RESUMEN
The Dog Aging Project is a long-term longitudinal study of ageing in tens of thousands of companion dogs. The domestic dog is among the most variable mammal species in terms of morphology, behaviour, risk of age-related disease and life expectancy. Given that dogs share the human environment and have a sophisticated healthcare system but are much shorter-lived than people, they offer a unique opportunity to identify the genetic, environmental and lifestyle factors associated with healthy lifespan. To take advantage of this opportunity, the Dog Aging Project will collect extensive survey data, environmental information, electronic veterinary medical records, genome-wide sequence information, clinicopathology and molecular phenotypes derived from blood cells, plasma and faecal samples. Here, we describe the specific goals and design of the Dog Aging Project and discuss the potential for this open-data, community science study to greatly enhance understanding of ageing in a genetically variable, socially relevant species living in a complex environment.
Asunto(s)
Envejecimiento/fisiología , Perros/fisiología , Difusión de la Información , Mascotas/fisiología , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Animales , Biomarcadores , Entorno Construido , Ensayos Clínicos Veterinarios como Asunto , Estudios Transversales , Recolección de Datos , Perros/genética , Femenino , Fragilidad/veterinaria , Interacción Gen-Ambiente , Estudio de Asociación del Genoma Completo , Objetivos , Envejecimiento Saludable/efectos de los fármacos , Humanos , Inflamación/veterinaria , Consentimiento Informado , Estilo de Vida , Longevidad/efectos de los fármacos , Longevidad/genética , Longevidad/fisiología , Estudios Longitudinales , Masculino , Modelos Animales , Multimorbilidad , Mascotas/genética , Privacidad , Sirolimus/farmacologíaRESUMEN
For several decades, understanding ageing and the processes that limit lifespan have challenged biologists. Thirty years ago, the biology of ageing gained unprecedented scientific credibility through the identification of gene variants that extend the lifespan of multicellular model organisms. Here we summarize the milestones that mark this scientific triumph, discuss different ageing pathways and processes, and suggest that ageing research is entering a new era that has unique medical, commercial and societal implications. We argue that this era marks an inflection point, not only in ageing research but also for all biological research that affects the human healthspan.
Asunto(s)
Envejecimiento/fisiología , Investigación Biomédica , Envejecimiento Saludable/fisiología , Rejuvenecimiento/fisiología , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Relojes Circadianos , Ensayos Clínicos como Asunto , Envejecimiento Saludable/efectos de los fármacos , Envejecimiento Saludable/genética , Humanos , Inflamación , Longevidad/efectos de los fármacos , Longevidad/genética , Longevidad/fisiología , Mitocondrias/metabolismo , Estado Nutricional , Estrés Oxidativo , Transducción de SeñalRESUMEN
Frailty is a geriatric syndrome associated with both locomotor and cognitive decline, typically linked to chronic systemic inflammation, i.e., inflammaging. In the current study, we investigated the effect of a two-month oral supplementation with standardized extracts of H. erinaceus, containing a known amount of Erinacine A, Hericenone C, Hericenone D, and L-ergothioneine, on locomotor frailty and cerebellum of aged mice. Locomotor performances were monitored comparing healthy aging and frail mice. Cerebellar volume and cytoarchitecture, together with inflammatory and oxidative stress pathways, were assessed focusing on senescent frail animals. H. erinaceus partially recovered the aged-related decline of locomotor performances. Histopathological analyses paralleled by immunocytochemical evaluation of specific molecules strengthened the neuroprotective role of H. erinaceus able to ameliorate cerebellar alterations, i.e., milder volume reduction, slighter molecular layer thickness decrease and minor percentage of shrunken Purkinje neurons, also diminishing inflammation and oxidative stress in frail mice while increasing a key longevity regulator and a neuroprotective molecule. Thus, our present findings demonstrated the efficacy of a non-pharmacological approach, based on the dietary supplementation using H. erinaceus extract, which represent a promising adjuvant therapy to be associated with conventional geriatric treatments.
Asunto(s)
Envejecimiento Saludable/fisiología , Hericium/metabolismo , Neuroprotección , Animales , Ciclooxigenasa 2/metabolismo , Fragilidad/metabolismo , Fragilidad/fisiopatología , Proteína Ácida Fibrilar de la Glía/metabolismo , Envejecimiento Saludable/efectos de los fármacos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Inflamación/patología , Interleucina-6/metabolismo , Masculino , Ratones Endogámicos C57BL , Actividad Motora/efectos de los fármacos , Neuroprotección/efectos de los fármacos , Óxido Nítrico Sintasa de Tipo II/metabolismo , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Sirtuina 1/metabolismo , Superóxido Dismutasa/metabolismoRESUMEN
Pharmaceutical interventions can slow aging in animals, and have advantages because their dose can be tightly regulated and the timing of the intervention can be closely controlled. They also may complement environmental interventions like caloric restriction by acting additively. A fertile source for therapies slowing aging is FDA approved drugs whose safety has been investigated. Because drugs bind to several protein targets, they cause multiple effects, many of which have not been characterized. It is possible that some of the side effects of drugs prescribed for one therapy may have benefits in retarding aging. We used computationally guided drug screening for prioritizing drug targets to produce a short list of candidate compounds for in vivo testing. We applied the virtual ligand screening approach FINDSITEcomb for screening potential anti-aging protein targets against FDA approved drugs listed in DrugBank. A short list of 31 promising compounds was screened using a multi-tiered approach with rotifers as an animal model of aging. Primary and secondary survival screens and cohort life table experiments identified four drugs capable of extending rotifer lifespan by 8-42%. Exposures to 1 µM erythromycin, 5 µM carglumic acid, 3 µM capecitabine, and 1 µM ivermectin, extended rotifer lifespan without significant effect on reproduction. Some drugs also extended healthspan, as estimated by mitochondria activity and mobility (swimming speed). Our most promising result is that rotifer lifespan was extended by 7-8.9% even when treatment was started in middle age.
Asunto(s)
Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Rotíferos/efectos de los fármacos , Rotíferos/genética , Envejecimiento/fisiología , Animales , Capecitabina/farmacología , Bases de Datos Farmacéuticas , Evaluación Preclínica de Medicamentos/métodos , Evaluación Preclínica de Medicamentos/estadística & datos numéricos , Reposicionamiento de Medicamentos , Eritromicina/farmacología , Femenino , Genes de Helminto/efectos de los fármacos , Glutamatos/farmacología , Envejecimiento Saludable/efectos de los fármacos , Envejecimiento Saludable/genética , Envejecimiento Saludable/fisiología , Longevidad/efectos de los fármacos , Longevidad/genética , Longevidad/fisiología , Masculino , Modelos Animales , Pravastatina/farmacología , Reproducción/efectos de los fármacos , Rotíferos/fisiología , Estados Unidos , United States Food and Drug Administration , Interfaz Usuario-ComputadorRESUMEN
There is a rapid increase in the percentage of elderly people in Europe. Consequently, the prevalence of age-related diseases will also significantly increase. Therefore, the main goal of MediHealth, an international research project, is to introduce a novel approach for the discovery of active agents of food plants from the Mediterranean diet and other global sources that promote healthy ageing. To achieve this goal, a series of plants from the Mediterranean diet and food plants from other origins are carefully selected and subjected to in silico, cell-based, in vivo (fly and mouse models), and metabolism analyses. Advanced analytical techniques complement the bio-evaluation process for the efficient isolation and identification of the bioactive plant constituents. Furthermore, pharmacological profiling of bioactive natural products, as well as the identification and synthesis of their metabolites, is carried out. Finally, optimization studies are performed in order to proceed to the development of innovative nutraceuticals, dietary supplements or herbal medicinal products. The project is based on an exchange of researchers between nine universities and four companies from European and non-European countries, exploiting the existing complementary multidisciplinary expertise. Herein, the unique and novel approach of this interdisciplinary project is presented.
Asunto(s)
Productos Biológicos/química , Dieta Mediterránea , Suplementos Dietéticos/análisis , Envejecimiento Saludable/efectos de los fármacos , Fitoquímicos/aislamiento & purificación , Plantas Comestibles/química , Animales , Disponibilidad Biológica , Productos Biológicos/farmacocinética , Productos Biológicos/farmacología , Drosophila melanogaster/efectos de los fármacos , Drosophila melanogaster/fisiología , Envejecimiento Saludable/fisiología , Humanos , Comunicación Interdisciplinaria , Cooperación Internacional , Ratones , Ratones Endogámicos C57BL , Ciencias de la Nutrición/instrumentación , Ciencias de la Nutrición/métodos , Fitoquímicos/química , Plantas Medicinales/químicaRESUMEN
Healthy aging has emerged as a crucial issue with the increase in the geriatric population worldwide. Food-derived sulfur-containing amino acid ergothioneine (ERGO) is a potential dietary supplement, which exhibits various beneficial effects in experimental animals although the preventive effects of ERGO on aging and/or age-related impairments such as frailty and cognitive impairment are unclear. We investigated the effects of daily oral supplementation of ERGO dissolved in drinking water on lifespan, frailty, and cognitive impairment in male mice from 7 weeks of age to the end of their lives. Ingestion of 4 ~ 5 mg/kg/day of ERGO remarkably extended the lifespan of male mice. The longevity effect of ERGO was further supported by increase in life and non-frailty spans of Caenorhabditis elegans in the presence of ERGO. Compared with the control group, the ERGO group showed significantly lower age-related declines in weight, fat mass, and average and maximum movement velocities at 88 weeks of age. This was compatible with dramatical suppression by ERGO of the age-related increments in plasma biomarkers (BMs) such as the chemokine ligand 9, creatinine, symmetric dimethylarginine, urea, asymmetric dimethylarginine, quinolinic acid, and kynurenine. The oral intake of ERGO also rescued age-related impairments in learning and memory ability, which might be associated with suppression of the age-related decline in hippocampal neurogenesis and TDP43 protein aggregation and promotion of microglial shift to the M2 phenotype by ERGO ingestion. Ingestion of ERGO may promote longevity and healthy aging in male mice, possibly through multiple biological mechanisms.
Asunto(s)
Caenorhabditis elegans , Ergotioneína , Envejecimiento Saludable , Longevidad , Animales , Ergotioneína/farmacología , Masculino , Longevidad/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Caenorhabditis elegans/efectos de los fármacos , Ratones , Suplementos Dietéticos , Ratones Endogámicos C57BL , FragilidadRESUMEN
Reversing age-associated taurine loss improves mouse longevity and monkey health.
Asunto(s)
Envejecimiento Saludable , Taurina , Animales , Ratones , Envejecimiento Saludable/efectos de los fármacos , Envejecimiento Saludable/metabolismo , Longevidad , Taurina/sangre , Taurina/deficiencia , Taurina/farmacología , HaplorrinosRESUMEN
Lithium is a nutritional trace element, used clinically as an anti-depressant. Preclinically, lithium has neuroprotective effects in invertebrates and mice, and it can also extend lifespan in fission yeast, C. elegans and Drosophila. An inverse correlation of human mortality with the concentration of lithium in tap water suggests a possible, evolutionarily conserved mechanism mediating longevity. Here, we assessed the effects of lithium treatment on lifespan and ageing parameters in mice. Lithium has a narrow therapeutic dose range, and overdosing can severely affect organ health. Within the tolerable dosing range, we saw some mildly positive effects of lithium on health span but not on lifespan.
Asunto(s)
Envejecimiento/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Litio/uso terapéutico , Animales , Humanos , Litio/farmacología , Masculino , RatonesRESUMEN
Preservation of a robust circadian rhythmicity (particulsarly of the sleep/wake cycle), a proper nutrition and adequate physical exercise are key elements for healthy aging. Aging comes along with circadian alteration, e.g. a disrupted sleep and inflammation, that leads to metabolic disorders. In turn, sleep cycle disturbances cause numerous pathophysiological changes that accelerates the aging process. In the central nervous system, sleep disruption impairs several functions, among them, the clearance of waste molecules. The decrease of plasma melatonin, a molecule of unusual phylogenetic conservation present in all known aerobic organisms, plays a particular role as far as the endocrine sequels of aging. Every day, the late afternoon/nocturnal increase of melatonin synchronizes both the central circadian pacemaker located in the hypothalamic suprachiasmatic nuclei as well as myriads of peripheral cellular circadian clocks. This is called the "chronobiotic effect" of melatonin, the methoxyindole being the prototype of the endogenous family of chronobiotic agents. In addition, melatonin exerts a significant cytoprotective action by buffering free radicals and reversing inflammation via down regulation of proinflammatory cytokines, suppression of low degree inflammation and prevention of insulin resistance. Because of these properties melatonin has been advocated to be a potential therapeutic tool in COVID 19 pandemic. Melatonin administration to aged animals counteracts a significant number of senescence-related changes. In humans, melatonin is effective both as a chronobiotic and a cytoprotective agent to maintain a healthy aging. Circulating melatonin levels are consistently reduced in the metabolic syndrome, ischemic and non-ischemic cardiovascular diseases and neurodegenerative disorders like the Alzheimer's and Parkinson's diseases. The potential therapeutic value of melatonin has been suggested by a limited number of clinical trials generally employing melatonin in the 2-10mg/day range. However, from animal studies the cytoprotective effects of melatonin need higher doses to become apparent (i.e. in the 100mg/day range). Hence, controlled studies employing melatonin doses in this range are urgently needed.
Asunto(s)
Antioxidantes/farmacología , Ritmo Circadiano/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Melatonina/farmacología , Animales , Antioxidantes/uso terapéutico , Humanos , Melatonina/uso terapéuticoRESUMEN
The aim of a 12-week randomized double-blind placebo-controlled study was to assess the effect of daily supplementation with a natural extract of Spinacia oleracea L. (4 × 500 mg capsules/day; total 2 g per day) combined with a moderate-intensity training program (1 h session/3 times a week) on skeletal muscle fitness in adults over 50 years of age. Muscle strength assessed by isokinetic and isometric dynamometry improved significantly in the experimental (n = 23) and the placebo (n = 22) groups, but the magnitude of improvement was higher in the experimental group, with between-group differences in almost all variables, including isokinetic at 60° s-1 in knee extension, peak torque (p < 0.007); total work per repetition maximum (p < 0.009); isokinetic at 180°s-1 in knee extension, peak torque (p < 0.002); total work (p < 0.007); total work per repetition maximum (p < 0.005); average power (p < 0.027); isometric in knee extension, peak torque (p < 0.005); and average peak torque (p < 0.002). Similar findings were observed for muscle quality. Changes in quality of life (SF-36) were not found, except for improvements in the role physical (p < 0.023) and role emotional (p < 0.001) domains, likely as a result of the physical training sessions. A nutritional survey did not revealed changes in dietary habits. No adverse events were recorded. In subjects over 50 years of age, moderate-intensity strength training combined with daily supplementation for 12 weeks with a natural extract of Spinacia oleracea L. improved muscle-related variables and muscle quality. Maintaining muscle health is a key component of healthy aging.
Asunto(s)
Suplementos Dietéticos , Fuerza Muscular/efectos de los fármacos , Músculo Esquelético/fisiología , Extractos Vegetales/administración & dosificación , Extractos Vegetales/farmacología , Sarcopenia/prevención & control , Spinacia oleracea/química , Factores de Edad , Anciano , Método Doble Ciego , Femenino , Envejecimiento Saludable/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Fitoterapia , Sarcopenia/fisiopatología , Factores de TiempoRESUMEN
Healthy aging and human longevity are intricate phenotypes affected by environmental factors such as physical exercise, diet, health habits, and psychosocial situations as well as genetic factors. Diet and caloric restriction have a crucial role in healthy aging. Curcumin, a polyphenolic compound isolated from the Curcuma longa, has been shown to exert anti-aging characteristics. Recently, investigations on curcumin with regard to aging and age-associated disease in model organisms has described that curcumin and its metabolites, prolong the mean lifespan of some aging model organisms such as C. elegans, D. melanogaster, yeast, and mouse. It has been proposed to have several biological activities, such as antioxidative, anti-inflammatory, anticancer, chemopreventive, and anti-neurodegenerative characteristics. In several studies on various model organisms it has been shown that the lifespan extension via curcumin treatment was connected with enhanced superoxide dismutase (SOD) activity, and also declined malondialdehyde (MDA) and lipofuscin levels. As well as the pivotal role of curcumin on the modulating of major signaling pathways that influence longevity of organisms like IIS, mTOR, PKA, and FOXO signaling pathways. This review defines the use of curcumin in traditional and modern medicine, its biochemistry and biological functions, such as curcumin's anti-aging, anti-cancer, anti-microbial, anti-inflammatory, and anti-oxidant characteristics. Also, the review further describes the role of curcumin in a pharmacological context and new insights on its therapeutic capacity and restrictions. Particularly, the review emphasizes in-depth on the efficiency of curcumin and its mechanism of action as an anti-aging compound and also treating age-related disease.
Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Senescencia Celular/efectos de los fármacos , Curcumina/uso terapéutico , Envejecimiento Saludable/efectos de los fármacos , Factores de Edad , Animales , Antiinflamatorios/efectos adversos , Antioxidantes/efectos adversos , Curcumina/efectos adversos , Humanos , Mediadores de Inflamación/metabolismo , Estrés Oxidativo/efectos de los fármacos , Transducción de SeñalRESUMEN
Drosophila are widely used to study neural development, immunity, and inflammatory pathways and processes associated with the gut-brain axis. Here, we examine the response of adult Drosophila given an inactive bacteriologic (IAB; proprietary lysate preparation of Lactobacillus bulgaricus, ReseT®) and a probiotic (Lactobacillus rhamnosus, LGG). In vitro, the IAB activates a subset of conserved Toll-like receptor (TLR) and nucleotide-binding, oligomerization domain-containing protein (NOD) receptors in human cells, and oral administration slowed the age-related decline of adult Drosophila locomotor behaviors. On average, IAB-treated flies lived significantly longer (+23%) and had lower neural aggregate profiles. Different IAB dosages also improved locomotor function and longevity profiles after traumatic brain injury (TBI) exposure. Mechanistically, short-term IAB and LGG treatment altered baseline nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κß) signaling profiles in neural and abdominal tissues. Overall, at select dosages, IAB and LGG exposure has a positive impact on Drosophila longevity, neural aging, and mild traumatic brain injury (TBI)-related responses, with IAB showing greater benefit. This includes severe TBI (sTBI) responses, where IAB treatment was protective and LGG increased acute mortality profiles. This work shows that Drosophila are an effective model for testing bacterial-based biologics, that IAB and probiotic treatments promote neuronal health and influence inflammatory pathways in neural and immune tissues. Therefore, targeted IAB treatments are a novel strategy to promote the appropriate function of the gut-brain axis.
Asunto(s)
Bacterias/química , Productos Biológicos/uso terapéutico , Lesiones Traumáticas del Encéfalo/tratamiento farmacológico , Encéfalo/patología , Drosophila melanogaster/fisiología , Tracto Gastrointestinal/patología , Envejecimiento Saludable/efectos de los fármacos , Inflamación/patología , Animales , Productos Biológicos/farmacología , Lesiones Traumáticas del Encéfalo/patología , Drosophila melanogaster/efectos de los fármacos , Tracto Gastrointestinal/efectos de los fármacos , Lacticaseibacillus rhamnosus/fisiología , Longevidad/efectos de los fármacos , Modelos Biológicos , Agregado de Proteínas/efectos de los fármacos , Receptores de Superficie Celular/metabolismoRESUMEN
Aging is a fundamental biological process accompanied by a general decline in tissue function. Indeed, as the lifespan increases, age-related dysfunction, such as cognitive impairment or dementia, will become a growing public health issue. Aging is also a great risk factor for many age-related diseases. Nowadays, people want not only to live longer but also healthier. Therefore, there is a critical need in understanding the underlying cellular and molecular mechanisms regulating aging that will allow us to modify the aging process for healthy aging and alleviate age-related disease. Here, we reviewed the recent breakthroughs in the mechanistic understanding of biological aging, focusing on the adenosine monophosphate-activated kinase (AMPK), Sirtuin 1 (SIRT1) and mammalian target of rapamycin (mTOR) pathways, which are currently considered critical for aging. We also discussed how these proteins and pathways may potentially interact with each other to regulate aging. We further described how the knowledge of these pathways may lead to new interventions for antiaging and against age-related disease.
Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Cognición , Envejecimiento Cognitivo , Envejecimiento Saludable/metabolismo , Transducción de Señal , Sirtuina 1/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Factores de Edad , Animales , Biomarcadores/metabolismo , Cognición/efectos de los fármacos , Activación Enzimática , Activadores de Enzimas/uso terapéutico , Estado Funcional , Envejecimiento Saludable/efectos de los fármacos , Envejecimiento Saludable/psicología , Humanos , Salud Mental , Terapia Molecular Dirigida , Inhibidores de Proteínas Quinasas/uso terapéutico , Transducción de Señal/efectos de los fármacos , Serina-Treonina Quinasas TOR/antagonistas & inhibidoresRESUMEN
Inorganic phosphate (Pi) plays a critical function in many tissues of the body: for example, as part of the hydroxyapatite in the skeleton and as a substrate for ATP synthesis. Pi is the main source of dietary phosphorus. Reduced bioavailability of Pi or excessive losses in the urine causes rickets and osteomalacia. While critical for health in normal amounts, dietary phosphorus is plentiful in the Western diet and is often added to foods as a preservative. This abundance of phosphorus may reduce longevity due to metabolic changes and tissue calcifications. In this review, we examine how dietary phosphorus is absorbed in the gut, current knowledge about Pi sensing, and endocrine regulation of Pi levels. Moreover, we also examine the roles of Pi in different tissues, the consequences of low and high dietary phosphorus in these tissues, and the implications for healthy aging.
Asunto(s)
Huesos/metabolismo , Envejecimiento Saludable/efectos de los fármacos , Fosfatos/farmacocinética , Fósforo Dietético/farmacocinética , Disponibilidad Biológica , HumanosRESUMEN
Aging is physiological and begins very early. It can be accelerated by our lifestyle and by chronic diseases. There are over 300 "theories" of aging and many animal models have been developed ranging from yeast to more complex organisms. Civil age is not a reflection of an individual's physiological age. Starting from the age of 30 a decrease in organ function can be observed. The aging of an individual leads him to 3 states: vigourous, polypathological and dependent or frail. The state of fragility is reversible. We have to be an actor in our aging and no longer suffer it. The centenarians of the blue zones have achieved, culturally, active aging which has led them to successful aging.
TITLE: Vieillissement - Une approche globale, multidimensionnelle et préventive. ABSTRACT: Le vieillissement est un événement physiologique qui commence très tôt dans la vie. L'âge civil, qui nous est donné, ne reflète cependant pas notre âge physiologique. Le vieillissement peut s'accélérer selon nos habitudes de vie. C'est à partir de l'âge de 30 ans que l'on constate une diminution du fonctionnement de nos organes. Le vieillissement conduit ainsi vers 3 états : robuste, polypathologique et dépendant, ou fragile. L'état de fragilité est réversible. Afin de « bien vieillir ¼, il est donc nécessaire d'être acteur de son vieillissement et non plus de le subir. Les centenaires des « zones bleues ¼ qui, culturellement, ont réalisé un vieillissement actif, sont un exemple de vieillissement réussi et donc du « bien vieillir.
Asunto(s)
Envejecimiento/patología , Envejecimiento/fisiología , Medicina Preventiva/métodos , Adulto , Anciano , Anciano de 80 o más Años , Envejecimiento/efectos de los fármacos , Animales , Envejecimiento Saludable/efectos de los fármacos , Envejecimiento Saludable/fisiología , Humanos , Persona de Mediana Edad , Preparaciones Farmacéuticas , Medicina Preventiva/tendenciasRESUMEN
RATIONALE: Malnutrition often affects elderly patients and significantly contributes to the reduction in healthy life expectancy, causing high morbidity and mortality. In particular, protein malnutrition is one of the determinants of frailty and sarcopenia in elderly people. METHODS: To investigate the role of amino acid supplementation in senior patients we performed an open-label randomized trial and administered a particular branched-chain amino acid enriched mixture (BCAAem) or provided diet advice in 155 elderly malnourished patients. They were followed for 2 months, assessing cognitive performance by Mini Mental State Examination (MMSE), muscle mass measured by anthropometry, strength measure by hand grip and performance measured by the Timed Up and Go (TUG) test, the 30 s Chair Sit to Stand (30-s CST) test and the 4 m gait speed test. Moreover we measured oxidative stress in plasma and mitochondrial production of ATP and electron flux in peripheral blood mononuclear cells. RESULTS: Both groups improved in nutritional status, general health and muscle mass, strength and performance; treatment with BCAAem supplementation was more effective than simple diet advice in increasing MMSE (1.2 increase versus 0.2, p = 0.0171), ATP production (0.43 increase versus -0.1, p = 0.0001), electron flux (0.50 increase versus 0.01, p < 0.0001) and in maintaining low oxidative stress. The amelioration of clinical parameters as MMSE, balance, four meter walking test were associated to increased mitochondrial function. CONCLUSIONS: Overall, our findings show that sustaining nutritional support might be clinically relevant in increasing physical performance in elderly malnourished patients and that the use of specific BCAAem might ameliorate also cognitive performance thanks to an amelioration of mitochondria bioenergetics.
Asunto(s)
Aminoácidos de Cadena Ramificada/uso terapéutico , Suplementos Dietéticos , Metabolismo Energético/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Desnutrición/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Estado Nutricional/efectos de los fármacos , Factores de Edad , Anciano de 80 o más Años , Aminoácidos de Cadena Ramificada/efectos adversos , Composición Corporal/efectos de los fármacos , Cognición/efectos de los fármacos , Suplementos Dietéticos/efectos adversos , Femenino , Evaluación Geriátrica , Fuerza de la Mano , Envejecimiento Saludable/metabolismo , Humanos , Italia , Masculino , Desnutrición/diagnóstico , Desnutrición/metabolismo , Desnutrición/fisiopatología , Mitocondrias/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/fisiopatología , Estrés Oxidativo/efectos de los fármacos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Reversing or slowing the aging process brings great promise to treat or prevent age-related disease, and targeting the hallmarks of aging is a strategy to achieve this. Epigenetics affects several if not all of the hallmarks of aging and has therefore emerged as a central target for intervention. One component of epigenetic regulation involves histone deacetylases (HDAC), which include the "classical" histone deacetylases (of class I, II, and IV) and sirtuin deacetylases (of class III). While targeting sirtuins for healthy aging has been extensively reviewed elsewhere, this review focuses on pharmacologically inhibiting the classical HDACs to promote health and longevity. We describe the theories of how classical HDAC inhibitors may operate to increase lifespan, supported by studies in model organisms. Furthermore, we explore potential mechanisms of how HDAC inhibitors may have such a strong grasp on health and longevity, summarizing their links to other hallmarks of aging. Finally, we show the wide range of age-related preclinical disease models, ranging from neurodegeneration to heart disease, diabetes to sarcopenia, which show improvement upon HDAC inhibition.
Asunto(s)
Envejecimiento Saludable/efectos de los fármacos , Inhibidores de Histona Desacetilasas/administración & dosificación , Animales , Evaluación Preclínica de Medicamentos , Epigénesis Genética , Envejecimiento Saludable/metabolismo , Histona Desacetilasas/genética , Histona Desacetilasas/metabolismo , Humanos , Longevidad/efectos de los fármacosRESUMEN
Olive oil is widely accepted as a superior edible oil. Great attention has been given lately to olive oil polyphenols which are linked to significant health beneficial effects. Towards a survey of Greek olive oil focusing on polyphenols, representative extra virgin olive oils (EVOOs) from the main producing areas of the country and the same harvesting period have been collected and analyzed. Significant differences and interesting correlations have been identified connecting certain polyphenols namely hydroxytyrosol, tyrosol, oleacein and oleocanthal with specific parameters e.g. geographical origin, production procedure and cultivation practice. Selected EVOOs polyphenol extracts, with different oleacein and oleocanthal levels, as well as isolated oleacein and oleocanthal were bio-evaluated in mammalian cells and as a dietary supplement in the Drosophila in vivo model. We found that oleocanthal and oleacein activated healthy aging-promoting cytoprotective pathways and suppressed oxidative stress in both mammalian cells and in flies.
Asunto(s)
Aldehídos/farmacología , Antioxidantes/farmacología , Envejecimiento Saludable/efectos de los fármacos , Aceite de Oliva/análisis , Fenoles/farmacología , Polifenoles/farmacología , Aldehídos/aislamiento & purificación , Animales , Antioxidantes/aislamiento & purificación , Línea Celular , Monoterpenos Ciclopentánicos , Drosophila , Grecia , Humanos , Ratones , Olea/química , Fenoles/aislamiento & purificación , Polifenoles/aislamiento & purificaciónRESUMEN
Cellular senescence (CS) is one of hallmarks of aging and accumulation of senescent cells (SCs) with age contributes to tissue or organismal aging, as well as the pathophysiologies of diverse age-related diseases (ARDs). Genetic ablation of SCs in tissues lengthened health span and reduced the risk of age-related pathologies in a mouse model, suggesting a direct link between SCs, longevity, and ARDs. Therefore, senotherapeutics, medicines targeting SCs, might be an emerging strategy for the extension of health span, and prevention or treatment of ARDs. Senotherapeutics are classified as senolytics which kills SCs selectively; senomorphics which modulate functions and morphology of SCs to those of young cells, or delays the progression of young cells to SCs in tissues; and immune-system mediators of the clearance of SCs. Some senolytics and senomorphics have been proven to markedly prevent or treat ARDs in animal models. This review will present the current status of the development of senotherapeutics, in relation to aging itself and ARDs. Finally, future directions and opportunities for senotherapeutics use will discussed. This knowledge will provide information that can be used to develop novel senotherapeutics for health span and ARDs. [BMB Reports 2019; 52(1): 47-55].
Asunto(s)
Envejecimiento/fisiología , Senescencia Celular/fisiología , Envejecimiento Saludable/fisiología , Envejecimiento/efectos de los fármacos , Animales , Senescencia Celular/efectos de los fármacos , Envejecimiento Saludable/efectos de los fármacos , Humanos , Longevidad/fisiología , Ratones , Modelos AnimalesRESUMEN
To follow-up on our previous report that acarbose (ACA), a drug that blocks postprandial glucose spikes, increases mouse lifespan, we studied ACA at three doses: 400, 1,000 (the original dose), and 2,500 ppm, using genetically heterogeneous mice at three sites. Each dose led to a significant change (by log-rank test) in both sexes, with larger effects in males, consistent with the original report. There were no significant differences among the three doses. The two higher doses produced 16% or 17% increases in median longevity of males, but only 4% or 5% increases in females. Age at the 90th percentile was increased significantly (8%-11%) in males at each dose, but was significantly increased (3%) in females only at 1,000 ppm. The sex effect on longevity is not explained simply by weight or fat mass, which were reduced by ACA more in females than in males. ACA at 1,000 ppm reduced lung tumors in males, diminished liver degeneration in both sexes and glomerulosclerosis in females, reduced blood glucose responses to refeeding in males, and improved rotarod performance in aging females, but not males. Three other interventions were also tested: ursolic acid, 2-(2-hydroxyphenyl) benzothiazole (HBX), and INT-767; none of these affected lifespan at the doses tested. The acarbose results confirm and extend our original report, prompt further attention to the effects of transient periods of high blood glucose on aging and the diseases of aging, including cancer, and should motivate studies of acarbose and other glucose-control drugs in humans.