RESUMEN
The workshop entitled 'Interventions to Slow Aging in Humans: Are We Ready?' was held in Erice, Italy, on October 8-13, 2013, to bring together leading experts in the biology and genetics of aging and obtain a consensus related to the discovery and development of safe interventions to slow aging and increase healthy lifespan in humans. There was consensus that there is sufficient evidence that aging interventions will delay and prevent disease onset for many chronic conditions of adult and old age. Essential pathways have been identified, and behavioral, dietary, and pharmacologic approaches have emerged. Although many gene targets and drugs were discussed and there was not complete consensus about all interventions, the participants selected a subset of the most promising strategies that could be tested in humans for their effects on healthspan. These were: (i) dietary interventions mimicking chronic dietary restriction (periodic fasting mimicking diets, protein restriction, etc.); (ii) drugs that inhibit the growth hormone/IGF-I axis; (iii) drugs that inhibit the mTOR-S6K pathway; or (iv) drugs that activate AMPK or specific sirtuins. These choices were based in part on consistent evidence for the pro-longevity effects and ability of these interventions to prevent or delay multiple age-related diseases and improve healthspan in simple model organisms and rodents and their potential to be safe and effective in extending human healthspan. The authors of this manuscript were speakers and discussants invited to the workshop. The following summary highlights the major points addressed and the conclusions of the meeting.
Asunto(s)
Envejecimiento/efectos de los fármacos , Factores Biológicos/uso terapéutico , Longevidad/efectos de los fármacos , Medicamentos bajo Prescripción/uso terapéutico , Proteínas Quinasas Activadas por AMP/genética , Proteínas Quinasas Activadas por AMP/metabolismo , Envejecimiento/genética , Animales , Restricción Calórica/métodos , Dieta , Activación Enzimática , Regulación de la Expresión Génica , Hormona del Crecimiento/antagonistas & inhibidores , Hormona del Crecimiento/genética , Hormona del Crecimiento/metabolismo , Humanos , Factor I del Crecimiento Similar a la Insulina/antagonistas & inhibidores , Factor I del Crecimiento Similar a la Insulina/genética , Factor I del Crecimiento Similar a la Insulina/metabolismo , Longevidad/genética , Ratones , Proteínas Quinasas S6 Ribosómicas/antagonistas & inhibidores , Proteínas Quinasas S6 Ribosómicas/genética , Proteínas Quinasas S6 Ribosómicas/metabolismo , Transducción de Señal , Sirtuinas/genética , Sirtuinas/metabolismo , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/genética , Serina-Treonina Quinasas TOR/metabolismoRESUMEN
BACKGROUND: Irradiation results in impaired bone healing. Thus, osteosynthesis procedures are afflicted with increased failure rates. To improve osseointegration bone morphogenetic protein-2 (BMP-2) immobilized on nanocrystalline diamond (NCD)-coated implant surfaces might be 1 solution. METHODS: By 4 weeks after irradiation of pig's mandible with a dose of 60 Gy a fracture was accomplished. Osteosynthesis was performed either with titanium osteosynthesis screws or NCD-coated screws with immobilized BMP-2. Nonirradiated animals served as control. After 1, 2, 4, and 8 weeks screws were evaluated histologically. Bone biopsies were gained to extract mesenchymal stem or precursor cells (MSCs). RESULTS: MSCs after irradiation demonstrated a behavior comparable to that of unirradiated cells. Consequently, immobilized BMP-2 resulted in an initial increased bone contact ratio (p = .014) but demonstrated no sustainable effect compared with osseointegration in nonirradiated bone (p = .08). CONCLUSION: Immobilized BMP-2 demonstrates an osteoinductive effect in irradiated bone. MSCs as effector cells possess protective mechanisms to overcome the destructive effect of irradiation.
Asunto(s)
Proteína Morfogenética Ósea 2/farmacología , Tornillos Óseos , Materiales Biocompatibles Revestidos/farmacología , Mandíbula/efectos de la radiación , Fracturas Mandibulares/cirugía , Oseointegración/efectos de los fármacos , Animales , Diamante/farmacología , Modelos Animales de Enfermedad , Fijación de Fractura/instrumentación , Fijación de Fractura/métodos , Curación de Fractura/fisiología , Mandíbula/patología , Mandíbula/cirugía , Fracturas Mandibulares/diagnóstico por imagen , Dosis de Radiación , Radiografía , Distribución Aleatoria , Valores de Referencia , Sensibilidad y Especificidad , Propiedades de Superficie , Sus scrofa , Porcinos , Titanio/farmacologíaRESUMEN
A major goal in the field of aging research is to identify molecular mechanisms of aging at the cellular level, which are anticipated to form the basis for the development of age-associated dysfunctions and diseases in human beings. Recent progress in research into model organisms of aging has allowed determining precise molecular mechanisms and genetic determinants of the aging process, which appear to be conserved in evolution and some of which apply to human aging as well. The consortium of the authors focuses on aging mechanisms at the cellular level, and exploits the potential of genetic analyses in lower eukaryotic model organisms for a better understanding of regulatory pathways implicated in aging processes. We have established a new database (GiSAO), which provides a unique resource for the analysis of genome-wide expression patterns as being regulated by senescence, apoptosis and oxidative stress in our model systems. This has led to the identification of candidate genes, which are being tested for their impact on lifespan regulation in yeast, the fruit fly Drosophila melanogaster and the nematode C. elegans.