RESUMO
BACKGROUND: Aging is characterized by a progressive loss of capacities linked to fundamental alterations/damage in multiple cellular and molecular pathways. It is the most significant risk factor for all non-communicable diseases (NCDs). Another contributing factor to the rise in NCDs is obesity. It has been suggested that obesity not only accelerates the onset of metabolic imbalances but also decreases lifespan and impacts cellular and molecular processes in a manner similar to aging. Obesity might accelerate the pace of aging. Guided by a lifecourse approach, we will explore how exposure to obesity in critical developmental stages disrupt homeostatic resilience mechanisms that preserve physiological integrity, inducing an early expression of aging phenotypes. Also, we will determine whether exposure to early psychosocial adversity influences vulnerability to obesity as a risk factor for accelerated aging. METHODS: Multiple events case-control study embedded in a prospective cohort of Chileans at 30-31y, 50% females, of low- to-middle socioeconomic status, who participated in nutrition research since birth. At 23y, 25% had obesity and cardiometabolic risk was high. We will use a multi-layer approach including: anthropometric assessment; DXA scan for body composition; abdominal ultrasound of the liver; stool samples collection and sequencing of the ribosomal RNA 16S gene to characterize the gut microbiome; determination of age-related pro-inflammatory cytokynes and anti-inflammatory miokynes. For the first time in Chile, we will address age-related epigenetic changes using the Horvath´s epigenetic clock. In a subset we will conduct a controlled physical challenge to characterize physical resilience (autophagy). DISCUSSION: ObAGE is in an excellent position to: approach aging as a process whose expression involves multiple factors from the early stages of a person's life; understand how longitudinal changes in health trajectories impact the biological mechanisms of aging; identify potential resilience mechanisms that help prevent unhealthy aging. Because SLS participants are still young, our research setting combined with advanced scientific techniques may identify individuals or groups at risk of early onset health issues. Results from ObAGE may pave the way to address the contribution of obesity to aging through lifespan from cells to systems and might be instrumental to developing interventions to improve health span in the Chilean population. TRIAL REGISTRATION: The proposed study does not consider any health care intervention on human participants.
Assuntos
Envelhecimento , Obesidade , Envelhecimento/fisiologia , Biomarcadores , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Obesidade/diagnóstico , Obesidade/epidemiologia , Estudos ProspectivosRESUMO
BACKGROUND: While the genetic contribution to obesity is well established, few studies have examined how genetic variants influence standardized body mass index Z-score (BMIz) in Hispanics/Latinos, especially across childhood and adolescence. OBJECTIVES: We estimated the effect of established BMIz loci in Chilean children of the Santiago Longitudinal Study (SLS). METHODS: We examined associations with BMIz at age 10 for 15 loci previously identified in European children. For significant loci, we performed association analyses at ages 5 and 16 years, for which we have smaller sample sizes. We tested associations of unweighted genetic risk scores (GRSs) for previously identified tag variants (GRS_EUR) and from the most significant variants in SLS at each locus (GRS_SLS). RESULTS: We generalized five variants at age 10 (P < 0.05 and directionally consistent), including rs543874 that reached Bonferroni-corrected significance. The effect on BMIz was greatest at age 10 for all significant loci, except FTO, which exhibited an increase in effect from ages 5 to 16. Both GRSs were associated with BMIz (P < 0.0001), but GRS_SLS explained a much greater proportion of the variation (13.63%). CONCLUSION: Our results underscore the importance of conducting genetic investigations across life stages and selecting ancestry appropriate tag variants in future studies for disease prediction and clinical evaluation.
Assuntos
Índice de Massa Corporal , Obesidade Infantil/genética , Adolescente , Criança , Desenvolvimento Infantil/fisiologia , Pré-Escolar , Chile , Estudos de Coortes , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Estudos Longitudinais , Masculino , Polimorfismo de Nucleotídeo Único , Fatores de RiscoRESUMO
BACKGROUND: Sarcopenia is the progressive loss of mass and skeletal muscle strength and has serious consequences on older people's health. The Chilean older population has a high life-expectancy, but the prevalence of functional dependence is also high. OBJECTIVE: To determine the prevalence of sarcopenia in Chilean older adults and its relationship with age, gender, and body mass index (BMI). DESIGN: Cross-sectional study. SETTING: Community. PARTICIPANTS: 1,006 non-disabled, community-dwelling subjects aged 60 years or older living in Santiago. MEASUREMENTS: Anthropometric measurements, handgrip strength, physical performance tests, and dual-energy-x-ray-absorptiometry (DXA) scan were performed. Sarcopenia was defined using the algorithm of the European Working Group on Sarcopenia in Older People (EWGSOP). Muscle mass was measured with DXA scan; skeletal muscle mass index (SMI) and hand dynamometry were defined with cut-off points obtained for the Chilean population. For a 3m walking speed we used the cut-off point of the EWGSOP definition. Nutritional status and obesity were defined according to World Health Organization standards. Association between sarcopenia and age, gender, BMI and lean/fat mass ratio was estimated by logistic regression models. RESULTS: The prevalence of sarcopenia was 19.1% (95%CI: 16.8%-21.8%), similar in men and women. There was an increasing trend of sarcopenia by age group and a decreasing trend with nutritional status. After logistic regression, sarcopenia was positively associated with age (OR=1.10; 95%CI:1.06-1.15) and falls (OR=1.83; 95%CI:1.07-3.15) and negatively associated with overweight (OR=0.31; 95%CI:0.16-0.59), obesity (OR=0.02; 95%CI:0.004-0.11), lean mass/fat mass ratio (OR=0.69; 95%CI:0.48-0.9997), knee height (OR=0.78; 95%CI:0.68-0.89) and calf circumference (OR=0.87; 95%CI:0.77-0.97). CONCLUSIONS: The total prevalence of sarcopenia was 19.1% increasing with age reaching 39.6% in people of 80 or more years of age. A negative association of sarcopenia with overweight, obesity and lean/fat mass ratio was observed. Although the high prevalence of obesity (35.9%), only 2% of obese people were sarcopenic.
Assuntos
Avaliação Geriátrica/métodos , Força da Mão , Obesidade , Sarcopenia , Absorciometria de Fóton/métodos , Atividades Cotidianas , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Antropometria/métodos , Chile/epidemiologia , Feminino , Humanos , Vida Independente , Masculino , Pessoa de Meia-Idade , Obesidade/diagnóstico , Obesidade/epidemiologia , Prevalência , Fatores de Risco , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Fatores Sexuais , Estatística como AssuntoRESUMO
BACKGROUND: Increased cardiometabolic risk (CMR) is documented in obese and non-obese adolescents with low muscular fitness. However, the association of low muscle mass (LMM) with CMR, independent of weight status, has not been examined. We analyzed the relationship of LMM with CMR in adolescents, regardless of their weight status. MATERIALS AND METHODS: Observational study in 660 adolescents. BMI, waist circumference (WC), arterial blood pressures (ABP) were measured. Total fat mass (TFM), total lean tissue (TLT), and appendicular skeletal muscle mass (ASM) were estimated (DXA). Fasting lipid profile, glucose, and insulin were measured. HOMA-IR was estimated. Metabolic Syndrome (MetS) was diagnosed (AHA/NHLBI/IDF). ROC analysis was performed to find the optimal cutoffs of TLT percentage for MetS diagnosis. Values below these cutoffs defined LMM. ANCOVA examined the association of LMM with selected cardiometabolic biomarkers. RESULTS: In both sexes, TLT showed better sensitivity and specificity than ASM for MetS diagnosis. In males and females, TLT of 66.1% and 56.3%, respectively, were the optimal cutoff for MetS diagnosis. In the sample, 17.3% of males and 23.7% of females had LMM. In both sexes, adolescents with LMM had significantly higher values of WC, ABP, TG, TC/HDL, HOMA-IR, and MetS z-score than non-LMM participants. Adolescents with LMM, regardless nutritional status, had significantly increased values of MetS z-score, ABP, TG, TC/HDL-chol, and HOMA-IR than non-obese non-LMM adolescents. Adolescents having both obesity and LMM had the unhealthiest CMR profile. CONCLUSION: In adolescents, LMM was associated with higher CMR, regardless of nutritional status. In obese adolescents, LMM increased obesity-associated CMR.
Assuntos
Composição Corporal , Síndrome Metabólica/epidemiologia , Músculo Esquelético , Estado Nutricional , Adolescente , Chile/epidemiologia , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Masculino , Síndrome Metabólica/etiologia , Obesidade/complicações , Medição de RiscoRESUMO
OBJECTIVE: To determine the optimal cutoff of the homeostasis model assessment-insulin resistance (HOMA-IR) for diagnosis of the metabolic syndrome (MetS) in adolescents and examine whether insulin resistance (IR), determined by this method, was related to genetic, biological, and environmental factors. METHODS: In 667 adolescents (16.8 ± 0.3 y), BMI, waist circumference, glucose, insulin, adiponectin, diet, and physical activity were measured. Fat and fat-free mass were assessed by dual-energy X-ray absorptiometry. Family history of type 2 diabetes (FHDM) was reported. We determined the optimal cutoff of HOMA-IR to diagnose MetS (IDF criteria) using ROC analysis. IR was defined as HOMA-IR values above the cutoff. We tested the influence of genetic, biological, and environmental factors on IR using logistic regression analyses. RESULTS: Of the participants, 16% were obese and 9.4 % met criteria for MetS. The optimal cutoff for MetS diagnosis was a HOMA-IR value of 2.6. Based on this value, 16.3% of participants had IR. Adolescents with IR had a significantly higher prevalence of obesity, abdominal obesity, fasting hyperglycemia, and MetS compared to those who were not IR. FHDM, sarcopenia, obesity, and low adiponectin significantly increased the risk of IR. CONCLUSIONS: In adolescents, HOMA-IR ≥ 2.6 was associated with greater cardiometabolic risk.
Assuntos
Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/genética , Resistência à Insulina , Absorciometria de Fóton , Adolescente , Antropometria , Composição Corporal , Índice de Massa Corporal , Doenças Cardiovasculares/epidemiologia , Chile , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/epidemiologia , Meio Ambiente , Exposição Ambiental , Feminino , Homeostase , Humanos , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/epidemiologia , Obesidade/sangue , Obesidade/complicações , Obesidade/diagnóstico , Curva ROC , Análise de Regressão , Fatores de Risco , Fatores Sexuais , Inquéritos e Questionários , População Urbana , Circunferência da CinturaRESUMO
OBJECTIVES: The effectiveness of community level interventions depends to a great extent on adherence. Currently, information on factors related to adherence in older adults from developing countries is scarce. Our aim was to identify factors associated to adherence to a physical activity intervention in older adults from a post-transitional middle income country. DESIGN, SETTING AND PARTICIPANTS: Using a combination of quantitative and qualitative methods we studied 996 older Chilean subjects (65-67.9 years at baseline) with low to medium socioeconomic status from 10 health centers randomized to receive a physical activity intervention as part of the CENEX cluster trial (ISRCTN48153354). MEASUREMENTS: Using a multilevel regression model, the relationship between adherence (defined a priori as attendance at a minimum of 24 physical activity classes spread over at least 12 months) and individual, intervention-related and contextual factors was evaluated. We also conducted 40 semi-structured interviews with older adults (n=36) and instructors (n=4). Transcripts of the interviews were analyzed using content analysis to identify barriers and facilitators to adherence. RESULTS: Adherence to physical activity intervention was 42.6% (CI 95% 39.5 to 45.6). Depression, diabetes mellitus, percentage of impoverished households and rate of arrests for violent crimes in the neighborhood predicted less adherence (p<0.05) while being retired, participation in physical activity prior to the intervention, and green areas per habitant were positively associated with adherence (p<0.05). The qualitative interviews identified three primary barriers to adherence: current health problems, lack of time due to commitments for caring for family members, and being employed, and two primary facilitators to adherence: the health benefits attributed to the intervention and the opportunity the classes provided for social interaction with others. CONCLUSION: In order to enhance effectiveness of community exercise interventions, strategies to improve participation should be targeted to older adults from deprived areas and those with psychological and medical conditions.
Assuntos
Emprego , Exercício Físico , Família , Nível de Saúde , Cooperação do Paciente , Pobreza , Características de Residência , Idoso , Cuidadores , Chile , Crime , Países em Desenvolvimento , Meio Ambiente , Feminino , Comportamentos Relacionados com a Saúde , Humanos , Relações Interpessoais , Entrevistas como Assunto , Masculino , Satisfação do Paciente , Pesquisa Qualitativa , Análise de RegressãoRESUMO
It has been proposed that functional mutations in the melanocortin 4 receptor (MC4R) gene have an important impact in body mass index, being considered as a major susceptibility gene for obesity. A number of mutations have been reported in the MC4R gene in subjects from different countries and ethnic groups. However, no reports of MC4R mutations are have been published for South American populations. In this study, DNA samples of thirty-two unrelated obese women of Chilean origin were examined to search for genetic variants in the single exon of the gene through the use of single strand conformational polymorphism techniques and direct sequencing, leading to the identification of a Thr150Ile mutation in heterozygous status. The evaluation of family relatives of the index case for this mutation using PCR-RFLP analysis, identified two additional carriers in a three-generation family. Obesity, eating behavior and body composition phenotypes in this family revealed a possible relation of this variant with obesity in the presence of reduced penetrance. According to our knowledge, this is the first report of MC4R mutations in South American populations.
Assuntos
Comportamento Alimentar/fisiologia , Mutação de Sentido Incorreto/genética , Obesidade/genética , Receptor Tipo 4 de Melanocortina/genética , Adulto , Idoso , Composição Corporal/genética , Índice de Massa Corporal , Criança , Chile , Características da Família , Feminino , Frequência do Gene , Heterozigoto , Humanos , Isoleucina/genética , Masculino , Pessoa de Meia-Idade , Linhagem , Penetrância , Treonina/genéticaRESUMO
The aim of this study was to assess the frequency of fatty acid binding protein 2 (FABP2) Ala54Thr genetic polymorphism and to evaluate its association with obesity and insulin resistance in Chilean aboriginal populations. A sample of 96 urban Aymara and 111 urban Mapuche subjects aged 20-80 years were recruited for this cross-sectional study. Glucose, insulin and lipid profile were measured in fasting plasma samples. Insulin resistance was estimated through the HOMA-IR model. FABP2 Ala54Thr genotypes were determined by PCR followed by RFLP analysis. The allele frequency of Thr54 variant was estimated as 18.2% in Aymara subjects, which is one of the lowest reported to date. The corresponding frequency in Mapuche subjects was 31.9% (p<0.002). Regarding genotype-phenotype associations, no significant differences were found in any of the anthropometric or metabolic variables according to Ala54Thr genotypes. After adjustment by BMI and metabolic variables through a logistic regression analysis, the association of the FABP2 polymorphism with ethnic group persisted (Mapuche group: OR=2.37, 95% CI 1.319-4.277, p=0.004) It is unlikely that Ala54Thr polymorphism of the FABP2 gene plays a relevant role in obesity and insulin resistance in Chilean ethnic groups.
Assuntos
Proteínas de Ligação a Ácido Graxo/genética , Indígenas Sul-Americanos/genética , Resistência à Insulina/genética , Polimorfismo Genético , Substituição de Aminoácidos , Pressão Sanguínea , Chile , Jejum , Frequência do Gene , Genótipo , Humanos , Insulina/sangue , Razão de Chances , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Triglicerídeos/sangueRESUMO
BACKGROUND: It has been proposed that the toll-like receptor-4 gene (TLR4) may participate in the development of obesity and osteoporosis, in addition to its well-known role in the immune response. On the other hand, the adipose tissue of obese subjects shows an increased expression of the proinflammatory cytokine, tumour necrosis factor-alpha (TNF-alpha), which is released after lipopolysaccharide recognition by TLR4. AIM: To estimate the allele/genotype frequencies and linkage disequilibrium measures of Asp299Gly and Thr399Ile polymorphisms of the TLR4 gene in the Chilean elderly population, and to screen for their association with variables related to adiposity or bone mineral density. SUBJECTS AND METHODS: The study group included 227 unrelated Chilean elderly women (61-95 years) recruited from a population-based sample. Adiposity and bone mineral density measures were obtained using dual-energy X-ray absorptiometry. RESULTS: The allele frequencies for TNF -308A, TLR4 299Gly and TLR4 -399Ile were 9.3%, 4.6% and 4.4%, respectively, with Asp299Gly and Thr399Ile being in strong linkage disequilibrium (D' = 0.88). Although seriously restricted by the low frequency of the allele variants, no relevant association between genotypes and adiposity-related variables were found. Likewise, no significant association between osteoporosis status (categorized as osteoporosis, osteopenia or normal status) with TLR4 Asp299Gly or TNF -308G>A genotypes was found. CONCLUSION: It is unlikely that TLR4 Asp299Gly, TLR4 Thr399Ile or TNF -308G>A polymorphisms have a major influence on adiposity, bone mineral density or osteoporosis status in Chilean elderly women.
Assuntos
Adiposidade/genética , Densidade Óssea , Polimorfismo Genético , Receptor 4 Toll-Like/genética , Absorciometria de Fóton , Idoso , Idoso de 80 Anos ou mais , Pesos e Medidas Corporais , Chile , Feminino , Frequência do Gene , Humanos , Pessoa de Meia-IdadeRESUMO
OBJECTIVE: There are few studies on anthropometry and nutritional status in large and representative samples of elderly populations in Chile and South America. We describe age and sex differences in weight, height, body mass index, knee height, waist circumference, midarm circumference, triceps skinfold thickness, arm muscle area, and calf circumference in Chilean elderly subjects. METHODS: This was a population-based, cross-sectional study. A total of 1220 elderly persons (819 women and 411 men; age range, 60-99 y) were recruited in the city of Santiago (Chile) through a probabilistic sampling procedure carried out from October to December 1999. RESULTS: Men were significantly heavier and taller than women in all age groups, whereas body mass index values were significantly higher in women than in men. All anthropometric variables showed a decrease in average values with aging in men and women. The apparent negative slopes for the decline in average values of body weight with aging was of greater magnitude in women than in men (-0.42 kg/y and -0.54 kg/y in male and female subjects, respectively). However, significant age x sex interaction was detected only for triceps skinfold thickness. In women, quadratic terms for age provided a significantly better fit than did the simple linear model for the association between age and weight, body mass index, waist circumference, triceps skinfold thickness, calf circumference, or midarm circumference. CONCLUSION: These observations indicated that body weight changes associated with aging might be more severe in Chilean women than in men, probably determining a differential pattern of lean and fat mass loss.