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

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

Predictors of hospital readmission rate in geriatric patients

Background: Hospital readmissions among older adults are associated with progressive functional worsening, increased institutionalization and mortality. Aim: Identify the main predictors of readmission in older adults. Methods: We examined readmission predictors in 777 hospitalized subjects (mean age 84.40 ± 6.77&nbsp;years) assessed with Comprehensive Geriatric Assessment&nbsp;(CGA), clinical, anthropometric and biochemical evaluations. Comorbidity burden was estimated by Charlson Comorbidity Index (CCI). Median follow-up was 365&nbsp;days. Results: 358 patients (46.1%) had a second admission within 365&nbsp;days of discharge. Estimated probability of having a second admission was 0.119 (95%C.I. 0.095-0.141), 0.158 (95%C.I. 0.131-0.183), and 0.496 (95%C.I. 0.458-0.532) at 21, 30 and 356&nbsp;days, respectively. Main predictors of readmission at 1&nbsp;year were length of stay (LOS) &gt; 14&nbsp;days (p &lt; 0.001), albumin level &lt; 30&nbsp;g/l (p 0.018), values of glomerular filtration rate (eGFR) &lt; 40&nbsp;ml/min (p &lt; 0.001), systolic blood pressure &lt; 115&nbsp;mmHg (p &lt; 0.001), CCI ≥ 6 (p &lt; 0.001), and cardiovascular diagnoses. When the joint effects of selected prognostic variables were accounted for, LOS &gt; 14&nbsp;days, worse renal function, systolic blood pressure &lt; 115&nbsp;mmHg, higher comorbidity burden remained independently associated with higher readmission risk. Discussion: Selected predictors are associated with higher readmission risk, and the relationship evolves with time. Conclusions: This study highlights the importance of performing an accurate CGA, since defined domains and variables contained in the CGA (i.e., LOS, lower albumin and systolic blood pressure, poor renal function, and greater comorbidity burden), when combined altogether, may offer a valid tool to identify the most fragile patients with clinical and functional impairment enhancing their risk of unplanned early and late readmission

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

Senescent adipocytes as potential effectors of muscle cells dysfunction: An in vitro model

Recently, there has been a growing body of evidence showing a negative effect of the white adipose tissue (WAT) dysfunction on the skeletal muscle function and quality. However, little is known about the effects of senescent adipocytes on muscle cells. Therefore, to explore potential mechanisms involved in age-related loss of muscle mass and function, we performed an in vitro experiment using conditioned medium obtained from cultures of mature and aged 3 T3-L1 adipocytes, as well as from cultures of dysfunctional adipocytes exposed to oxidative stress or high insulin doses, to treat C2C12 myocytes. The results from morphological measures indicated a significant decrease in diameter and fusion index of myotubes after treatment with medium of aged or stressed adipocytes. Aged and stressed adipocytes presented different morphological characteristics as well as a different gene expression profile of proinflammatory cytokines and ROS production. In myocytes treated with different adipocytes' conditioned media, we demonstrated a significant reduction of gene expression of myogenic differentiation markers as well as a significant increase of genes involved in atrophy. Finally, a significant reduction in protein synthesis as well as a significant increase of myostatin was found in muscle cells treated with medium of aged or stressed adipocytes compared to controls. In conclusion, these preliminary results suggest that aged adipocytes could influence negatively trophism, function and regenerative capacity of myocytes by a paracrine network of signaling

Adipocytes WNT5a mediated dedifferentiation: a possible target in pancreatic cancer microenvironment

A significant epidemiological association between obesity and pancreatic ductal adenocarcinoma (PDAC) has previously been described, as well as a correlation between the degree of pancreatic steatosis, PDAC risk and prognosis. The underlying mechanisms are still not completely known.After co-culture of 3T3-L1 adipocytes and MiaPaCa2 with an in vitro transwell system we observed the appearance of fibroblast-like cells, along with a decrease in number and size of remaining adipocytes. RT-PCR analyses of 3T3-L1 adipocytes in co-culture showed a decrease in gene expression of typical markers of mature adipocytes, in parallel with an increased expression of fibroblast-specific and reprogramming genes. We found an increased WNT5a gene and protein expression early in MiaPaCa2 cells in co-culture. Additionally, EMSA of c-Jun and AP1 in 3T3-L1 demonstrated an increased activation in adipocytes after co-culture. Treatment with WNT5a neutralizing antibody completely reverted the activation of c-Jun and AP1 observed in co-cultured adipocytes.Increasing doses of recombinant SFRP-5, a competitive inhibitor for WNT5a receptor, added to the co-culture medium, were able to block the dedifferentiation of adipocytes in co-culture.These data support a WNT5a-mediated dedifferentiation process with adipocytes reprogramming toward fibroblast-like cells that might profoundly influence cancer microenvironment

Adipokines and arterial stiffness in the elderly

Introduction: The aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV> 10 m/s. Methods: In each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV). Results: In the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61). Conclusion: In conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness