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1.
Molecules ; 26(7)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33805024

RESUMEN

Depression and anxiety disorders are widespread diseases, and they belong to the leading causes of disability and greatest burdens on healthcare systems worldwide. It is expected that the numbers will dramatically rise during the COVID-19 pandemic. Established medications are not sufficient to adequately treat depression and are not available for everyone. Plants from traditional medicine may be promising alternatives to treat depressive symptoms. The model organism Chaenorhabditis elegans was used to assess the stress reducing effects of methanol/dichlormethane extracts from plants used in traditional medicine. After initial screening for antioxidant activity, nine extracts were selected for in vivo testing in oxidative stress, heat stress, and osmotic stress assays. Additionally, anti-aging properties were evaluated in lifespan assay. The extracts from Acanthopanax senticosus, Campsis grandiflora, Centella asiatica, Corydalis yanhusuo, Dan Zhi, Houttuynia cordata, Psoralea corylifolia, Valeriana officinalis, and Withaniasomnifera showed antioxidant activity of more than 15 Trolox equivalents per mg extract. The extracts significantly lowered ROS in mutants, increased resistance to heat stress and osmotic stress, and the extended lifespan of the nematodes. The plant extracts tested showed promising results in increasing stress resistance in the nematode model. Further analyses are needed, in order to unravel underlying mechanisms and transfer results to humans.


Asunto(s)
Antidepresivos/farmacología , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/fisiología , Extractos Vegetales/farmacología , Plantas Medicinales/química , Envejecimiento/efectos de los fármacos , Envejecimiento/fisiología , Animales , Antioxidantes/farmacología , Caenorhabditis elegans/genética , Proteínas de Caenorhabditis elegans/genética , Técnicas de Inactivación de Genes , Respuesta al Choque Térmico/efectos de los fármacos , Longevidad/efectos de los fármacos , Longevidad/genética , Longevidad/fisiología , Mutación , Presión Osmótica/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/química , Especies Reactivas de Oxígeno/metabolismo
2.
Emerg Med Clin North Am ; 39(2): 257-271, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33863458

RESUMEN

Geriatric trauma patients will continue to increase in prevalence as the population ages, and many specific considerations need to be made to provide appropriate care to these patients. This article outlines common presentations of trauma in geriatric patients, with consideration to baseline physiologic function and patterns of injury that may be more prevalent in geriatric populations. Additionally, the article explores specific evidence-based management practices, the significance of trauma team and geriatrician involvement, and disposition decisions.


Asunto(s)
Heridas y Traumatismos/epidemiología , Accidentes por Caídas , Anciano , Envejecimiento/fisiología , Enfermedades Cardiovasculares/fisiopatología , Comorbilidad , Fragilidad/fisiopatología , Geriatras , Accesibilidad a los Servicios de Salud , Humanos , Enfermedades Pulmonares/fisiopatología , Enfermedades Musculoesqueléticas/fisiopatología , Trastornos Neurocognitivos/fisiopatología , Manejo del Dolor , Alta del Paciente , Centros Traumatológicos , Signos Vitales , Heridas y Traumatismos/fisiopatología
3.
Emerg Med Clin North Am ; 39(2): 273-286, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33863459

RESUMEN

In 30 years, adults 65 and older will represent 20% of the US population, with increased medical comorbidities leading to higher rates of critical illness and mortality. Despite significant acute illness, presenting symptoms and vital sign abnormalities may be subtle. Resuscitative guidelines are a helpful starting point but appropriate diagnostics, bedside ultrasound, and frequent reassessments are needed to avoid procrustean care that may worsen outcomes. Baseline functional status is as important as underlying comorbid conditions when prognosticating, and the patient's personal wishes should be sought early and throughout care with clear communication regarding prospects for immediate survival and overall recovery.


Asunto(s)
Enfermedad Crítica/terapia , Resucitación/métodos , Directivas Anticipadas , Anciano , Envejecimiento/fisiología , Enfermedades Cardiovasculares/fisiopatología , Humanos , Enfermedades Renales/fisiopatología , Enfermedades Pulmonares/fisiopatología , Sistemas de Atención de Punto , Insuficiencia Respiratoria/terapia , Choque/diagnóstico , Choque/terapia , Ultrasonografía
4.
Int J Mol Sci ; 22(5)2021 Mar 04.
Artículo en Inglés | MEDLINE | ID: mdl-33806348

RESUMEN

There is substantial genetic variation for common traits associated with reproductive lifespan and for common diseases influencing female fertility. Progress in high-throughput sequencing and genome-wide association studies (GWAS) have transformed our understanding of common genetic risk factors for complex traits and diseases influencing reproductive lifespan and fertility. The data emerging from GWAS demonstrate the utility of genetics to explain epidemiological observations, revealing shared biological pathways linking puberty timing, fertility, reproductive ageing and health outcomes. The observations also identify unique genetic risk factors specific to different reproductive diseases impacting on female fertility. Sequencing in patients with primary ovarian insufficiency (POI) have identified mutations in a large number of genes while GWAS have revealed shared genetic risk factors for POI and ovarian ageing. Studies on age at menopause implicate DNA damage/repair genes with implications for follicle health and ageing. In addition to the discovery of individual genes and pathways, the increasingly powerful studies on common genetic risk factors help interpret the underlying relationships and direction of causation in the regulation of reproductive lifespan, fertility and related traits.


Asunto(s)
Fertilidad/genética , Reproducción/genética , Envejecimiento/genética , Envejecimiento/fisiología , Femenino , Fertilidad/fisiología , Hormona Folículo Estimulante Humana/genética , Hormona Folículo Estimulante Humana/fisiología , Variación Genética , Estudio de Asociación del Genoma Completo , Humanos , Longevidad/genética , Longevidad/fisiología , Hormona Luteinizante/genética , Hormona Luteinizante/fisiología , Menopausia/genética , Menopausia/fisiología , Polimorfismo de Nucleótido Simple , Reproducción/fisiología , Factores de Riesgo
5.
Medicine (Baltimore) ; 100(17): e25361, 2021 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-33907092

RESUMEN

ABSTRACT: We aimed to investigate ovarian reserve status, and explore differences in ovarian reserve between fertile and infertile healthy Chinese women of reproductive age.We recruited 442 fertile women aged 23 to 49 years (mean: 35.22 ±â€Š4.91 years) as subjects, and 196 infertile women aged 23 to 46 years (mean: 32.34 ±â€Š4.34 years) as controls. For all participants, a number of parameters were tested on days 2 to 4 of a spontaneous cycle, including basal serum follicle-stimulating hormone (FSH), estradiol (E2), luteinizing hormone (LH), total testosterone, anti-Müllerian hormone (AMH), ovarian response prediction index (ORPI), and antral follicle count (AFC).There were significant differences in terms of AFC, serum AMH levels, and ORPI among subject subgroups (10.58 ±â€Š5.80; 2.533 ±â€Š2.146 ng/mL; 1.28 ±â€Š1.87; respectively), and among control subgroups (12.44 ±â€Š5.69; 3.189 ±â€Š2.551 ng/mL; 1.88 ±â€Š2.68; respectively) (P < .01 for all). For both subjects and controls, AFC, AMH levels, and ORPI decreased gradually with increasing age, and presented with similar age-related trends; there were positive correlations between AMH and AFC (P < .001), and negative correlations between age and AFC, AMH, ORPI (P < .05 for all). There was a significant difference in age (P < .001), serum E2 (P < .01), and AMH (P < .01) levels between subjects and controls; however, when controlling for confounding factors (age, body mass index, total testosterone, and LH), we found no differences between the 2 groups with regards to the serum levels of AMH, FSH, E2, and AFC (P > .05 for all). Moreover, receiver operating characteristic curve analysis indicated that the significant variables of subjects and controls for evaluating ovarian reserve included age, AMH and ORPI, and ORPI was more valuable than other variables.A diminished ovarian reserve was one of the manifestations caused by female aging. When confounding factors were controlled for, we found no differences in ovarian reserve when compared between fertile and infertile women, and no correlation with infertility.


Asunto(s)
Envejecimiento/fisiología , Fertilidad/fisiología , Infertilidad Femenina/fisiopatología , Reserva Ovárica/fisiología , Adulto , Factores de Edad , Hormona Antimülleriana/sangre , China , Estradiol/sangre , Femenino , Hormona Folículo Estimulante/sangre , Humanos , Infertilidad Femenina/sangre , Hormona Luteinizante/sangre , Persona de Mediana Edad , Folículo Ovárico/crecimiento & desarrollo , Curva ROC , Testosterona/sangre , Adulto Joven
6.
Nutrients ; 13(4)2021 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-33800577

RESUMEN

Nowadays, it is accepted that the regular practice of exercise and branched-chain amino acids supplementation (BCAAs) can benefit the immune responses in older persons, prevent the occurrence of physical frailty (PF), cognitive decline, and aging-related comorbidities. However, the impact of their combination (as non-pharmacological interventions) in albumin and the inflammatory markers is not fully understood. Therefore, we investigated the effect of a 40-week multifactorial intervention [MIP, multicomponent exercise (ME) associated or not with BCAAs] on plasma levels of inflammatory markers and albumin in frail older persons (≥75 years old) living at residential care homes (RCH). This study consisted of a prospective, naturalistic, controlled clinical trial with four arms of multifactorial and experimental (interventions-wahshout-interventions) design. The intervention groups were ME + BCAAs (n = 8), ME (n = 7), BCAAs (n = 7), and control group (n = 13). Lower limb muscle-strength, cognitive profile, and PF tests were concomitantly evaluated with plasma levels of albumin, anti- and pro-inflammatory cytokines [Interleukin-10 (IL-10) and Tumor Necrosis Factor-alpha (TNF-α) respectively], TNF-α/IL-10 ratio, and myeloperoxidase (MPO) activity at four different time-points: Baseline (T1), after 16 weeks of multifactorial intervention (T2), then after a subsequent 8 weeks washout period (T3) and finally, after an additional 16 weeks of multifactorial intervention (T4). Improvement of cognitive profile and muscle strength-related albumin levels, as well as reduction in the TNF-α levels were found particularly in ME plus BCAAs group. No significant variations were observed over time for TNF-α/IL-10 ratio or MPO activity. Overall, the study showed that MIP triggered slight alterations in the inflammatory and physical function of the frail older participants, which could provide independence and higher quality of life for this population.


Asunto(s)
Aminoácidos de Cadena Ramificada/administración & dosificación , Suplementos Dietéticos , Terapia por Ejercicio/métodos , Fragilidad/prevención & control , Albúmina Sérica/metabolismo , Anciano , Anciano de 80 o más Años , Envejecimiento/fisiología , Biomarcadores/sangre , Cognición/fisiología , Disfunción Cognitiva/prevención & control , Citocinas/sangre , Femenino , Anciano Frágil , Evaluación Geriátrica , Humanos , Masculino , Fuerza Muscular/fisiología , Peroxidasa/sangre , Ensayos Clínicos Pragmáticos como Asunto , Estudios Prospectivos , Calidad de Vida
7.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799684

RESUMEN

Age-related hearing loss (ARHL), a sensorineural hearing loss of multifactorial origin, increases its prevalence in aging societies. Besides hearing aids and cochlear implants, there is no FDA approved efficient pharmacotherapy to either cure or prevent ARHL. We hypothesized that selegiline, an antiparkinsonian drug, could be a promising candidate for the treatment due to its complex neuroprotective, antioxidant, antiapoptotic, and dopaminergic neurotransmission enhancing effects. We monitored by repeated Auditory Brainstem Response (ABR) measurements the effect of chronic per os selegiline administration on the hearing function in BALB/c and DBA/2J mice, which strains exhibit moderate and rapid progressive high frequency hearing loss, respectively. The treatments were started at 1 month of age and lasted until almost a year and 5 months of age, respectively. In BALB/c mice, 4 mg/kg selegiline significantly mitigated the progression of ARHL at higher frequencies. Used in a wide dose range (0.15-45 mg/kg), selegiline had no effect in DBA/2J mice. Our results suggest that selegiline can partially preserve the hearing in certain forms of ARHL by alleviating its development. It might also be otoprotective in other mammals or humans.


Asunto(s)
Envejecimiento/fisiología , Modelos Animales de Enfermedad , Pérdida Auditiva Sensorineural/tratamiento farmacológico , Selegilina/farmacología , Administración Oral , Animales , Antiparkinsonianos/administración & dosificación , Antiparkinsonianos/farmacología , Umbral Auditivo/efectos de los fármacos , Umbral Auditivo/fisiología , Potenciales Evocados Auditivos del Tronco Encefálico/efectos de los fármacos , Potenciales Evocados Auditivos del Tronco Encefálico/fisiología , Pérdida Auditiva Sensorineural/fisiopatología , Humanos , Masculino , Ratones Endogámicos BALB C , Ratones Endogámicos DBA , Sustancias Protectoras/administración & dosificación , Sustancias Protectoras/farmacología , Selegilina/administración & dosificación , Transmisión Sináptica/efectos de los fármacos , Transmisión Sináptica/fisiología
8.
Int J Mol Sci ; 22(6)2021 Mar 11.
Artículo en Inglés | MEDLINE | ID: mdl-33799794

RESUMEN

The role of the blood-brain barrier (BBB) breakdown has been recognized as being important in Alzheimer's disease pathogenesis. We aimed to evaluate whether regional BBB integrity differed according to sex and whether differences in BBB integrity changed as a consequence of aging or cognitive decline, using dynamic contrast-enhanced (DCE)-magnetic resonance imaging (MRI). In total, 75 participants with normal cognition (NC) or mild cognitive impairment (MCI) underwent cognitive assessments and MRI examination including DCE-MRI. Regional Ktrans was calculated in cortical regions and the Patlak permeability model was used to calculate BBB permeability (Ktrans, min-1). Females had a lower median Ktrans in the cingulate and occipital cortices. In the "older old" group, sex differences in Ktrans were only observed in the occipital cortex. In the MCI group, sex differences in Ktrans were only observed in the occipital cortex. Age was the only predictor of cognitive assessment scores in the male MCI group; however, educational years and Ktrans in the occipital cortex could predict cognitive scores in the female MCI group. Our study revealed that females may have better BBB integrity in cingulate and occipital cortices. We also found that sex-related differences in BBB integrity are attenuated with aging or cognitive decline.


Asunto(s)
Barrera Hematoencefálica/metabolismo , Encéfalo/metabolismo , Cognición/fisiología , Disfunción Cognitiva/metabolismo , Anciano , Envejecimiento/metabolismo , Envejecimiento/fisiología , Barrera Hematoencefálica/diagnóstico por imagen , Encéfalo/diagnóstico por imagen , Encéfalo/fisiopatología , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Imagen por Resonancia Magnética/métodos , Masculino , Persona de Mediana Edad , Permeabilidad , Factores Sexuales
9.
Dis Model Mech ; 14(1)2021 01 22.
Artículo en Inglés | MEDLINE | ID: mdl-33735102

RESUMEN

Human lifespan is now longer than ever and, as a result, modern society is getting older. Despite that, the detailed mechanisms behind the ageing process and its impact on various tissues and organs remain obscure. In general, changes in DNA, RNA and protein structure throughout life impair their function. Haematopoietic ageing refers to the age-related changes affecting a haematopoietic system. Aged blood cells display different functional aberrations depending on their cell type, which might lead to the development of haematologic disorders, including leukaemias, anaemia or declining immunity. In contrast to traditional bulk assays, which are not suitable to dissect cell-to-cell variation, single-cell-level analysis provides unprecedented insight into the dynamics of age-associated changes in blood. In this Review, we summarise recent studies that dissect haematopoietic ageing at the single-cell level. We discuss what cellular changes occur during haematopoietic ageing at the genomic, transcriptomic, epigenomic and metabolomic level, and provide an overview of the benefits of investigating those changes with single-cell precision. We conclude by considering the potential clinical applications of single-cell techniques in geriatric haematology, focusing on the impact on haematopoietic stem cell transplantation in the elderly and infection studies, including recent COVID-19 research.


Asunto(s)
Envejecimiento/fisiología , Sistema Hematopoyético/fisiología , Análisis de la Célula Individual/métodos , Envejecimiento/genética , Animales , Médula Ósea/fisiología , Daño del ADN , Epigenoma , Glucólisis , Trasplante de Células Madre Hematopoyéticas , Humanos , Mutación , Transcriptoma
10.
Eur J Endocrinol ; 184(5): 667-676, 2021 May.
Artículo en Inglés | MEDLINE | ID: mdl-33667193

RESUMEN

Objective: The objectives of our study were to analyze the influence of age on the survival of patients with RAIR-DTC and to determine their prognostic factors according to age. Methods: This single-center, retrospective study enrolled 155 patients diagnosed with RAIR-DTC. The primary end point was overall survival (OS) according to different cutoff (45, 55, 65, 75 years). Secondary endpoints were progression free survival (PFS) and prognostic factors in patients under and over 65 years. Results: Median OS after RAIR diagnosis was 8.2 years (95% IC: 5.3-9.6). There was no difference according to age with a 65 (P = 0.47) and 55 years old cutoff (P = 0.28). Median OS improved significantly before 45 years old (P = 0.0043). After 75 years old, median OS significantly decreased (P = 0.0008). Median PFS was 2.1 years (95% CI: 0.8-3) in patients < 65 years old, and 1 year in patients ≥ 65 years old (95% CI: 0.8-1.55) with no statistical difference (P = 0.22). There was no impact of age on PFS with any cutoff. In both groups, progressive disease despite 131I treatment reduced OS. In patients < 65 years old, an interval of less than 3 years between the initial diagnosis and the diagnosis of RAIR metastatic disease was predictive of poor survival. In patients > 65 years old, the presence of a mediastinum metastasis was a significant factor for mortality (HR: 4.55, 95% CI: 2.27-9.09). Conclusion: In RAIR-DTC patients, a cut-off age of 65 years old was not a significant predictive factor of survival. Forty-five and 75-years-old cutoff were predictive for OS but not PFS.


Asunto(s)
Adenocarcinoma/mortalidad , Adenocarcinoma/radioterapia , Envejecimiento/fisiología , Radioisótopos de Yodo/uso terapéutico , Neoplasias de la Tiroides/mortalidad , Neoplasias de la Tiroides/radioterapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Factores de Edad , Anciano , Progresión de la Enfermedad , Femenino , Francia/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Análisis de Supervivencia , Neoplasias de la Tiroides/diagnóstico , Neoplasias de la Tiroides/patología , Insuficiencia del Tratamiento , Resultado del Tratamiento
11.
DNA Cell Biol ; 40(4): 629-637, 2021 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-33646053

RESUMEN

Our study aimed at validating the effect of WISP1 on osteoarthritis (OA) and the pathway involved in the WISP1-induced protection against OA. The expression of WISP1 was measured by immunohistochemical analyses. We found that WISP1 expression was shown to be upregulated within human OA cartilage compared with controls. WISP1 expression was related to knee OA severity. rhWISP1 inhibited OA chondrocyte senescence and apoptosis in vitro, which was reversed by the αvß3 antibody and PI3K/Akt inhibitor LY294002. WISP1 overexpression induced by knee injection of LiCI could also prevent the senescence and apoptosis of rat chondrocytes. Safranin-O staining and Mankin score revealed that WISP1 overexpression can protect rat chondrocytes from degeneration. Nearly opposite results were obtained in the treatment of ICG-001 and siRNA-WISP1 in vivo. These data strongly suggest that WISP1 can protect against the senescence and apoptosis of chondrocytes via modulating the αvß3 receptor and PI3K/Akt signaling pathway within OA. Therefore, the development of specific activators of WISP1 may present the value of an underlying OA treatment.


Asunto(s)
Proteínas CCN de Señalización Intercelular/metabolismo , Condrocitos/metabolismo , Osteoartritis de la Rodilla/metabolismo , Proteínas Proto-Oncogénicas/metabolismo , Adulto , Envejecimiento/fisiología , Animales , Apoptosis/fisiología , Proteínas CCN de Señalización Intercelular/fisiología , Cartílago Articular/metabolismo , Femenino , Humanos , Integrina alfaVbeta3/metabolismo , Interleucina-1beta/metabolismo , Masculino , MicroARNs/metabolismo , Persona de Mediana Edad , Osteoartritis/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas/fisiología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Ratas , Ratas Sprague-Dawley , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo
12.
Nat Commun ; 12(1): 1826, 2021 03 23.
Artículo en Inglés | MEDLINE | ID: mdl-33758188

RESUMEN

Somatic mutations of ASXL1 are frequently detected in age-related clonal hematopoiesis (CH). However, how ASXL1 mutations drive CH remains elusive. Using knockin (KI) mice expressing a C-terminally truncated form of ASXL1-mutant (ASXL1-MT), we examined the influence of ASXL1-MT on physiological aging in hematopoietic stem cells (HSCs). HSCs expressing ASXL1-MT display competitive disadvantage after transplantation. Nevertheless, in genetic mosaic mouse model, they acquire clonal advantage during aging, recapitulating CH in humans. Mechanistically, ASXL1-MT cooperates with BAP1 to deubiquitinate and activate AKT. Overactive Akt/mTOR signaling induced by ASXL1-MT results in aberrant proliferation and dysfunction of HSCs associated with age-related accumulation of DNA damage. Treatment with an mTOR inhibitor rapamycin ameliorates aberrant expansion of the HSC compartment as well as dysregulated hematopoiesis in aged ASXL1-MT KI mice. Our findings suggest that ASXL1-MT provokes dysfunction of HSCs, whereas it confers clonal advantage on HSCs over time, leading to the development of CH.


Asunto(s)
Envejecimiento/genética , Hematopoyesis/genética , Células Madre Hematopoyéticas/metabolismo , Proteínas Represoras/genética , Serina-Treonina Quinasas TOR/metabolismo , Anciano , Envejecimiento/metabolismo , Envejecimiento/fisiología , Animales , Apoptosis/genética , Ciclo Celular/genética , Proliferación Celular/genética , Células Cultivadas , Daño del ADN/efectos de los fármacos , Daño del ADN/genética , Técnicas de Sustitución del Gen , Hematopoyesis/fisiología , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/efectos de los fármacos , Células Madre Hematopoyéticas/fisiología , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Potencial de la Membrana Mitocondrial/genética , Ratones , Ratones Transgénicos , Mutación , Proteínas Proto-Oncogénicas c-akt/metabolismo , RNA-Seq , Especies Reactivas de Oxígeno/farmacología , Proteínas Represoras/metabolismo , Transducción de Señal/efectos de los fármacos , Transducción de Señal/genética , Sirolimus/farmacología , Proteínas Supresoras de Tumor/metabolismo , Ubiquitina Tiolesterasa/metabolismo , Ubiquitinación/efectos de los fármacos , Ubiquitinación/genética
13.
Int J Mol Sci ; 22(4)2021 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-33669795

RESUMEN

AdipoRon, an adiponectin receptor agonist, elicits similar antidiabetic, anti-atherogenic, and anti-inflammatory effects on mouse models as adiponectin does. Since AdipoRon can cross the blood-brain barrier, its chronic effects on regulating hippocampal function are yet to be examined. This study investigated whether AdipoRon treatment promotes hippocampal neurogenesis and spatial recognition memory in a dose-dependent manner. Adolescent male C57BL/6J mice received continuous treatment of either 20 mg/kg (low dose) or 50 mg/kg (high dose) AdipoRon or vehicle intraperitoneally for 14 days, followed by the open field test to examine anxiety and locomotor activity, and the Y maze test to examine hippocampal-dependent spatial recognition memory. Immunopositive cell markers of neural progenitor cells, immature neurons, and newborn cells in the hippocampal dentate gyrus were quantified. Immunosorbent assays were used to measure the serum levels of factors that can regulate hippocampal neurogenesis, including adiponectin, brain-derived neurotrophic factor (BDNF), and corticosterone. Our results showed that 20 mg/kg AdipoRon treatment significantly promoted hippocampal cell proliferation and increased serum levels of adiponectin and BDNF, though there were no effects on spatial recognition memory and locomotor activity. On the contrary, 50 mg/kg AdipoRon treatment impaired spatial recognition memory, suppressed cell proliferation, neuronal differentiation, and cell survival associated with reduced serum levels of BDNF and adiponectin. The results suggest that a low-dose AdipoRon treatment promotes hippocampal cell proliferation, while a high-dose AdipoRon treatment is detrimental to the hippocampus function.


Asunto(s)
Envejecimiento/fisiología , Hipocampo/fisiología , Neurogénesis/efectos de los fármacos , Piperidinas/farmacología , Adiponectina/sangre , Animales , Glucemia/metabolismo , Factor Neurotrófico Derivado del Encéfalo/sangre , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Corticosterona/sangre , Giro Dentado/efectos de los fármacos , Giro Dentado/fisiología , Hipocampo/efectos de los fármacos , Masculino , Ratones Endogámicos C57BL , Modelos Biológicos , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Neuronas/metabolismo , Memoria Espacial/efectos de los fármacos
14.
Nat Commun ; 12(1): 1418, 2021 03 03.
Artículo en Inglés | MEDLINE | ID: mdl-33658508

RESUMEN

Sarcopenia is a degenerative condition that consists in age-induced atrophy and functional decline of skeletal muscle cells (myofibers). A common hypothesis is that inducing myofiber hypertrophy should also reinstate myofiber contractile function but such model has not been extensively tested. Here, we find that the levels of the ubiquitin ligase UBR4 increase in skeletal muscle with aging, and that UBR4 increases the proteolytic activity of the proteasome. Importantly, muscle-specific UBR4 loss rescues age-associated myofiber atrophy in mice. However, UBR4 loss reduces the muscle specific force and accelerates the decline in muscle protein quality that occurs with aging in mice. Similarly, hypertrophic signaling induced via muscle-specific loss of UBR4/poe and of ESCRT members (HGS/Hrs, STAM, USP8) that degrade ubiquitinated membrane proteins compromises muscle function and shortens lifespan in Drosophila by reducing protein quality control. Altogether, these findings indicate that these ubiquitin ligases antithetically regulate myofiber size and muscle protein quality control.


Asunto(s)
Envejecimiento/fisiología , Proteínas de Unión a Calmodulina/metabolismo , Proteínas de Drosophila/metabolismo , Fibras Musculares Esqueléticas/fisiología , Proteínas Musculares/metabolismo , Ubiquitina-Proteína Ligasas/metabolismo , Animales , Animales Modificados Genéticamente , Autofagia/fisiología , Proteínas de Unión a Calmodulina/genética , Proteínas de Drosophila/genética , Femenino , Lisosomas/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Fibras Musculares Esqueléticas/metabolismo , Músculo Esquelético/patología , Músculo Esquelético/fisiología , Proteolisis , Ubiquitina/metabolismo , Ubiquitina-Proteína Ligasas/genética
15.
Public Health ; 192: 61-67, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33640798

RESUMEN

OBJECTIVES: Ageing is related to physical, psychological and social conditions. The aim of this study was to develop a scale that comprehensively assesses these three dimensions to reflect the ageing state of the human body. STUDY DESIGN: The study design of this study is a cross-sectional study. METHODS: The items for the preliminary scale were selected from relevant high-quality literature. The preliminary scale was developed by experts through two rounds of the Delphi method. The analytic hierarchy process was used to determine the weights of the items. Cronbach's α, the test-retest reliability, the content validity index and exploratory factor analysis (EFA) were used to evaluate the validity and reliability of the scale. RESULTS: This study developed the Physiological-Psychological-Social Three-dimensional Human Ageing Scale (PPSHAS), which includes 3 dimensions, 10 components and 51 items. The Cronbach's α of the PPSHAS was 0.930, and the test-retest reliability coefficient was 0.856 (P < 0.001). The scale-level content validity index/universal agreement was 0.82, and the scale-level content validity index/average was 0.98. The EFA yielded 10 components; the total variance explained by these components was 57.491%. CONCLUSIONS: This PPSHAS is an easy-to-use instrument for assessing the ageing process among elderly people and has adequate validity and reliability.


Asunto(s)
Envejecimiento/fisiología , Envejecimiento/psicología , Adulto , Anciano , Anciano de 80 o más Años , Estudios Transversales , Análisis Factorial , Femenino , Evaluación Geriátrica , Humanos , Masculino , Persona de Mediana Edad , Psicometría , Reproducibilidad de los Resultados , Encuestas y Cuestionarios
16.
Methods Mol Biol ; 2224: 61-74, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33606206

RESUMEN

The mammalian hippocampus shows a remarkable capacity for continued neurogenesis throughout life. Newborn neurons, generated by the radial neural stem cells (NSCs), are important for learning and memory as well as mood control. During aging, the number and responses of NSCs to neurogenic stimuli diminish, leading to decreased neurogenesis and age-associated cognitive decline and psychiatric disorders. Thus, adult hippocampal neurogenesis has been the subject of intense investigation, generating both excitement and controversy. Identifying the core molecular machinery responsible for NSC preservation is of fundamental importance if we are to use neurogenesis to halt or reverse hippocampal age-related pathology. Here, we briefly overview the most frequently used mouse models to study hippocampal neurogenesis and then focus on a unique mouse model that allows NSC-specific studies based on their unique expression of lunatic fringe (Lfng). The Lfng-eGFP and Lfng(BAC)-CreERT2;RCL-tdT transgenic mice provide us with an excellent tool to resolve long-standing questions regarding the properties of NSCs, such as their specific molecular composition, potency, and plasticity, in isolation from any other cell in the hippocampal neurogenic niche.


Asunto(s)
Hipocampo/fisiología , Células-Madre Neurales/fisiología , Células Madre Adultas/fisiología , Envejecimiento/fisiología , Animales , Biología , Disfunción Cognitiva/fisiopatología , Ratones , Ratones Transgénicos , Modelos Animales , Neurogénesis/fisiología , Neuronas/fisiología
17.
Nat Commun ; 12(1): 1024, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33589624

RESUMEN

Given the severity of the SARS-CoV-2 pandemic, a major challenge is to rapidly repurpose existing approved drugs for clinical interventions. While a number of data-driven and experimental approaches have been suggested in the context of drug repurposing, a platform that systematically integrates available transcriptomic, proteomic and structural data is missing. More importantly, given that SARS-CoV-2 pathogenicity is highly age-dependent, it is critical to integrate aging signatures into drug discovery platforms. We here take advantage of large-scale transcriptional drug screens combined with RNA-seq data of the lung epithelium with SARS-CoV-2 infection as well as the aging lung. To identify robust druggable protein targets, we propose a principled causal framework that makes use of multiple data modalities. Our analysis highlights the importance of serine/threonine and tyrosine kinases as potential targets that intersect the SARS-CoV-2 and aging pathways. By integrating transcriptomic, proteomic and structural data that is available for many diseases, our drug discovery platform is broadly applicable. Rigorous in vitro experiments as well as clinical trials are needed to validate the identified candidate drugs.


Asunto(s)
Envejecimiento/fisiología , /genética , Reposicionamiento de Medicamentos , Células A549 , Algoritmos , Antivirales/uso terapéutico , Descubrimiento de Drogas , Expresión Génica , Redes Reguladoras de Genes , Humanos , Proteómica , Transcriptoma
18.
Maturitas ; 145: 78-85, 2021 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-33541567

RESUMEN

BACKGROUND: Androgen deficiency of aging males (ADAM) largely manifests as sexual symptoms. Erectile dysfunction is one of the most common symptoms of ADAM. AIM: To ascertain the effect of concurrent training and supplementation with Eurycoma longifolia on erectile function and testosterone levels in men with ADAM, and the association of erectile function with levels of total testosterone. METHODS: 6-month, randomized, double-blind, placebo-controlled four-arm clinical. 45 men (47.38 ± 5.03 years) were randomized into 4 groups (G1: control + placebo; G2: control + Eurycoma longifolia; G3: concurrent training + placebo; G4: concurrent training + Eurycoma longifolia). 22 received a 200 mg supplement of Eurycoma longifolia and 23 underwent the intervention with concurrent training, 3 times a week for 60 min at progressive intensity. OUTCOMES: International Index of Erectile Function (IIEF-5), Aging Male Scale (AMS) and total testosterone. RESULTS: Erectile function demonstrated improvements in both interventions; however, the most significant results were obtained by men allocated to concurrent training + Eurycoma longifolia. CLINICAL IMPLICATIONS: A 200 mg supplement of Eurycoma longifolia and the practice of concurrent training for 6 months significantly improved the erectile function of men with ADAM. STRENGTHS & LIMITATIONS: The study's design stands out as a strength, in addition to the six-month intervention. The main limitation is the study not having groups that used only Eurycoma longifolia and only concurrent training. CONCLUSION: The combination of Eurycoma longifolia and concurrent training improved erectile function and increased total testosterone levels in men with ADAM.


Asunto(s)
Disfunción Eréctil/terapia , Eurycoma , Ejercicio Físico , Extractos Vegetales/uso terapéutico , Adulto , Envejecimiento/sangre , Envejecimiento/fisiología , Andrógenos/sangre , Andrógenos/deficiencia , Método Doble Ciego , Disfunción Eréctil/sangre , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Testosterona/sangre , Testosterona/deficiencia
19.
Horm Mol Biol Clin Investig ; 42(1): 87-98, 2021 Feb 04.
Artículo en Inglés | MEDLINE | ID: mdl-33544506

RESUMEN

The COVID-19 pandemic has not only led to a worldwide socio-economic depression, but has also had the highest health impact on the geriatric population. Elderly population, due to various reasons such as low immunity, pre-existing co-morbidities such as hypertension, cardiovascular diseases or diabetes, are obviously predisposed to develop severe infections and exhibit a high mortality rate. This is because of many reasons which include the atypical presentation in the geriatric population which might have led to diagnostic delay. As per the WHO guidelines to perform RT-PCR only on the symptomatic individuals, a very small portion of individuals were tested, leaving a fraction of population undiagnosed. Therefore, there remained a chance that many asymptomatic individuals such caregivers, healthcare professionals, family members were undiagnosed and might have carried this virus to the geriatric patients. Also, many countries were not prepared to handle the burden on their healthcare system which included sudden increased demand of ICU beds, mechanical ventilation etc. As a result, they had to make decision on who to be admitted. Atypical presentation in geriatric population may include afebrile or low-grade fever, absence of cough, malaise, muscle pains, dyspnoea etc. Geriatric population shows a more severe type of pneumonia, significantly higher number of neutrophils and C-reactive protein, less lymphocytes and a higher proportion of multiple lobe involvement. Extreme social suppression during COVID-19 pandemic has increased the risk of mental and physical adverse effects that has made older adults more vulnerable to depression and anxiety.


Asunto(s)
Envejecimiento/fisiología , /patología , Factores de Edad , Anciano , Anciano de 80 o más Años , Envejecimiento/inmunología , /inmunología , Diagnóstico Tardío , Geriatría , Humanos , Persona de Mediana Edad , Pandemias , Pronóstico , Índice de Severidad de la Enfermedad
20.
Neuron ; 109(7): 1100-1117.e10, 2021 04 07.
Artículo en Inglés | MEDLINE | ID: mdl-33606969

RESUMEN

Aging results in gray and white matter degeneration, but the specific microglial responses are unknown. Using single-cell RNA sequencing from white and gray matter separately, we identified white matter-associated microglia (WAMs), which share parts of the disease-associated microglia (DAM) gene signature and are characterized by activation of genes implicated in phagocytic activity and lipid metabolism. WAMs depend on triggering receptor expressed on myeloid cells 2 (TREM2) signaling and are aging dependent. In the aged brain, WAMs form independent of apolipoprotein E (APOE), in contrast to mouse models of Alzheimer's disease, in which microglia with the WAM gene signature are generated prematurely and in an APOE-dependent pathway similar to DAMs. Within the white matter, microglia frequently cluster in nodules, where they are engaged in clearing degenerated myelin. Thus, WAMs may represent a potentially protective response required to clear degenerated myelin accumulating during white matter aging and disease.


Asunto(s)
Microglía/fisiología , Sustancia Blanca/citología , Sustancia Blanca/crecimiento & desarrollo , Envejecimiento/fisiología , Enfermedad de Alzheimer/genética , Animales , Apolipoproteínas E/genética , Enfermedades Desmielinizantes/patología , Regulación de la Expresión Génica , Sustancia Gris/citología , Sustancia Gris/crecimiento & desarrollo , Inmunohistoquímica , Glicoproteínas de Membrana/biosíntesis , Glicoproteínas de Membrana/genética , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Microglía/ultraestructura , Vaina de Mielina/metabolismo , Receptores Inmunológicos/biosíntesis , Receptores Inmunológicos/genética , Análisis de Secuencia de ARN , Transducción de Señal/fisiología , Análisis de la Célula Individual
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