RESUMEN
This position statement of the Expert Panel on Brain Health of the American Association for Geriatric Psychiatry (AAGP) emphasizes the critical role of life course brain health in shaping mental well-being during the later stages of life. Evidence posits that maintaining optimal brain health earlier in life is crucial for preventing and managing brain aging-related disorders such as dementia/cognitive decline, depression, stroke, and anxiety. We advocate for a holistic approach that integrates medical, psychological, and social frameworks with culturally tailored interventions across the lifespan to promote brain health and overall mental well-being in aging adults across all communities. Furthermore, our statement underscores the significance of prevention, early detection, and intervention in identifying cognitive decline, mood changes, and related mental illness. Action should also be taken to understand and address the needs of communities that traditionally have unequal access to preventive health information and services. By implementing culturally relevant and tailored evidence-based practices and advancing research in geriatric psychiatry, behavioral neurology, and geroscience, we can enhance the quality of life for older adults facing the unique challenges of aging. This position statement emphasizes the intrinsic link between brain health and mental health in aging, urging healthcare professionals, policymakers, and a broader society to prioritize comprehensive strategies that safeguard and promote brain health from birth through later years across all communities. The AAGP Expert Panel has the goal of launching further activities in the coming months and years.
Asunto(s)
Salud Mental , Calidad de Vida , Humanos , Estados Unidos , Anciano , Psiquiatría Geriátrica , Acontecimientos que Cambian la Vida , EncéfaloRESUMEN
Helping neurons to compensate for proteotoxic stress and maintain function over time (neuronal compensation) has therapeutic potential in aging and neurodegenerative disease. The stress response factor FOXO3 is neuroprotective in models of Huntington's disease (HD), Parkinson's disease and motor-neuron diseases. Neuroprotective compounds acting in a FOXO-dependent manner could thus constitute bona fide drugs for promoting neuronal compensation. However, whether FOXO-dependent neuroprotection is a common feature of several compound families remains unknown. Using drug screening in C. elegans nematodes with neuronal expression of human exon-1 huntingtin (128Q), we found that 3ß-Methoxy-Pregnenolone (MAP4343), 17ß-oestradiol (17ßE2) and 12 flavonoids including isoquercitrin promote neuronal function in 128Q nematodes. MAP4343, 17ßE2 and isoquercitrin also promote stress resistance in mutant Htt striatal cells derived from knock-in HD mice. Interestingly, daf-16/FOXO is required for MAP4343, 17ßE2 and isoquercitrin to sustain neuronal function in 128Q nematodes. This similarly applies to the GSK3 inhibitor lithium chloride (LiCl) and, as previously described, to resveratrol and the AMPK activator metformin. Daf-16/FOXO and the targets engaged by these compounds define a sub-network enriched for stress-response and neuronally-active pathways. Collectively, these data highlights the dependence on a daf-16/FOXO-interaction network as a common feature of several compound families for prolonging neuronal function in HD.
Asunto(s)
Proteínas de Caenorhabditis elegans/genética , Proteína Forkhead Box O3/genética , Factores de Transcripción Forkhead/genética , Proteína Huntingtina/genética , Enfermedad de Huntington/tratamiento farmacológico , Envejecimiento/efectos de los fármacos , Envejecimiento/genética , Animales , Animales Modificados Genéticamente , Caenorhabditis elegans/efectos de los fármacos , Caenorhabditis elegans/genética , Evaluación Preclínica de Medicamentos , Regulación de la Expresión Génica/efectos de los fármacos , Técnicas de Sustitución del Gen , Humanos , Enfermedad de Huntington/genética , Enfermedad de Huntington/patología , Cloruro de Litio/administración & dosificación , Ratones , Neuronas/efectos de los fármacos , Neuronas/patología , Pregnenolona/administración & dosificación , Quercetina/administración & dosificación , Quercetina/análogos & derivadosRESUMEN
The P-type Ca2+ -ATPases are the transporters responsible for calcium homeostasis in the cell compartments of eukaryotes. The KIPMR1 gene of Kluyveromyces lactis encodes a P-type Ca2+ -ATPase, which is functionally and structurally homologous to Pmr1p of Saccharomyces cerevisiae, the calcium pump localized in the Golgi membranes. In this work, a novel involvement of KIPmr1p in cell-wall morphogenesis of K. lactis is reported. KIpmr1delta cells exhibited the loss of outer-chain extension in the glycosylation of secreted proteins. The absence of KIPmr1p resulted in the accumulation of round, large cells with an abnormally thick cell wall, as revealed by transmission electron microscopy. The deletant strain also showed a delocalized deposition of chitin in the lateral cell wall accompanied by an unbalanced ratio of insoluble to soluble glucans. These morphological defects were accompanied by the presence of irregularly shaped nuclei and by a DNA content greater than 2n. Addition of 10 mM Ca2+ to the medium of the KIpmr1delta strain reversed the chitin-deposition impairment, recovered the alteration to the glucan ratio and restored a normal thickness of the cell wall. The mutant cells resumed wild-type size, shape and nuclear morphology but the DNA content indicated the persistence of defects in the co-ordination between DNA replication and cell division. The glycosylation defects were completely unaffected by the calcium supplement. These results indicate that calcium homeostasis controlled by KIPmr1p plays an important role in the cell-wall morphogenesis of K. lactis.