Lipodystrophy as a target to delay premature aging.

Lipodystrophy syndromes are rare diseases characterized by low levels and an abnormal distribution of adipose tissue, caused by diverse genetic or acquired causes. These conditions commonly exhibit metabolic complications, including insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, and adipose tissue dysfunction. Moreover, genetic lipodystrophic laminopathies exhibit a premature aging phenotype, emphasizing the importance of restoring adipose tissue distribution and function. In this opinion, we discuss the relevance of adipose tissue reestablishment as a potential approach to alleviate premature aging and age-related complications in genetic lipodystrophy syndromes.

Impact of age, antiretroviral therapy, and cancer on epigenetic aging in people living with HIV.

BACKGROUND: Premature aging has been identified as a global risk factor for cancer. Causes of premature aging are multifactorial, including inflammation, infection, chronic stress, and lifestyle factors. METHOD: We evaluated whether premature aging in people living with HIV (PLWH) was associated with antiretroviral therapy (ART) or the diagnosis of cancer. We used well-established DNA methylation patterns to assess premature aging, using Horvath et al., in individuals with HIV located in Cleveland, Ohio and compared these to standardized datasets of US historical blood samples. Some of the PLWH developed cancer over time. RESULTS: We found that DNA methylation analysis identified accelerated aging in PLWH whereas ART therapy mitigated the advancement of DNA methylation age. A variety of cancers were observed in this population, but a cancer diagnosis was not significantly associated with more advanced DNA methylation age. CONCLUSION: We find that the age acceleration detected in PLWH is mitigated by ART therapy and is not further accelerated by a diagnosis of cancer.

ON RADIATION-INDUCED AGING: ACCELERATED OR PREMATURE AGING.

The concept of radiation-induced aging is revisited from the viewpoint of a mathematical model. The effect of radiation on carcinogenesis is treated based on the Armitage-Doll multi-stage theory. The formula obtained for cancer incidence rate indicates that radiation dose can be explained in terms of time. Radiation-induced aging for acute and chronic exposures is described using age-specific cancer incidence rates as a measure of aging. It shows that accelerated aging is related to the dose rate, whereas premature aging is related to the cumulative dose, providing a simple and natural interpretation of radiation-induced aging. The usefulness of this approach is demonstrated by applying the formula to cancer prevalence data from mice chronically exposed to low dose-rate radiation.

Síndrome de Werner: relato de caso / Werner's syndrome: case report / Síndrome de Werner: reporte de un caso

Introdução: Síndrome de Werner, doença autossômica recessiva, tem como característica o envelhecimento precoce e acelerado. Objetivo: Descrever a evolução clínica favorável da síndrome de Werner em paciente acompanhada periodicamente no ambulatório de geriatria para promover atenção ao processo de envelhecimento por meio de abordagem preventiva e tratamento precoce das alterações que caracterizam a doença. Material e Método: Paciente de 31 anos de idade, sexo feminino, admitida no ambulatório de Aconselhamento Genético de um hospital-escola do noroeste paulista, apresentando baixa estatura, ulcerações, dor em região plantar e dificuldade para deambular, alterações cutâneas pigmentares com fissuras e ressecamento de toda a pele, além de cabelos grisalhos e quebradiços, catarata bilateral, hipotireoidismo e osteoporose. Tinha antecedentes familiares compatíveis com pais consanguíneos, um casal de irmãos hígidos e mãe com histórico de ocorrência de dois abortos espontâneos consecutivos. Apresentava, portanto, critérios diagnósticos para síndrome de Werner. Foi tratada nos ambulatórios de geriatria, endocrinologia, dermatologia, oftalmologia e ortopedia da mesma Instituição. Resultado: O tratamento consistiu na remoção cirúrgica de catarata, uso de levotiroxina 75 mcg/dia e de creme hidratante para pele (ácido salicílico 20% e vaselina sólida 30g), calçado ortopédico para pé neuropático com solado em EVA de média compressão, antiderrapante, confeccionado sob medida. Houve melhora na sintomatologia, especialmente quanto à deambulação com as medidas terapêuticas adotadas. Conclusão: A avaliação interdisciplinar inicial da paciente foi fundamental, pois possibilitou a elaboração precoce do diagnóstico e o acompanhamento no ambulatório de geriatria, promovendo maior atenção ao processo de envelhecimento preconizado por uma abordagem preventiva e tratamento subsequente das alterações que caracterizam a síndrome de Werner.(AU)

Introduction: Werner syndrome, an autosomal recessive disease, is characterized by premature and accelerated aging. Objective: To describe the favorable clinical evolution of Werner's syndrome in a patient periodically followed in the geriatric outpatient clinic to promote attention to the aging process through a preventive approach and early treatment of the changes that characterize the disease. Material and Method: A 31-year-old female patient, admitted to the Genetic Counseling outpatient clinic of a school hospital in northwestern pigmentary skin changes with cracks and dryness of the entire skin, as well as gray and brittle hair, bilateral cataract, hypothyroidism and osteoporosis. She had a family history compatible with consanguineous parents, a couple of healthy siblings and a mother with a history of two consecutive miscarriages. It therefore presented diagnostic criteria for Werner syndrome. She was treated in geriatric, endocrinology, dermatology, ophthalmology and orthopedics clinics of the same institution. Result: The treatment consisted of surgical removal of cataract, use of levothyroxine 75 mcg/day and moisturizing cream for skin (salicylic acid 20% and solid petroleum jelly 30g), orthopedic footwear for neuropathic foot anti-slip, made to measure. There was improvement in symptomatology, especially regarding ambulation with the therapeutic measures adopted. Conclusion: The initial interdisciplinary evaluation of the patient was fundamental, since it enabled the early preparation of the diagnosis and the follow-up in the geriatric outpatient clinic, promoting greater attention to the aging process recommended by a preventive approach and subsequent treatment of the changes that characterize Werner's syndrome.(AU)

Introducción: El síndrome de Werner, una enfermedad autosómica recesiva, se caracteriza por un envejecimiento prematuro y acelerado. Objetivo: Describir la evolución clínica favorable del síndrome de Werner en un paciente en seguimiento periódico en la consulta externa de geriatría para promover la atención al proceso de envejecimiento a través de un abordaje...(AU)

Skin Abnormalities in Disorders with DNA Repair Defects, Premature Aging, and Mitochondrial Dysfunction.

Defects in DNA repair pathways and alterations of mitochondrial energy metabolism have been reported in multiple skin disorders. More than 10% of patients with primary mitochondrial dysfunction exhibit dermatological features including rashes and hair and pigmentation abnormalities. Accumulation of oxidative DNA damage and dysfunctional mitochondria affect cellular homeostasis leading to increased apoptosis. Emerging evidence demonstrates that genetic disorders of premature aging that alter DNA repair pathways and cause mitochondrial dysfunction, such as Rothmund-Thomson syndrome, Werner syndrome, and Cockayne syndrome, also exhibit skin disease. This article summarizes recent advances in the research pertaining to these syndromes and molecular mechanisms underlying their skin pathologies.

Chronic Obstructive Pulmonary Disease as a Main Factor of Premature Aging.

(1) Background: Chronic obstructive pulmonary disease (COPD) is defined as an inflammatory disorder that presents an increasingly prevalent health problem. Accelerated aging has been examined as a pathologic mechanism of many chronic diseases like COPD. We examined whether COPD is combined with accelerated aging, studying two hormones, dehydroepiandrosterone (DHEA) and growth hormone (GH), known to be characteristic biological markers of aging. (2) Methods: Data were collected from 119 participants, 70 (58.8%) COPD patients and 49 (41.2%) from a health control group over the period of 2014⁻2016 in a spirometry program. Information about their medical history, tobacco use, and blood tests was obtained. (3) Results: The average age of the health control patients was 73.5 years (SD = 5.5), and that of the COPD patients was 75.4 years (SD = 6.9). Both groups were similar in age and sex. A greater proportion of smokers were found in the COPD group (87.1%) versus the control group (36.7%). The majority of COPD patients were classified as STAGE II (51.4%) and STAGE III (37.1%) according to GOLD (Global Initiative for Chronic Obstructive Pulmonary Disease). Levels of DHEA (SD = 17.1) and GH (SD = 0.37) were significantly lower in the COPD group (p < 0.001) compared to those in the controls (SD = 26.3, SD = 0.79). DHEA and GH were more significant and negatively correlated with age. The regression equation of DHEA with age produced a coefficient equal to 1.26. In this study, the difference in DHEA between COPD patients and controls was, on average, 30.2 µg/dL, indicating that the biological age of a COPD patient is on average about 24 years older than that of a control subject of the same age. Similarly, the difference in GH between COPD patients and controls was, on average, 0.42 ng/mL, indicating that the biological age of a COPD patient is on average about 13.1 years older than that of a control subject of the same age. (4) Conclusions: The findings of our study strongly suggest the presence of premature biological aging in COPD patients. Their biological age could actually vary from 13 to 23 years older than non-COPD controls according to DHEA and GH variation.

Bone mineral density from early to middle adulthood in persons with Down syndrome.

BACKGROUND: While accelerated ageing is recognised among individuals with Down syndrome (DS), the trajectory of their bone health across adulthood remains poorly understood. METHODS: This study aimed to determine the age-related loss of bone mineral density (BMD) of the lumbar spine in 128 adults with DS aged 18 to 54 years compared with 723 counterparts without DS. RESULTS: Men and women with DS had lower level of BMD than counterparts without DS across age groups. Magnitude of decrement in BMD as reflected in the z-scores was similar between younger and older men with DS. Older women with DS, on the contrary, showed greater decrement in older ages especially in their fourth decade of life. Osteopenia and osteoporosis as defined using age-specific and gender-specific T-scores affected greater number of men with DS (38% and 25%) than women (17% and 17%) aged 40-49 years. CONCLUSIONS: Findings supported adults with DS, especially men, to have early bone mineral testing.

Mood Disorders, Accelerated Aging, and Inflammation: Is the Link Hidden in Telomeres?

Mood disorders are associated with an increased risk of aging-related diseases, which greatly contribute to the excess morbidity and mortality observed in affected individuals. Clinical and molecular findings also suggest that mood disorders might be characterized by a permanent state of low-grade inflammation. At the cellular level, aging translates into telomeres shortening. Intriguingly, inflammation and telomere shortening show a bidirectional association: a pro-inflammatory state seems to contribute to aging and telomere dysfunction, and telomere attrition is able to induce low-grade inflammation. Several independent studies have reported shorter telomere length and increased levels of circulating inflammatory cytokines in mood disorders, suggesting a complex interplay between altered inflammatory⁻immune responses and telomere dynamics in the etiopathogenesis of these disorders. In this review, we critically discuss studies investigating the role of telomere attrition and inflammation in the pathogenesis and course of mood disorders, and in pharmacological treatments with psychotropic medications.

Premature placental aging in term small-for-gestational-age and growth-restricted fetuses.

OBJECTIVE: To perform a comprehensive assessment of the placental aging process in small term fetuses classified as being small-for-gestational age (SGA) or having fetal growth restriction (FGR) through analysis of senescence and apoptosis markers. METHODS: This was a prospective nested case-control study of singleton pregnancies delivered at term, including 21 control pregnancies with normally grown fetuses and 36 with a small fetus classified as SGA (birth weight between the 3rd and 9th percentiles and normal fetoplacental Doppler; n = 18) or FGR (birth weight < 3rd percentile and/or abnormal cerebroplacental ratio and/or uterine artery Doppler; n = 18). Telomerase activity, telomere length (quantified by comparing the amount of amplification product for the telomere sequence (T) to that of a single copy of the gene 36B4 (S)) and RNA expression of senescence (Sirtuins 1, 3 and 6) and apoptosis (p53, p21, BAX and Caspases 3 and 9) markers (analyzed using the 2-ΔΔCt method) were determined in placental samples collected at birth and compared between the three groups. RESULTS: Compared to pregnancies with a normally grown fetus, both SGA and FGR pregnancies presented signs of accelerated placental aging, including lower telomerase activity (mean ± SD, 12.8 ± 6.6% in controls vs 7.98 ± 4.2% in SGA vs 7.79 ± 4.6% in FGR; P = 0.008), shorter telomeres (mean ± SD T/S ratio, 1.20 ± 0.6 in controls vs 1.08 ± 0.9 in SGA vs 0.66 ± 0.5 in FGR; P = 0.047) and reduced Sirtuin-1 RNA expression (mean ± SD 2-ΔΔCt , 1.55 ± 0.8 in controls vs 0.91 ± 0.8 in SGA vs 0.63 ± 0.5 in FGR; P = 0.001) together with increased p53 RNA expression (median (interquartile range) 2-ΔΔCt , 1.07 (0.3-3.3) in controls vs 5.39 (0.6-15) in SGA vs 3.75 (0.9-7.8) in FGR; P = 0.040). FGR cases presented signs of apoptosis, with increased Caspase-3 RNA levels (median (interquartile range) 2-ΔΔCt , 0.94 (0.7-1.7) in controls vs 3.98 (0.9-31) in FGR; P = 0.031) and Caspase-9 RNA levels (median (interquartile range) 2-ΔΔCt , 1.21 (0.6-4.0) in controls vs 3.87 (1.5-9.0) in FGR; P = 0.037) compared with controls. In addition, Sirtuin-1 RNA expression, telomerase activity, telomere length and Caspase-3 activity showed significant linear trends across groups as severity of the condition increased. CONCLUSIONS: Accelerated placental aging was observed in both clinical forms of late-onset fetal smallness (SGA and FGR), supporting a common pathophysiology and challenging the concept of SGA fetuses being constitutionally small. Copyright © 2018 ISUOG. Published by John Wiley & Sons Ltd.

Envejecimiento prematuro de la placenta en fetos pequeños para la edad gestacional y con restricción del crecimiento OBJETIVO: Realizar una evaluación integral del proceso de envejecimiento de la placenta en fetos a término clasificados como pequeños para la edad gestacional (PEG) o con restricción del crecimiento fetal (RCF) mediante el análisis de los marcadores de senescencia y apoptosis. MÉTODOS: Este fue un estudio prospectivo de casos y controles anidados de embarazos únicos a término, que incluyó 21 embarazos de control con fetos de crecimiento normal y 36 con un feto clasificado como PEG (peso al nacer entre los percentiles 3o y 9o y Doppler fetoplacentario normal; n=18) o con RCF (peso al nacer menor del percentil 3o y/o relación cerebroplacentaria anómala y/o Doppler de la arteria uterina; n=18). La actividad de la telomerasa, la longitud de los telómeros (cuantificada comparando la cantidad de producto de amplificación para la secuencia de telómeros (T) con la de una sola copia del gen 36B4 (S)) y la expresión del ARN de la senescencia (Sirtuinas 1, 3 y 6) y los marcadores de apoptosis (p53, p21, BAX y Caspasas 3 y 9) (analizados usando el método 2-∆∆Ct ) se determinaron en muestras de placenta obtenidas en el momento del nacimiento y se compararon entre los tres grupos. RESULTADOS: En comparación con los embarazos con un feto de crecimiento normal, tanto los embarazos PEG y con RCF presentaron signos de envejecimiento placentario acelerado, como una menor actividad de la telomerasa (media ± SD, 12,8 ± 6,6% en los controles frente a 7,98 ± 4,2% en PEG frente a 7,79 ± 4,6% en RCF; P=0,008), telómeros más cortos (media ± SD razón T/S, 1,20 ± 0,6 en los controles frente a 1,08 ± 0,9 en PEG frente a 0,66 ± 0,5 en RCF; P=0,047) y expresión reducida de la Sirtuina 1 en el ARN (media ± SD 2-∆∆Ct , 1,55 ± 0,8 en los controles frente a 0,91 ± 0,8 en PEG frente a 0,63 ± 0,5 en RCF; P=0,001), junto con una mayor expresión del p53 en el ARN (mediana (rango intercuartil) 2-∆∆Ct , 1,07 (0,3-3,3) en los controles frente a 5,39 (0,6-15) en PEG frente a 3,75 (0,9-7,8) en RCF; P=0,040). Los casos de RCF presentaron signos de apoptosis, con un aumento de los niveles en ARN de la Caspasa 3 (mediana (rango intercuartil) 2-∆∆Ct , 0,94 (0,7-1,7) en los controles frente a 3,98 (0,9-31) en RCF; P=0,031) y Caspasa 9 (mediana (rango intercuartil) 2-∆∆Ct , 1,21 (0,6-4,0) en los controles frente a 3,87 (1,5-9,0) en RCF; P=0,037) en comparación con los controles. Además, la expresión de la Sirtuina 1 en el ARN, la actividad de la telomerasa, la longitud de los telómeros y la actividad de la Caspasa 3 mostraron tendencias lineales significativas entre los grupos en función del aumento de la severidad de la anomalía. CONCLUSIONES: Se observó un envejecimiento acelerado de la placenta en ambas formas clínicas de tamaño pequeño del feto de inicio tardío (PEG y RCF), lo que apoya una fisiopatología común y pone en tela de juicio el concepto de que los fetos PEG son en pequeños por su propia condición.

Accelerated and Premature Aging Characterizing Regional Cortical Volume Loss in Human Immunodeficiency Virus Infection: Contributions From Alcohol, Substance Use, and Hepatitis C Coinfection.

BACKGROUND: Life expectancy of successfully treated human immunodeficiency virus (HIV)-infected individuals is approaching normal longevity. The growing HIV population ≥50 years of age is now at risk of developing HIV-associated neurocognitive disorder, acquiring coinfection with the hepatitis C virus (HCV), and engaging in hazardous drinking or drug consumption that can adversely affect trajectories of the healthy aging of brain structures. METHODS: This cross-sectional/longitudinal study quantified regional brain volumes from 1101 magnetic resonance imaging scans collected over 14 years in 549 participants (25 to 75 years of age): 68 HIV-infected individuals without alcohol dependence, 60 HIV-infected individuals with alcohol dependence, 222 alcohol-dependent individuals, and 199 control subjects. We tested 1) whether localized brain regions in HIV-infected individuals exhibited accelerated aging, or alternatively, nonaccelerated premature aging deficits; and 2) the extent to which alcohol or substance dependence or HCV coinfection altered brain aging trajectories. RESULTS: The HIV-infected cohort exhibited steeper declining volume trajectories than control subjects, consistently in the frontal cortex. Nonaccelerated volume deficits occurred in the temporal, parietal, insular, and cingulate regions of all three diagnostic groups. Alcohol and drug dependence comorbidities and HCV coinfection exacerbated HIV-related volume deficits. Accelerated age interactions in frontal and posterior parietal volumes endured in HIV-infected individuals free of alcohol or substance dependence and HCV infection comorbidities. Functionally, poorer HIV-associated neurocognitive disorder scores and Veterans Aging Cohort Study indices correlated with smaller regional brain volumes in the HIV-infected individuals without alcohol dependence and alcohol-dependent groups. CONCLUSIONS: HIV infection itself may confer a heightened risk of accelerated brain aging, potentially exacerbated by HCV coinfection and substance dependency. Confirmation would require a prospective study with a preinfection baseline.

Reduction of Premature Aging Markers After Gastric Bypass Surgery in Morbidly Obese Patients.

BACKGROUND: Obesity is considered to be a major comorbidity. Obese patients suffer from an increased proinflammatory state associated with a premature aging phenotype including increased secretion of senescence-associated secretory proteins (SASP) and reduced telomere length. Micro-ribonucleic acids (miRNAs) are non-coding RNA molecules that could modify the post-transcriptional process. Several studies have reported associations between miRNAs and metabolic unhealthy conditions. AIM: To determine if bariatric surgery and the resulting weight loss could reverse the premature aging phenotype. METHODS: We enrolled 58 morbidly obese patients undergoing bariatric surgery. Markers of premature aging including the SASP IL-6, CRP and PAI-1, 7 miRNAs, as well as telomere length and telomere oxidation in mononuclear cells were evaluated. RESULTS: Patients showed a significant drop of body mass index (BMI; 43.98 ± 3.5 versus 28.02 ± 4.1, p < 0.001). We observed a significant reduction in SASP including a reduction of 55% of plasma IL-6 levels (p = 0 < 0.001), 83% of CRP levels (p = 0.001) and 15% of plasma PAI-1 levels (p < 0.001). Telomere length doubled in the patient cohort (p < 0.001) and was accompanied by a reduction in the telomere oxidation index by 70% (p < 0.001). Telomere length was inversely correlated with telomere oxidation. The aging-associated miRNA miR10a_5p was upregulated significantly (p = 0.039), while the other tested miRNAs showed no difference. CONCLUSION: Our data indicate a significant reduction of the proinflammatory SASP after bariatric surgery. We observed an increase in telomere length and reduced oxidative stress at telomeres. miR10a_5p which is downregulated during aging was upregulated after surgery. Overall, bariatric surgery ameliorated the premature aging phenotype.

Effects of Bushen-Yizhi formula on age-related inflammation and oxidative stress in senescence-accelerated mice.

The present study aimed to investigate the possible effects and underlying molecular mechanism of Bushen­Yizhi formula (BSYZ), a traditional Chinese medicine, on age­related degeneration of brain physiology in senescence­accelerated mouse prone 8 (SAMP8) mice. SAMP8 mice (age, 6 months) were administered BSYZ (1.46, 2.92 and 5.84 g/kg/day) for 30 days. Morris water maze and step­down tests demonstrated that BSYZ significantly improved memory impairments in SAMP8 mice. In addition, BSYZ significantly enhanced the expression levels of peroxisome proliferator­activated receptor­Î³ and B­cell lymphoma extra­large, and downregulated the expression levels of inflammatory mediators, glial fibrillary acidic protein, cyclooxygenase­2, nuclear factor­κB and interleukin­1ß in the brain compared with untreated SAMP8 mice. Furthermore, BSYZ reversed disordered superoxide dismutase activity, malondialdehyde content and glutathione peroxidase activity, and ameliorated apoptosis and histological alterations. The present study indicated that BSYZ may attenuate cognitive impairment in SAMP8 mice, and modulate inflammation, oxidative stress and neuronal apoptosis. These results suggested that BSYZ may have the potential to be further developed into a therapeutic agent for protection against age­related neurodegenerative diseases.

The Processing-Speed Impairment in Psychosis Is More Than Just Accelerated Aging.

Processing speed is impaired in patients with psychosis, and deteriorates as a function of normal aging. These observations, in combination with other lines of research, suggest that psychosis may be a syndrome of accelerated aging. But do patients with psychosis perform poorly on tasks of processing speed for the same reasons as older adults? Fifty-one patients with psychotic illnesses and 90 controls with similar mean IQ (aged 19-69 years, all African American) completed a computerized processing-speed task, reminiscent of the classic digit-symbol coding task. The data were analyzed using the drift-diffusion model (DDM), and Bayesian inference was used to determine whether psychosis and aging had similar or divergent effects on the DDM parameters. Psychosis and aging were both associated with poor performance, but had divergent effects on the DDM parameters. Patients had lower information-processing efficiency ("drift rate") and longer nondecision time than controls, and psychosis per se did not influence response caution. By contrast, the primary effect of aging was to increase response caution, and had inconsistent effects on drift rate and nondecision time across patients and controls. The results reveal that psychosis and aging influenced performance in different ways, suggesting that the processing-speed impairment in psychosis is more than just accelerated aging. This study also demonstrates the potential utility of computational models and Bayesian inference for finely mapping the contributions of cognitive functions on simple neurocognitive tests.

Early declines in physical function among aging adults with type 2 diabetes.

AIMS: Type 2 diabetes (T2DM) is associated with reduced physical function and early disability. We hypothesized that changes in physical function occur early and differ by age. Our aims were to determine and compare differences in and predictors of physical function in older and younger adults with T2DM. METHODS: Eighty adults completed six-minute walk distance (6MWD) tests, wore wrist actigraphy for 5days and completed diabetes health and symptom surveys. Comparative and bivariate analyses were completed to assess differences between age groups determined by serial Box's M-plot analyses. RESULTS: 6MWD was low (476.9±106.2m), and negatively associated with female gender, age, neuropathic pain, diabetes duration, BMI, poor sleep quality, and fatigue and positively with habitual activity and education (p<0.05). Covariance matrices changed at age 59. In subjects age <58, 6MWD was predicted by gender, sleep quality, and neuropathic pain (R2=0.593, p<0.001). In those age ≥59, 6MWD was predicted by diabetes duration, education, and habitual activity (R2=0.554, p<0.001). There were no shared predictors of 6MWD between groups. CONCLUSIONS: T2DM is associated with early declines in physical function; the predictors of which change in midlife. Therapies to maintain or improve physical function should be tailored by age, pain symptoms, and habitual activity levels.

Envejecimiento e influencia de la inversión del cociente CD4/CD8 en la incidencia de las comorbilidades y mortalidad de una cohorte de pacientes infectados por el virus de inmunodeficiencia humana / Aging and influence of inversion of the CD4: CD8 ratio in the incidence of co-morbidities and mortality in a cohort of patients infected with human immunodeficiency virus

Fundamentos y objetivo. La inversión del cociente CD4/CD8 como indicador de inmunosenescencia puede ser un factor que permita anunciar el riesgo de presentar comorbilidades. Estudiamos la influencia del envejecimiento y de la inversión del cociente CD4/CD8 en la incidencia de comorbilidades y de mortalidad en la cohorte del Hospital Severo Ochoa. Métodos: Analizamos las diferencias en las tasas de incidencia de las comorbilidades ajustadas por la edad y evaluamos la inversión del cociente CD4/CD8 como factor de riesgo para la mortalidad y para el desarrollo de comorbilidades. Resultados: La edad se asoció a un incremento en la tasa de incidencia de diabetes mellitus, fracturas, EPOC y neoplasias no asociadas a sida. Encontramos un mayor riesgo de la tasa de incidencia de episodios clínicos no asociados a sida (OR 2,25; IC 95% 1,025-4,94) y episodios asociados a sida (OR 3,48; IC 95% 1,58-7,64) en los individuos con el cociente CD4/CD8 < 0,7. También los pacientes con un cociente CD4/CD8 < 0,7 presentaron una mayor riesgo de mortalidad (OR 5,96; IC 95% 0,73-48,40). Conclusión: Es importante detectar y prevenir comorbilidades no asociadas a sida en presencia del cociente CD4/CD8 < 0,7 (AU)

Background and objective: It has been postulated that the inversion of the CD4:CD8 ratio as a hallmark of immunosenescence can be an independent factor that can herald the risk of co-morbidities. We studied the influence of aging and inversion of the CD4:CD8 ratio in the incidence of comorbidities and mortality in the cohort of Hosptital Severo Ochoa. Methods: We analyzed the differences in the incidence rates of age-adjusted morbidities and evaluated the inversion of the CD4:CD8 ratio as predictor of mortality and development of comorbidities. Results: Age was associated with an increased incidence rate of diabetes mellitus, fractures, COPD and non-AIDS malignancies. We found an increased incidence rate of non-AIDS clinical events (OR 2.25; 95% CI 1.025-4.94) and AIDS events (OR 3.48; 95% CI 1.58-7.64) in individuals with CD4:CD8 ratio < 0.7. Moreover, patients with a CD4:CD8 ratio < 0.7 ratio had a higher risk of mortality (OR 5.96; 95% CI 0.73 to 48.40). Conclusion: It is important to detect and prevent non-AIDS comorbidities in the presence of a CD4:CD8 ratio < 0.7 (AU)

Primary hypertension is a disease of premature vascular aging associated with neuro-immuno-metabolic abnormalities.

There is an increasing amount of data indicating that primary hypertension (PH) is not only a hemodynamic phenomenon but also a complex syndrome involving abnormal fat tissue distribution, over-activity of the sympathetic nervous system (SNS), metabolic abnormalities, and activation of the immune system. In children, PH usually presents with a typical phenotype of disturbed body composition, accelerated biological maturity, and subtle immunological and metabolic abnormalities. This stage of the disease is potentially reversible. However, long-lasting over-activity of the SNS and immuno-metabolic alterations usually lead to an irreversible stage of cardiovascular disease. We describe an intermediate phenotype of children with PH, showing that PH is associated with accelerated development, i.e., early premature aging of the immune, metabolic, and vascular systems. The associations and determinants of hypertensive organ damage, the principles of treatment, and the possibility of rejuvenation of the cardiovascular system are discussed.

Fisiopatología del envejecimiento prematuro en los pacientes con infección por el VIH / No disponible

Tras 30 años de epidemia de la infección por el VIH muchos pacientes infectados han sobrevivido hasta edades más avanzadas tras la introducción del tratamiento antirretroviral de gran eficacia (TAR) en 1996. De 2000 a 2004, los CDC informaron que el número de adultos ≥ 50 años de edad que viven con infección por VIH y / o SIDA se duplicó. Además se espera que el número de personas mayores con VIH / SIDA aumente aún más durante la próxima década. Se estima que para el año 2020, más de la mitad de todos los individuos infectados por el VIH en los Estados Unidos sean mayores de 50 años. in embargo este aumento de la población VIH mayor de 50 años conlleva a una mayor prevalencia de determinadas comorbilidades relacionadas con la edad que en la población general aparecen en personas más mayores. Por tanto, el éxito que supone haber conseguido una mayor supervivencia no es tal si esto refleja un envejecimiento prematuro asociado a la infección por el VIH que está asociado principalmente a un proceso de inmunoactivación e inflamación crónica (AU)

No disponible

Características particulares en el medio penitenciario del envejecimiento de los internos infectados por el VIH / No disponible

La progresiva disminución de la mortalidad asociada a la infección por el VIH-1, y la consecuente cronificación de la enfermedad, está provocando un envejecimiento de la población infectada cuya repercusión en el medio penitenciario no es bien conocida. Existe una tendencia hacia el envejecimiento del conjunto de internos en centros penitenciarios españoles, y posiblemente esto también está ocurriendo entre los infectados por el VIH-1. Al analizar en un centro penitenciario la posible influencia del envejecimiento en la prevalencia de comorbilidades en pacientes infectados, se aprecia un significativo aumento de patologías médicas crónicas en los mayores de 50 años. Sería necesario confirmar estos datos en estudios más amplios para poder planificar en caso necesario estrategias de control de estas enfermedades concomitantes (AU)

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Premature aging in chronic kidney disease and chronic obstructive pulmonary disease: similarities and differences.

PURPOSE OF REVIEW: There is increasing clinical and pathophysiological evidence that a premature aging process is involved in the pathogenesis of systemic complications of many chronic organ diseases, which result in analogous phenotypes, including premature vascular aging, osteoporosis and muscle wasting. Novel developments from research into the aging process will, therefore, have relevance for understanding complications of organ diseases, such as chronic kidney disease and chronic obstructive pulmonary disease. The aim of the present article is to combine recent literature on aging mechanisms with evidence on the pathogenesis of systemic complications of these two chronic debilitating disorders. RECENT FINDINGS: Recently, nine hallmarks of aging have been identified. In this review, we argue that all of these hallmarks are relevant for the pathogenesis of premature aging processes in chronic obstructive pulmonary disease and chronic kidney disease. Additionally, organ-specific alterations in proaging mechanisms, which reveal differences in phenotype against a generic background of premature aging, will be addressed. However, within patient populations who share a common diagnosis, clusters of patients with different phenotypes may be identified, which may show overlap with patients with other chronic diseases. SUMMARY: An increased understanding of the premature aging process as well as its systemic consequences may pave the way for 'precision' intervention as well as shared treatment opportunities between chronic debilitating diseases of various causes.

Premature Graying of Hair: An Independent Risk Marker for Coronary Artery Disease in Smokers - A Retrospective Case Control Study.

BACKGROUND: Premature graying of hair as a risk marker among young smokers has a potential of identifying coronary artery disease (CAD) at a very early stage. There is absence of literature that assesses premature graying of hair as an independent marker of CAD in smokers. MATERIAL AND METHODS: The present single-centre case control study enrolled a total of 62 consecutive chronic smokers (≤ 45 years) (Group I) and 60 consecutive young CAD patients (≤45 years) who were chronic smokers (Group II). Another group comprising of 114 patients (≤45 years) having no smoking history and no cardiac ailments either (Group III) was enrolled as control population. All subjects were males. A detailed history and clinical examination regarding conventional coronary risk factors and carotid intima media thickness was done in both groups. RESULTS: The carotid intima media thickness, dyslipidemia and blood pressure were significantly higher in group I and II as compared to group III. When the groups were compared for graying of hair, it was found that the group II (i.e., smokers and CAD) had maximum prevalence of graying which was significantly higher than the control as well as smoker groups. The presence of premature graying of hair was associated with 3.24 times the risk of CAD on multiple logistic regression analysis. CONCLUSION: The presence of premature graying of hair was associated with an increased risk of CAD in young smokers. Premature graying of hair can be used as preliminary evidence by clinicians for classifying patients at risk for premature CAD especially in smokers.