Publicação
Centenários em Portugal : contribuição para o estudo de fatores genéticos e ambientais associados à longevidade
| Resumo: | Introduction: In Portugal, as in other regions of the world, the growing trend of the centenarian population and the existence of few studies justified the dedication to the theme. There are several explanatory theories of aging, some environmental, other genetic. With age there is a change in body composition and cognitive capacity. There is a consensus that high cardiovascular risk limits longevity. Objectives: This study aimed to characterize, in a sample of the centenarian population of Continental Portugal, both phenotypic (anthropometric, body composition, hemodynamic and biochemical), environmental aspects (place of residence in most of life, type of profession practiced and activities of caring and with some intellectual content, eating habits, alcoholic and smoking habits, use of medicines and medicinal plants, prayer practices, restful sleep), and genetic (polymorphisms associated with the aging process and cardiovascular risk), as well as identifying peculiarities of centenarian individuals; Comparing the parameters considered, between the sexes in the centenarians group and of these, with a control group composed of individuals of low and high cardiovascular risk of both sexes. Population and sample: After a long identification work, 253 centenarian individuals were selected, in the different regions of the country, with mean age ± SD of 100.26 ± 1.99 years, with the capacity to communicate, having been visited, interviewed and evaluated in their dwelling place. The control group consisted of 268 individuals, 67.51 ± 3.25 years old, 60.1% of high CV risk, selected in the Department of Heart and Vessels of Santa Maria Hospital and a Health Center of Lisbon. Methodology and procedures: The questionnaire was used as an instrument for collecting information and as a guide for the collection of objective evaluation data. The results of the laboratory tests provided were recorded. Samples of saliva were collected and transported in thermal bags for genetic analysis. They were used: Mini-Mental test; a semi-quantitative food frequency questionnaire aided by photographic models; Jaeger's card for visual evaluation; the whisper test for auditory evaluation; an anthropometric tape measure, a stadiometer, and a portable tetrapolar bioelectrical impedance apparatus for anthropometric evaluation and body composition; the timed up and go (TUG) test for evaluation of mobility and balance; an automatic blood pressure device. In the scope of the evaluation of health status (hypertension, diabetes, obesity, hypohydration, sarcopenia, osteoporosis, mobility, dyslipidemia), criteria were used, predefined by reference entities. Mean arterial pressure, pulse pressure, myocardial volume oxygen consumption, as well as body mass, fat mass, bone mass and muscle mass indices, LDL and non-HDL cholesterol were calculated and creatinine clearance were estimated. The fat mass was further calculated on the basis of the anthropometric equations of Deurenberg and Gallagher, and the resting metabolic rate by the Harris-Benedit equation and the results compared with the biompedance values using the Bland-Altman analysis. Cardiovascular risk was determined using the QRISK®2-2016 prediction algorithm. Eight genetic variants were studied in 6 polymorphic genes involved in oxidative stress and associated with cardiovascular risk and aging (Angiotensin Conversion Enzyme (ACE), rs4646994; Angiotensinogen (AGT), rs699 and rs4762; Angiotensin II Receptor 1 (AGTR1); G protein-coupled receptor kinase 4 (GRK4), rs2960306 and rs1024323; Solute Carrier Family 12 Member 3 (SLC12A3), rs13306673. Genotyping was performed using a DNA MicroChip in a high-throughput platform using iPlex MassARRAY® from Agena Bioscience technology, and the MALDI-TOF mass spectrometry reading. The frequency of genotypes and the balance of their proportions was estimated according to Hardy and Weinberg law. Statistics was performed using SPSS version 21, "Primer of Biostatistics" and MDR (Multifactor Dimensionality Reduction). The level of significance was established at alpha = 5 %. Results: The results indicate that centenarians in general have indicators that are more favorable to longevity than the control group. There was a higher prevalence of women among centenarians. The presence of indicators favoring longevity in the female sex is already observed at younger ages, especially in the control group. The results show that throughout life, there are a number of environmental factors that favor longevity: a quiet lifestyle, economic status with few deprivations, extended professional activity beyond retirement age, participation in voluntary caring activities, healthy and low-calorie eating habits, in which legumes and vegetables predominate, absence of smoking, spontaneous restorative sleep, regular prayer habits, and the rarity of life-threatening cardiovascular diseases are part of the profile of centenarians. Regarding the current state, this study found that centenarians are mostly (61.6 %), eutrophic (21.1 ± 3.68 kg / m2) and that hypertension is frequent among them (64.4 %), but of a slight and controlled degree, with better therapeutic response, not impeding longevity, in contrast to the results referring to the subgroup of high risk of the control group. The same was verified in relation to the blood glucose and cholesterol levels of serum LDL, therefore, a more favorable profile for longevity among centenarians. The anthropometric and bioimpedance indicators evaluated reinforce this profile, with BMI, body fat, visceral fat, waist circumference, waist / hip ratio and basal metabolism, which are low risk criteria, significantly different from those in the control group. The high frequency of sarcopenia and osteoporosis, particularly associated with low weight and leading to inadequate physical performance, suggests the need for adequate nutrition and the promotion of physical activity adjusted to the specific conditions of centenarians. Intense physical activity in the past seems to play a protective role for sarcopenia. As for osteoporosis, it is important to emphasize, besides the female sex, its presence among males, which can not be ignored. The existence of centenarian relatives may have some role in longevity, but not determinant. The DD ACE and GG NOS3 functional genotypic variants were more frequent in centenarians than in the control group suggesting that the polymorphisms of these enzymes are associated with cardiovascular risk and longevity. The angiotensinogen genes (rs4762) and the AT1 receptor of angiotensin II show a synergistic interaction in relation to the action of ACE and NOS3 in hypertension and its control, and this epistatic relationship can modulate the action of ACE and NOS3, thus contributing to a profile favorable to longevity. Functional genetic variants of the GRK4 enzyme may, in synergy with those of the angiotensinogen gene, also influence cardiovascular risk. This risk was the one that had the most weight in the reduction of the life expectancy, following the I / D polymorphisms of the ACE and G / T of the NOS3. However, since QRISK is a composite indicator based on predominantly non-genetic factors, it highlights the importance of environmental factors in their contribution to longevity. Conclusions: This work allowed accomplishing the defined objectives, identifying environmental and genetic factors associated with longevity and, in this way, to support preventative measures at an earlier age, enabling act on modifiable environmental factors aiming at the 100 years of age, leading to a long life dignified, with socio-economic, physical, mental and psychological well-being. |
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| Autores principais: | Oliveira, Alda |
| Assunto: | Idoso de 80 anos ou mais Genética Plantas medicinais Estilo de vida Longevidade Teses de doutoramento - 2018 |
| Ano: | 2018 |
| País: | Portugal |
| Tipo de documento: | tese de doutoramento |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | português |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Introduction: In Portugal, as in other regions of the world, the growing trend of the centenarian population and the existence of few studies justified the dedication to the theme. There are several explanatory theories of aging, some environmental, other genetic. With age there is a change in body composition and cognitive capacity. There is a consensus that high cardiovascular risk limits longevity. Objectives: This study aimed to characterize, in a sample of the centenarian population of Continental Portugal, both phenotypic (anthropometric, body composition, hemodynamic and biochemical), environmental aspects (place of residence in most of life, type of profession practiced and activities of caring and with some intellectual content, eating habits, alcoholic and smoking habits, use of medicines and medicinal plants, prayer practices, restful sleep), and genetic (polymorphisms associated with the aging process and cardiovascular risk), as well as identifying peculiarities of centenarian individuals; Comparing the parameters considered, between the sexes in the centenarians group and of these, with a control group composed of individuals of low and high cardiovascular risk of both sexes. Population and sample: After a long identification work, 253 centenarian individuals were selected, in the different regions of the country, with mean age ± SD of 100.26 ± 1.99 years, with the capacity to communicate, having been visited, interviewed and evaluated in their dwelling place. The control group consisted of 268 individuals, 67.51 ± 3.25 years old, 60.1% of high CV risk, selected in the Department of Heart and Vessels of Santa Maria Hospital and a Health Center of Lisbon. Methodology and procedures: The questionnaire was used as an instrument for collecting information and as a guide for the collection of objective evaluation data. The results of the laboratory tests provided were recorded. Samples of saliva were collected and transported in thermal bags for genetic analysis. They were used: Mini-Mental test; a semi-quantitative food frequency questionnaire aided by photographic models; Jaeger's card for visual evaluation; the whisper test for auditory evaluation; an anthropometric tape measure, a stadiometer, and a portable tetrapolar bioelectrical impedance apparatus for anthropometric evaluation and body composition; the timed up and go (TUG) test for evaluation of mobility and balance; an automatic blood pressure device. In the scope of the evaluation of health status (hypertension, diabetes, obesity, hypohydration, sarcopenia, osteoporosis, mobility, dyslipidemia), criteria were used, predefined by reference entities. Mean arterial pressure, pulse pressure, myocardial volume oxygen consumption, as well as body mass, fat mass, bone mass and muscle mass indices, LDL and non-HDL cholesterol were calculated and creatinine clearance were estimated. The fat mass was further calculated on the basis of the anthropometric equations of Deurenberg and Gallagher, and the resting metabolic rate by the Harris-Benedit equation and the results compared with the biompedance values using the Bland-Altman analysis. Cardiovascular risk was determined using the QRISK®2-2016 prediction algorithm. Eight genetic variants were studied in 6 polymorphic genes involved in oxidative stress and associated with cardiovascular risk and aging (Angiotensin Conversion Enzyme (ACE), rs4646994; Angiotensinogen (AGT), rs699 and rs4762; Angiotensin II Receptor 1 (AGTR1); G protein-coupled receptor kinase 4 (GRK4), rs2960306 and rs1024323; Solute Carrier Family 12 Member 3 (SLC12A3), rs13306673. Genotyping was performed using a DNA MicroChip in a high-throughput platform using iPlex MassARRAY® from Agena Bioscience technology, and the MALDI-TOF mass spectrometry reading. The frequency of genotypes and the balance of their proportions was estimated according to Hardy and Weinberg law. Statistics was performed using SPSS version 21, "Primer of Biostatistics" and MDR (Multifactor Dimensionality Reduction). The level of significance was established at alpha = 5 %. Results: The results indicate that centenarians in general have indicators that are more favorable to longevity than the control group. There was a higher prevalence of women among centenarians. The presence of indicators favoring longevity in the female sex is already observed at younger ages, especially in the control group. The results show that throughout life, there are a number of environmental factors that favor longevity: a quiet lifestyle, economic status with few deprivations, extended professional activity beyond retirement age, participation in voluntary caring activities, healthy and low-calorie eating habits, in which legumes and vegetables predominate, absence of smoking, spontaneous restorative sleep, regular prayer habits, and the rarity of life-threatening cardiovascular diseases are part of the profile of centenarians. Regarding the current state, this study found that centenarians are mostly (61.6 %), eutrophic (21.1 ± 3.68 kg / m2) and that hypertension is frequent among them (64.4 %), but of a slight and controlled degree, with better therapeutic response, not impeding longevity, in contrast to the results referring to the subgroup of high risk of the control group. The same was verified in relation to the blood glucose and cholesterol levels of serum LDL, therefore, a more favorable profile for longevity among centenarians. The anthropometric and bioimpedance indicators evaluated reinforce this profile, with BMI, body fat, visceral fat, waist circumference, waist / hip ratio and basal metabolism, which are low risk criteria, significantly different from those in the control group. The high frequency of sarcopenia and osteoporosis, particularly associated with low weight and leading to inadequate physical performance, suggests the need for adequate nutrition and the promotion of physical activity adjusted to the specific conditions of centenarians. Intense physical activity in the past seems to play a protective role for sarcopenia. As for osteoporosis, it is important to emphasize, besides the female sex, its presence among males, which can not be ignored. The existence of centenarian relatives may have some role in longevity, but not determinant. The DD ACE and GG NOS3 functional genotypic variants were more frequent in centenarians than in the control group suggesting that the polymorphisms of these enzymes are associated with cardiovascular risk and longevity. The angiotensinogen genes (rs4762) and the AT1 receptor of angiotensin II show a synergistic interaction in relation to the action of ACE and NOS3 in hypertension and its control, and this epistatic relationship can modulate the action of ACE and NOS3, thus contributing to a profile favorable to longevity. Functional genetic variants of the GRK4 enzyme may, in synergy with those of the angiotensinogen gene, also influence cardiovascular risk. This risk was the one that had the most weight in the reduction of the life expectancy, following the I / D polymorphisms of the ACE and G / T of the NOS3. However, since QRISK is a composite indicator based on predominantly non-genetic factors, it highlights the importance of environmental factors in their contribution to longevity. Conclusions: This work allowed accomplishing the defined objectives, identifying environmental and genetic factors associated with longevity and, in this way, to support preventative measures at an earlier age, enabling act on modifiable environmental factors aiming at the 100 years of age, leading to a long life dignified, with socio-economic, physical, mental and psychological well-being. |
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