Brown and Beige Adipose Tissue and Aging Zoico, Elena; Rubele, Sofia; De Caro, Annamaria ...
Frontiers in endocrinology (Lausanne),
06/2019, Letnik:
10
Journal Article
Recenzirano
Odprti dostop
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.
Abstract Background and aim In elderly patients, age-related changes in body composition, as well as the increased prevalence of obesity, determine a combination of excess weight and reduced muscle ...mass or strength, recently defined as sarcopenic obesity (SO). This review examines the main studies regarding sarcopenic obesity in the elderly. Data synthesis Definition of SO necessarily combines those of sarcopenia and obesity. The prevalence of sarcopenia and SO increases with age. Muscle and fat mass are strongly interconnected from a pathogenetic point of view. A better understanding of the mechanisms which lead from loss of muscle mass to fat gain or vice versa from fat gain to muscle loss seems to be crucial. Recent data suggest that peptides produced by adipose tissue may play an important role in the pathophysiology of SO, thus more research is needed to better characterize this new area. Obesity and Sarcopenia in the elderly may potentiate each other maximizing their effects on disability, morbidity and mortality. Identifying elderly subjects with SO should be mandatory; effective treatment of sarcopenia and SO may attenuate its clinical impact. Conclusion The concept of SO may help to clarify the relationship between obesity, morbidity and mortality in the elderly.
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.
•Senescent adipocytes negatively influence myocytes trophism.•Senescent adipocytes alter expression of genes involved in muscle atrophy.•Senescent and stressed adipocytes tendentially reduce protein synthesis in myocytes.•Myocytes exposition to aged adipocytes medium activates myostatin pathway.
The dysfunction of adipose tissue with aging and the accumulation of senescent cells has been implicated in the pathophysiology of chronic diseases. Recently interventions capable of reducing the ...burden of senescent cells and in particular the identification of a new class of drugs termed senolytics have been object of extensive investigation. We used an in vitro model of induced senescence by treating both pre-adipocytes as well as mature adipocytes with hydrogen peroxide (H
O
) at a sub-lethal concentration for 3 h for three consecutive days, and hereafter with 20 uM quercetin at a dose that in preliminary experiments resulted to be senolytic without cytotoxicity. H
O
treated pre-adipocytes and adipocytes showed typical senescence-associated features including increased beta-galactosidase activity (SA-ß-gal) and p21, activation of ROS and increased expression of pro-inflammatory cytokines. The treatment with quercetin in senescent pre-adipocytes and adipocytes was associated to a significant decrease in the number of the SA-β-gal positive cells along with the suppression of ROS and of inflammatory cytokines. Besides, quercetin treatment decreased miR-155-5p expression in both models, with down-regulation of p65 and a trend toward an up-regulation of SIRT-1 in complete cell extracts. The senolytic compound quercetin could affect AT ageing by reducing senescence, induced in our in vitro model by oxidative stress. The downregulation of miRNA-155-5p, possibly through the modulation of NF-κB and SIRT-1, could have a key role in the effects of quercetin on both pre-adipocytes and adipocytes.
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.
Objectives
To investigate the correlation between sarcopenia and arterial stiffness in Caucasians, centering on the relationship between skeletal mass index (SMI) and the cardio‐ankle vascular index ...(CAVI) to assess the use of CAVI in predicting sarcopenia.
Design Cross‐sectional Setting
United Kingdom.
Participants
UK adults aged 45 years and over (N = 366, n = 177 male, n = 189 female).
Measurements
Bioimpedance analysis was used to derive SMI. CAVI score was calculated using a vascular screening system. Handgrip strength was measured using a standard dynamometer.
Results
Average CAVI was significantly correlated with SMI (correlation coefficient (r) = −0.285, p < .001), with higher correlation in women (r = −0.416, p < .001) than men (r = −0.214, p = .01). CAVI had the highest correlation with SMI from appendicular muscle (fat‐free mass in men, r = −0.253, p = .002; predicted muscle mass in women, r = −0.436, p < .001). There was a significant difference in average CAVI between groups, with participants who were not sarcopenic having lower CAVI (8.98) than those who were sarcopenic (9.80) (p < .001, t‐test). Linear regression was performed using SMI as the dependent variable. After adjustment for age, average CAVI was a significant predictor of SMI in women (beta = −0.332, p < .001) but not men.
Conclusion
Indices of sarcopenia are independently associated with a higher CAVI, with greater correlation in women than men. The CAVI can be used to assess overall vascular compliance and may be a useful operator‐independent tool that can be used to measure sarcopenia and its cardiovascular implications in older adults. J Am Geriatr Soc 67:317–322, 2019.
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.
Mitochondria, essential eukaryotic cells organelles defined as the "powerhouse of the cell" because of their ability to produce the vast majority of energy necessary for cellular metabolism, may have ...a primary role in the oxidative stress-related intracellular machinery associated to chronic kidney disease (CKD).
To better assess this research assumption, we decided to study the key factors regulating mitochondrial oxidative metabolism in CKD patients in peritoneal dialysis (PD, n = 15) using several bio-molecular methodologies.
RT-PCR experiments demonstrate that the expression level of peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α) and nuclear respiratory factor-1 (NRF-1), two genes primarily involved in mitochondrial biogenesis and functions, were significantly hypo-expressed in peripheral blood mononuclear cells of PD patients compared to healthy subjects (HS, n = 15). Additionally, mRNA levels of several PGC1-α downstream target genes (TFAM, COX6C,COX7C, UQCRH and MCAD) were profoundly down-regulated in PD cells. TFAM protein analysis confirmed gene-expression results. High plasmatic concentration of Malondialdehyde found in PD patients, confirmed the contribution of the oxidative stress to these biological effects. Finally, Nuclear factor erythroid-derived 2-like 2 (NRF2 or NFE2L2), a transcription factor for numerous antioxidant/detoxifying enzymes and one of its target genes, superoxide dismutase-2 mitochondrial (SOD2) were up-regulated in PD compared to HS.
Our results revealed, for the first time, that CKD-PD patients' PBMC, through a complex intracellular biochemical machinery, are able to modulate their mitochondrial functions probably in the attempt to reduce oxidative metabolic damage and to turn on a valuable defense cellular strategy against oxidative stress.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Cochlear implants (CI) have been developed to enable satisfying verbal communication, while music perception has remained in the background in both the research and technological development, thus ...making CI users dissatisfied by the experience of listening to music. Indications for clinicians to test and train music abilities are at a preliminary stage compared to the existing and well-established hearing and speech rehabilitation programs. The main aim of the present study was to test the utility of the application of two different patient reporting outcome (PRO) measures in a group of CI users. A secondary objective was to identify items capable of driving the indication and design specific music rehabilitation programs for CI patients.
A consecutive series of 73 CI patients referred to the Audiology Unit, University of Padova, was enrolled from November 2021 to May 2022 and evaluated with the audiological battery test and PRO measures: Musica e Qualità della Vita (MUSQUAV) and Nijmegen Cochlear Implant Questionnaire (NCIQ) Italian version.
The reliability analysis showed good consistency between the different PRO measures (Cronbach's alpha = 0.873). After accounting for the epidemiological and clinical variables, the PRO measures showed a correlation with audiological outcomes in only one case (rho = -0.304; adj.
= 0.039) for NCIQ-T with the CI-pure tone average. A willingness for musical rehabilitation was present in 63% of patients (Rehab Factor, mean value of 0.791 ± 0.675).
We support the role of the application of MUSQUAV and NCIQ to improve the clinical and audiological evaluation of CI patients. Moreover, we proposed a derivative item, called the rehab factor, which could be used in clinical practice and future studies to clarify the indication and priority of specific music rehabilitation programs.
Arterial hypertension (AH) is considered to be one of the most relevant cardiovascular risk factors, and its wide prevalence in all age ranges makes it necessary to analyse all the possible causes ...and treatments. In this special issue, nutritional interventions are examined either as causes or as treatments of AH. ....
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