy for central stiffness, and cardio-ankle vascular index (CAVI), as well as considering peripheral arteries. The population was sorted into four subgroups: obese, sarcopenic, SO, and controls. Results: The highest CAVI (11.31 ± 2.58) was found in sarcopenic patients. SO had the highest value of cfPWV (15.18 ± 8.44 m/s), even after adjustment for significant covariates. In multiple regressions, SO diagnosis resulted as a significant predictor of cfPWV (p = 0.03, R2 = 0.20), and sarcopenia diagnosis resulted as a predictor of CAVI (p = 0.042, R2 = 0.12). Conclusions: In conclusion, a positive correlation is found between sarcopenia, SO, and arterial stiffness among older subjects. In particular, greater central arterial stiffness is associated with SO, outlining a remarkable effect on the cardiovascular risk profile

Myocardial fibrosis and steatosis in patients with aortic stenosis: roles of myostatin and ceramides

Aortic stenosis (AS) involves progressive valve obstruction and a remodeling response of the left ventriculum (LV) with systolic and diastolic dysfunction. The roles of interstitial fibrosis and myocardial steatosis in LV dysfunction in AS have not been completely characterized. We enrolled 31 patients (19 women and 12 men) with severe AS undergoing elective aortic valve replacement. The subjects were clinically evaluated, and transthoracic echocardiography was performed pre-surgery. LV septal biopsies were obtained to assess fibrosis and apoptosis and fat deposition in myocytes (perilipin 5 (PLIN5)), or in the form of adipocytes within the heart (perilipin 1 (PLIN1)), the presence of ceramides and myostatin were assessed via immunohistochemistry. After BMI adjustment, we found a positive association between fibrosis and apoptotic cardiomyocytes, as well as fibrosis and the area covered by PLIN5. Apoptosis and PLIN5 were also significantly interrelated. LV fibrosis increased with a higher medium gradient (MG) and peak gradient (PG). Ceramides and myostatin levels were higher in patients within the higher MG and PG tertiles. In the linear regression analysis, increased fibrosis correlated with increased apoptosis and myostatin, independent from confounding factors. After adjustment for age and BMI, we found a positive relationship between PLIN5 and E/A and a negative correlation between septal S', global longitudinal strain (GLS), and fibrosis. Myostatin was inversely correlated with GLS and ejection fraction. Fibrosis and myocardial steatosis altogether contribute to ventricular dysfunction in severe AS. The association of myostatin and fibrosis with systolic dysfunction, as well as between myocardial steatosis and diastolic dysfunction, highlights potential therapeutic targets

Effect of moderate weight loss on hepatic, pancreatic and visceral lipids in obese subjects

OBJECTIVE: To compare the effects of weight loss on visceral and subcutaneous abdominal fat, liver and pancreas lipid contentand to test the effects of these changes on metabolic improvement observed after weight loss.DESIGN: Weight-loss program designed to achieve a loss of 7--10% of the initial weight.SUBJECTS: 24 obese subjects (13 males and 11 females) with age ranging from 26 to 69 years and body mass index (BMI)30.2 -- 50.5 kgm2. Measurements: weight, BMI, waist circumference, body composition as assessed by dual-energy X-rayabsorptiometry, metabolic variables, leptin, adiponectin, visceral and subcutaneous abdominal fat, liver and pancreas lipidcontent as assessed by magnetic resonance were evaluated before and after weight loss achieved by hypocaloric diet.RESULTS: After a mean body weight decrease of 8.9%, BMI, waist circumference, fat mass, all metabolic variables, homeostasismodel assessment of insulin resistance (HOMA), alanine amino transferase, gamma glutamyl transpeptidase, high-sensitivityC-reactive protein (hs-CRP) and leptin, but not adiponectin and high-density lipoprotein-cholesterol, significantly decreased (allPo0.01). Visceral and subcutaneos abdominal fat, liver and pancreas lipid content significantly decreased (all Po0.01). Percentchanges in liver lipid content were greater (84.1\ub13%) than those in lipid pancreas content (42.3\ub129%) and visceral abdominalfat (31.9\ub115.6%). After weight loss, percentage of subjects with liver steatosis decreased from 75 to 12.5%. Insulin resistanceimprovement was predicted by changes in liver lipid content independently of changes in visceral fat, pancreas lipid content,systemic inflammation, leptin and gender.CONCLUSION: Moderate weight loss determines significant decline in visceral abdominal fat, lipid content in liver andpancreas. Reduction of liver lipid content was greater than that of pancreas lipid content and visceral fat loss. Liver lipidcontent is the strongest predictor of insulin resistance improvement after weight loss