Design and Verification of Integrated Circuitry for Real-Time Frailty Monitoring.

In this study, a new wireless electronic circuitry to analyze weight distribution was designed and incorporated into a chair to gather data related to common human postures (sitting and standing up). These common actions have a significant impact on various motor capabilities, including gait parameters, fall risk, and information on sarcopenia. The quality of these actions lacks an absolute measurement, and currently, there is no qualitative and objective metric for it. To address this, the designed analyzer introduces variables like Smoothness and Percussion to provide more information and objectify measurements in the assessment of stand-up/sit-down actions. Both the analyzer and the proposed variables offer additional information that can objectify assessments depending on the clinical eye of the physicians.

Early diagnosis of frailty: Technological and non-intrusive devices for clinical detection.

This work analyses different concepts for frailty diagnosis based on affordable standard technology such as smartphones or wearable devices. The goal is to provide ideas that go beyond classical diagnostic tools such as magnetic resonance imaging or tomography, thus changing the paradigm; enabling the detection of frailty without expensive facilities, in an ecological way for both patients and medical staff and even with continuous monitoring. Fried's five-point phenotype model of frailty along with a model based on trials and several classical physical tests were used for device classification. This work provides a starting point for future researchers who will have to try to bridge the gap separating elderly people from technology and medical tests in order to provide feasible, accurate and affordable tools for frailty monitoring for a wide range of users.

A Real-Time Clinical Decision Support System, for Mild Cognitive Impairment Detection, Based on a Hybrid Neural Architecture.

Clinical procedure for mild cognitive impairment (MCI) is mainly based on clinical records and short cognitive tests. However, low suspicion and difficulties in understanding test cut-offs make diagnostic accuracy being low, particularly in primary care. Artificial neural networks (ANNs) are suitable to design computed aided diagnostic systems because of their features of generating relationships between variables and their learning capability. The main aim pursued in that work is to explore the ability of a hybrid ANN-based system in order to provide a tool to assist in the clinical decision-making that facilitates a reliable MCI estimate. The model is designed to work with variables usually available in primary care, including Minimental Status Examination (MMSE), Functional Assessment Questionnaire (FAQ), Geriatric Depression Scale (GDS), age, and years of education. It will be useful in any clinical setting. Other important goal of our study is to compare the diagnostic rendering of ANN-based system and clinical physicians. A sample of 128 MCI subjects and 203 controls was selected from the Alzheimer's Disease Neuroimaging Initiative (ADNI). The ANN-based system found the optimal variable combination, being AUC, sensitivity, specificity, and clinical utility index (CUI) calculated. The ANN results were compared with those from medical experts which include two family physicians, a neurologist, and a geriatrician. The optimal ANN model reached an AUC of 95.2%, with a sensitivity of 90.0% and a specificity of 84.78% and was based on MMSE, FAQ, and age inputs. As a whole, physician performance achieved a sensitivity of 46.66% and a specificity of 91.3%. CUIs were also better for the ANN model. The proposed ANN system reaches excellent diagnostic accuracy although it is based only on common clinical tests. These results suggest that the system is especially suitable for primary care implementation, aiding physicians work with cognitive impairment suspicions.

Penfigoide y demencia / Pemphigoid and dementias

No disponible

Patrones de envejecimiento cerebral / Patterns of brain ageing

La neuroplasticidad otorga al cerebro gran capacidad adaptativa frente a transformaciones del medio que acontecen en el envejecimiento. En los modelos animales aparecen alteraciones en la neurotransmisión y desequilibrios en la expresión del factor de crecimiento neural. A nivel morfométrico, los cambios no son constantes. La pérdida de volumen se relaciona con alteraciones de la neuroplasticidad y afectación del neuropilo cerebral. Aunque no hay datos concluyentes, el ejercicio físico mejora los cambios moleculares, biológicos, funcionales y conductuales-cognitivos asociados al envejecimiento cerebral. En el cerebro humano envejecido se describe pérdida de peso y volumen y aumento del tamaño ventricular. No obstante, la neuroimagen muestra una variabilidad importante y muchos ancianos sanos no presentan cambios macroscópicos significativos. Respecto al número de neuronas, en la mayoría de las regiones cerebrales permanece estable a lo largo de la vida. La neuroplasticidad no se pierde con el envejecimiento, los cambios en la arborización dendrítica, la densidad de espinas y las sinapsis están más relacionados con la actividad cerebral que con la edad. A nivel molecular, a pesar de que la presencia de proteínas alteradas tau y b-amiloide se emplea como biomarcador de enfermedad neurodegenerativa, los estudios posmortem muestran que estas proteínas anómalas son frecuentes en los cerebros de personas ancianas sin demencia. Por último, debido a la relación entre enfermedades neurodegenerativas y alteraciones metabólicas, se analiza la influencia del factor de crecimiento insulínico y el envejecimiento, tanto a nivel de modelos animales como en la especie humana, y el posible efecto neuroprotector de la insulina (AU)

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and b-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the núbrains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin (AU)

[Patterns of brain ageing]. / Patrones de envejecimiento cerebral.

Neuroplasticity lends the brain a strong ability to adapt to changes in the environment that occur during ageing. Animal models have shown alterations in neurotransmission and imbalances in the expression of neural growth factor. Changes at the morphometric level are not constant. Volume loss is related to alterations in neuroplasticity and involvement of the cerebral neuropil. Although there are no conclusive data, physical exercise improves the molecular, biological, functional and behavioural-cognitive changes associated with brain ageing. The aged human brain has been described as showing weight and volume loss and increased ventricular size. However, neuroimaging shows significant variation and many healthy elderly individuals show no significant macroscopic changes. In most brain regions, the number of neurons remains stable throughout life. Neuroplasticity does not disappear with ageing, and changes in dendritic arborization and the density of spines and synapses are more closely related to brain activity than to age. At the molecular level, although the presence of altered Tau and ß-amyloid proteins is used as a biomarker of neurodegenerative disease, postmortem studies show that these abnormal proteins are common in the brains of elderly people without dementia. Finally, due to the relationship between neurodegenerative diseases and metabolic alterations, this article analyses the influence of insulin-like growth factor and ageing, both in animal models and in humans, and the possible neuroprotective effect of insulin.

[Inflammation and oxidation: predictive and/or causative factors]. / Inflamación y oxidación: factores predictivos y/o causales.

Brain ageing leads to a series of changes that reduce the processes of adaptation and response. These transformations can end in cognitive impairment and/or dementia. Although the cause of these changes is diverse, inflammation and oxidative stress explain some of the pathophysiological mechanisms of these anomalies of brain functioning. Neuroinflammation triggers neuronal injury through the presence of inflammatory cytokines and the activation of microglia through membrane receptors and nuclear activation factors. This neuroinflammatory phenomenon also affects neuron plasticity, altering the genesis and maintenance of long-term potentiation, leading to impairment of hippocampus-dependent memory. Oxidative stress and the production of free oxygen radicals also cause toxic effects in aged brains, largely due to lipid peroxidation and DNA damage. The identification of the molecular mechanisms involved in the pathogenesis of these events could shed new light on possible therapeutic targets and offer strategies for the prevention of diseases related to brain ageing, cognitive impairment and dementia.

Inflamación y oxidación: factores predictivos y/o causales / Inflammation and oxidation: predictive and/or causative factors

En el envejecimiento cerebral ocurren una serie de cambios que conllevan la disminución de los procesos de adaptación y respuesta. Estas transformaciones pueden finalizar en el padecimiento de deterioro cognitivo y/o demencia. Aunque el origen de estas modificaciones es diverso, la inflamación y el estrés oxidativo explican parte de los mecanismos fisiopatológicos de dichas anomalías del funcionamiento cerebral. La neuroinflamación desencadena daño a nivel neuronal mediante la presencia de citocinas inflamatorias y la activación de la microglía, a través de receptores de membrana y factores de activación nuclear. Este fenómeno neuroinflamatorio también afecta la plasticidad neuronal, alterando la génesis y el mantenimiento de la potenciación a largo plazo ocasionando deterioro en la memoria dependiente del hipocampo. El estrés oxidativo y la producción de radicales libres de oxígeno, también originan efectos tóxicos en los cerebros envejecidos, en gran parte debido a la peroxidación lipídica y daños en el ADN. La identificación de los mecanismos moleculares implicados en la patogénesis de estos sucesos puede arrojar nueva luz sobre posibles dianas terapéuticas y ofrecer estrategias para la prevención de las patologías relacionadas con el envejecimiento cerebral, el deterioro cognitivo y la demencia (AU)

Brain ageing leads to a series of changes that reduce the processes of adaptation and response. These transformations can end in cognitive impairment and/or dementia. Although the cause of these changes is diverse, inflammation and oxidative stress explain some of the pathophysiological mechanisms of these anomalies of brain functioning. Neuroinflammation triggers neuronal injury through the presence of inflammatory cytokines and the activation of microglia through membrane receptors and nuclear activation factors. This neuroinflammatory phenomenon also affects neuron plasticity, altering the genesis and maintenance of long-term potentiation, leading to impairment of hippocampus-dependent memory. Oxidative stress and the production of free oxygen radicals also cause toxic effects in aged brains, largely due to lipid peroxidation and DNA damage. The identification of the molecular mechanisms involved in the pathogenesis of these events could shed new light on possible therapeutic targets and offer strategies for the prevention of diseases related to brain ageing, cognitive impairment and dementia (AU)

Análisis longitudinal de parámetros nutricionales en una cohorte de ancianos con y sin demencia / Longitudinal analysis of nutrition parameters in a cohort of elderly people with and without dementia

Introducción. La evaluación nutricional longitudinal, debido a sus frecuentes alteraciones, es especialmente relevante en al anciano con deterioro cognitivo. El objetivo del presente estudio es valorar a lo largo del tiempo el efecto y la posible interacción del deterioro cognitivo y del envejecimiento en los parámetros nutricionales. Material y métodos. Estudio longitudinal prospectivo de 2 años de seguimiento en 301 ancianos (233 mujeres y 68 varones) en el medio residencial, 51 de los cuales tienen criterios de demencia. Los parámetros antropométricos y bioquímicos se obtuvieron según técnicas normalizadas. Resultados. Los ancianos con demencia presentan, en todos los parámetros estudiados, valores inferiores respecto a los ancianos sin demencia. En los pacientes con deterioro cognitivo los valores medios de los parámetros nutricionales permanecen estables y sin diferencias significativas tras 2 años de seguimiento: índice de masa corporal 24,5 ± 4,9 vs 24,2 ± 4,1; pliegue tricipital 15,0 ± 6,0 vs 14,7 ± 6,9; circunferencia braquial 25,9 ± 3,3 vs 25,7 ± 3,5, y albúmina 3,7 ± 0,3 vs 3,7 ± 0,3. En los pacientes sin deterioro cognitivo los valores al final del estudio han descendido respecto a los valores basales, excepto el pliegue bicipital y los triglicéridos. Conclusiones. Tras 2 años de seguimiento no se observa descenso de los parámetros nutricionales estudiados en los ancianos con demencia; sin embargo, sí aparece un descenso en los ancianos sin deterioro cognitivo. Las causas de estas diferencias pueden ser múltiples. Son necesarios más estudios, con mayor número de ancianos y un mayor periodo de seguimiento, para validar estos hallazgos (AU)

Introduction. It is important to assess longitudinal nutritional parameters during the ageing process in order to determine body composition changes. This procedure is more relevant when dealing with institutionalised geriatric patients suffering from cognitive impairment. The aim of this study was to assess the interactions, if any, between mental status and several nutritional parameters in a cohort of elderly people. Material and methods. A longitudinal prospective two years follow-up evaluation was performed on 301 elderly residents (233 females and 68 males) in a nursing home, of whom 51 of them fulfilled the clinical criteria for dementia. Both anthropometric and biochemical parameters were obtained annually, according to standard procedures. Results. The dementia group had lower values when compared to the non-dementia group. Furthermore, nutritional values remained constant in the group with cognitive impairment (no significant differences were observed throughout the study period). BMI 24.5 ± 4.9 vs 24.2 ± 4.1; tricipital skinfold 15.0 ± 6.0 vs 14.7 ± 6.9; brachial circumference 25.9 ± 3.3 vs 25.7 ± 3.5, and albumin 3.7 ± 0.3 vs 3.7 ± 0.3. At the end of the study, the group without cognitive impairment showed lower values in all the parameters analysed when compared to the baseline ones, except for bicipital fold and plasma triglycerides. Conclusions. Our study shows that there are no variations in the elderly with cognitive impairment, as regards the nutritional, anthropometric and biochemist parameters analysed. On the contrary, the group with normal cognitive status showed a reduction in most of the parameters. Further studies analysing larger populations of elderly people and over longer periods of time will provide more information to improve our knowledge on this important issue (AU)

[Longitudinal analysis of nutrition parameters in a cohort of elderly people with and without dementia]. / Análisis longitudinal de parámetros nutricionales en una cohorte de ancianos con y sin demencia.

INTRODUCTION: It is important to assess longitudinal nutritional parameters during the ageing process in order to determine body composition changes. This procedure is more relevant when dealing with institutionalised geriatric patients suffering from cognitive impairment. The aim of this study was to assess the interactions, if any, between mental status and several nutritional parameters in a cohort of elderly people. MATERIAL AND METHODS: A longitudinal prospective two years follow-up evaluation was performed on 301 elderly residents (233 females and 68 males) in a nursing home, of whom 51 of them fulfilled the clinical criteria for dementia. Both anthropometric and biochemical parameters were obtained annually, according to standard procedures. RESULTS: The dementia group had lower values when compared to the non-dementia group. Furthermore, nutritional values remained constant in the group with cognitive impairment (no significant differences were observed throughout the study period). BMI 24.5±4.9 vs 24.2±4.1; tricipital skinfold 15.0±6.0 vs 14.7±6.9; brachial circumference 25.9±3.3 vs 25.7±3.5, and albumin 3.7±0.3 vs 3.7±0.3. At the end of the study, the group without cognitive impairment showed lower values in all the parameters analysed when compared to the baseline ones, except for bicipital fold and plasma triglycerides. CONCLUSIONS: Our study shows that there are no variations in the elderly with cognitive impairment, as regards the nutritional, anthropometric and biochemist parameters analysed. On the contrary, the group with normal cognitive status showed a reduction in most of the parameters. Further studies analysing larger populations of elderly people and over longer periods of time will provide more information to improve our knowledge on this important issue.

Genética y enfermedad de Alzheimer: población en riesgo / Genetics and Alzheimer's disease: a population at risk

La elevada prevalencia de la enfermedad de Alzheimer (EA), junto con la posibilidad de nuevas pautas en el diagnóstico mediante el empleo de los biomarcadores está cambiando el enfoque de los ancianos con demencia o en riesgo de padecerla. En este sentido parece importante revisar los aspectos genéticos de los ancianos con EA familiar, así como los ancianos con riesgo de padecer EA. La amplia difusión de los estudios genéticos asociados a esta afección también puede ser de gran ayuda. Además de los genes del amiloide, las presenilinas y la apolipoproteína E, implicados en la patogenia de la EA, debemos añadir otros genes recientemente relacionados con la enfermedad entre los que destacan el gen de la clusterina y los de fosfatidil-inositol de unión a clatrina y el del receptor de la proteína del complemento C3b(AU)

The high prevalence of Alzheimer's disease, along with the possibility of new approaches in diagnosis through the use of biomarkers of cerebrospinal fluid is shifting the focus to the elderly with dementia or at risk. In this sense it seems important to review the genetic aspects of the elderly with familial Alzheimer's disease as well as those at risk. The wide distribution of genetic studies associated with this condition may also be helpful. To the classical findings of the genes for amyloid, the presenilins and apolipoprotein E, we must add other genes recently implicated in the pathogenesis of the disease, among which are found the clusterin gene, encoding the phosphatidyl-inositol-binding clathrin assembly protein gene, and the receptor for the complement C3b protein(AU)

[Genetics and Alzheimer's disease: a population at risk]. / Genética y enfermedad de Alzheimer: población en riesgo.

The high prevalence of Alzheimer's disease, along with the possibility of new approaches in diagnosis through the use of biomarkers of cerebrospinal fluid is shifting the focus to the elderly with dementia or at risk. In this sense it seems important to review the genetic aspects of the elderly with familial Alzheimer's disease as well as those at risk. The wide distribution of genetic studies associated with this condition may also be helpful. To the classical findings of the genes for amyloid, the presenilins and apolipoprotein E, we must add other genes recently implicated in the pathogenesis of the disease, among which are found the clusterin gene, encoding the phosphatidyl-inositol-binding clathrin assembly protein gene, and the receptor for the complement C3b protein.

[Stereology as a tool to estimate brain volume and cortical atrophy in elders with dementia]. / La estereología como herramienta de cuantificación del volumen y la atrofia cortical en el cerebro del anciano con demencia.

INTRODUCTION: stereology is a body of methods that allow unbiased and efficient estimation of geometric quantities defined in arbitrary physical structures. In particular, stereology is a valuable tool to assist neuroimaging in the estimation of morphometric parameters in the brain. Therefore, stereology may confer objectivity in the complementary and diagnostic evaluation of dementia by adding disease by adding quantitative data to clinical evaluation. OBJECTIVES AND METHODS: our purpose was to illustrate estimation of brain volume and pial surface area by means of quantitative, computer-assisted stereological methods. Both parameters were estimated by means of a vertical design with a single series of parallel Cavalieri sections at a random orientation and perpendicular to a fixed horizontal plane. The sections were obtained by magnetic resonance imaging. Suitable test systems (of test points for volume, and of cycloids for surface area) were superimposed on these sections with the aid of special software. RESULTS: to explore the statistical error of the volume estimator due to stereological sampling, 5 or 10 systematic sections were used in combination with two test point densities in a ratio of 1:4, so that the workload varied in the proportions 1:2:4:8. The four resulting estimators varied between 986 and 1120 cm(3). The surface area estimators varied between 1947 and 2096 cm(2), with workloads varying in the proportions of 1:2:2.3:4.6. CONCLUSIONS: stereology is a simple and efficient tool to obtain objective brain volume and surface area estimators that are unbiased by design and accurate at a modest cost. Thus the corresponding methods can effectively assist in diagnostic and follow-up evaluation of elders with dementia.

14-3-3 zeta and tau genes interactively decrease Alzheimer's disease risk.

Abnormal tau hyperphosphorylation has been suggested as being one of the central events in the development of neurofibrillary tangles, which are one of the characteristic neuropathological lesions found in Alzheimer's disease (AD) brains. 14-3-3 zeta protein is associated with tau in brain and stimulates tau phosphorylation. In a case-control study in 293 AD patients and 396 healthy controls, we examined whether the combined gene effects between 14-3-3 zeta (intron 4, rs 983583) polymorphism and tau (intron 9, rs 2471738) polymorphism might be responsible for susceptibility to AD. Subjects carrying both the 14-3-3 zeta (intron 4, rs 983583) AA and the tau (intron 9, rs 2471738) CC genotypes had a two and a half times lower risk of developing AD than subjects without these risk genotypes (OR = 0.4, 95% CI = 0.2-0.8, p = 0.016). Considering synergistic effects between polymorphisms in tau phosphorylation related genes may help in determining the risk profile for AD.

La estereología como herramienta de cuantificación del volumen y la atrofia cortical en el cerebro del anciano con demencia / Stereology as a tool to estimate brain volume and cortical atrophy in elders with dementia

Introducción: la estereología es un conjunto de métodos que permiten la estimación insesgada y eficiente de cantidades geométricas definidas en estructuras arbitrarias. En particular, es una herramienta útil en la cuantificación de parámetros morfométricos cerebrales en estudios de neuroimagen. Por tanto, la estereología puede aportar una mayor objetividad en la evaluación complementaria y diagnóstica de ancianos con demencia, añadiendo datos cuantitativos a la evaluación clínica. Objetivos y métodos: nuestro objetivo es ilustrar la estimación del volumen cerebral y el área superficial de la corteza cerebral de un paciente anciano mediante procedimientos estereológicos cuantitativos asistidos por ordenador. Para estimar ambos parámetros se utilizó un diseño vertical con una serie de secciones paralelas de Cavalieri con orientación aleatoria y perpendiculares a un plano horizontal fijo. Las secciones se obtuvieron mediante resonancia magnética nuclear. Sobre ellas se superpusieron sondas sistemáticas (de puntos para el volumen y de cicloides para la superficie) mediante un software especial. Resultados: con objeto de explorar la variabilidad del error estadístico de las estimaciones, se utilizaron 5 o 10 secciones sistemáticas combinadas con dos densidades de puntos de sonda en la relación 1:4, de tal manera que el trabajo invertido varió en la relación 1:2:4:8. Los cuatro estimadores obtenidos variaron entre 986 y 1.120 cm3. Por otra parte, para el área de la superficie pial los estimadores variaron entre 1.947 y 2.096 cm2, con cargas de trabajo variables en la relación 1:2:2.3:4.6. Conclusiones: la estereología es una herramienta sencilla y eficiente, capaz de proporcionar estimaciones objetivas, no sesgadas por diseño, del volumen y la superficie cerebral pial con un coste modesto. Ello puede contribuir a facilitar la evaluación diagnóstica, evolutiva y pronóstica de pacientes ancianos con demencia

Introduction: stereology is a body of methods that allow unbiased and efficient estimation of geometric quantities defined in arbitrary physical structures. In particular, stereology is a valuable tool to assist neuroimaging in the estimation of morphometric parameters in the brain. Therefore, stereology may confer objectivity in the complementary and diagnostic evaluation of dementia by adding disease by adding quantitative data to clinical evaluation. Objectives and methods: our purpose was to illustrate estimation of brain volume and pial surface area by means of quantitative, computer-assisted stereological methods. Both parameters were estimated by means of a vertical design with a single series of parallel Cavalieri sections at a random orientation and perpendicular to a fixed horizontal plane. The sections were obtained by magnetic resonance imaging. Suitable test systems (of test points for volume, and of cycloids for surface area) were superimposed on these sections with the aid of special software. Results: to explore the statistical error of the volume estimator due to stereological sampling, 5 or 10 systematic sections were used in combination with two test point densities in a ratio of 1:4, so that the workload varied in the proportions 1:2:4:8. The four resulting estimators varied between 986 and 1120 cm3. The surface area estimators varied between 1947 and 2096 cm2, with workloads varying in the proportions of 1:2:2.3:4.6. Conclusions: stereology is a simple and efficient tool to obtain objective brain volume and surface area estimators that are unbiased by design and accurate at a modest cost. Thus the corresponding methods can effectively assist in diagnostic and follow-up evaluation of elders with dementia (AU)

No association of genetic variants of liver X receptor-beta with Alzheimer's disease risk.

Apolipoprotein E (APOE) epsilon4 allele is the strongest hitherto known risk factor for sporadic Alzheimer's disease (AD). Liver X receptor-beta (LXRbeta) is a transcription factor that controls expression of genes involved in brain cholesterol metabolism, and one of the main LXRbeta targets is APOE. To evaluate the relationship between LXRbeta genetic variants and AD, independently or in concert with the APOE epsilon4 allele, we examined three LXRbeta polymorphisms located in introns 2 (rs 2695121), 5 (rs 1052533), and 7 (rs 1405655), in 414 Spanish AD patients and 447 controls. The current study does not demonstrate an association between LXRbeta genotypes or haplotypes and AD, neither in the total sample nor when the populations were stratified for the presence or absence of the APOE epsilon4 allele.

Envoltura nuclear, laminopatías y envejecimiento acelerado / Nuclear envelope, laminopathies and accelerated ageing

El síndrome de Hutchinson-Gilford es un síndrome progeroide que se caracteriza por un envejecimiento acelerado que comienza tempranamente en la infancia. El estudio de células de pacientes y el desarrollo de modelos animales (Zmpste24­/­, Zmpste24­/­Lmna+/­, LmnaLCO/LCO) que reproducen esta dolencia ha aportado nuevos conocimientos para entender las bases genéticas de esta enfermedad y así también profundizar en las del envejecimiento fisiológico. El fenotipo característico de este síndrome se debe a alteraciones en la lamina nuclear, estructura formada por un conjunto de filamentos intermedios (laminas A, B y C) que permiten mantener la organización de la envoltura nuclear. Se ha demostrado que una mutación del gen LMNA, que sintetiza la lamina A, es la del depósito de lamina A farnesilada (progerina) que es la causante de las alteraciones en la envoltura nuclear y del fenotipo de este raro síndrome. El empleo de moléculas que actúan sobre diferentes pasos en la síntesis de progerina se está revelando como un futuro terapéutico prometedor para revertir los efectos nocivos de su síntesis

Hutchinson-Gilford disease is a progeroid syndrome characterized by accelerated ageing beginning in early childhood. Study of several types of cells from patients with this syndrome and the development of animal models (Zmpste24­/­, Zmpste24­/­Lmna+/­, LmnaLCO/LCO) that mimic this disease have increased knowledge of the genetic foundations of this rare entity and those of normal ageing. The phenotypic features of this syndrome are caused by alterations in the fibrillar components of the nuclear lamina (lamins A, B, and C), which maintain the structure of the nuclear envelope. A point mutation in the gene for lamin A (LMNA) induces deposit of a farnesylated lamin A (progerin), which causes the nuclear alterations observed in the affected cells. The use of several molecules that interfere with progerin synthesis has been proposed as a promising potential therapeutic approach to reverse the adverse effects of progerin synthesis