Understanding brain aging for neuroprotective strategies
Aging represents the most important risk factor for the development of neurodegenerative diseases. As life expectancy is increasing and birth rate decreasing, the world’s population is getting older at an unprecedented rate. It is estimated that by 2050, approximately 17% of the global population (1.6 billion) will be aged 65 and over. Unfortunately, the fact that people are living longer has translated into an increase in chronic diseases, including neurodegenerative diseases in the population, with enormous social and economic consequences. Most neurodegenerative conditions for which age constitutes the most important risk factor, including Alzheimer’s disease and Parkinson’s disease, have no cure yet and treatments only modestly decrease symptoms, without a significant delay in the progression of neurodegeneration and the associated functional impairment.
Sagittal section of mouse brain expressing YFP in neurons (green) and stained for a microglial marker in red and cell nuclei in blue.
Searching for novel Geroprotectors
Using in vitro and in vivo models, we study changes in neurons and glial cells along aging. By combining several techniques, including deep proteomic analysis, biomarker detection, microscopy and behavioral analysis, we have discovered the activation of neurodegenerative pathways which can be targeted by genetic and pharmacological approaches. Using biomedical models of brain aging, we have shown that systemic interventions in already aged mice are capable to revert age-associated hippocampal changes, restoring synaptic function, and leading to reversal of learning and memory capacity to youthful levels. In addition to systemic pharmacological interventions, we are also studying the impact of physical activity in brain function, to identify molecular mediators in the muscle-brain axis with neuroprotective effects.
People involved
Macarena Arrazola
PI collaborator
PhD in Biological Sciences from the Catholic University of Chile. Studying the contribution of necroptosis in the age-associated axonal degeneration of the hippocampus, and the impact of using pharmacological approaches to revert neuronal dysfunction and cognitive impairment during aging, proposing necroptosis as an attractive target for the future development of geroprotective tools to treat age-related disabilities.
Daniela Rebolledo
Senior Research Assitant
I am a Biochemist from Pontificia Universidad Católica de Chile (PUC) and PhD in Cell and Molecular Biology from the same university. My PhD thesis research was performed at the Physiology and Biophysics department, University of Washington. My research has focused on the physiology of the neuromuscular system and the pathological mechanisms behind neuromuscular disorders of diverse etiology.
Karina Girardi do Carmo
Postdoctoral fellow
Biologist, Ph.D., and MSc in Cell and Molecular Biology from Oswaldo Cruz Foundation (Fiocruz/RJ). Studying age-dependent decline of regenerative capacity in the peripheral nervous system. Mainly focusing on the contribution of metabolic profile of aging Schwann cells in senescence and particularly exploring the epithelial-mesenchymal transition (EMT) like process.
Felipe Véliz Valverde
PhD Student
Msc Neuroscience. Neurobiology PhD student at Universidad Mayor. I´m interested in understand the beneficial effects of exercise on brain function and behavior in aging. Skeletal muscle can crosstalk with other organs by myokines or exerquines. Some of them can cross the blood brain barrier and reach the brain, triggering neuroprotective effects. The aim question of my work is wheater some exerquines have an effect on axonal degeneration.
David Necuñir
Research Assitant
Biotechnology Engineer and Master from Universidad Nacional Andrés Bello, Santiago de Chile. I’m currently working on the role of necroptosis in axonal degeneration in mesencephalic neurons primary culture, RNA transference and glial cells-neurons communication mediated by exosomes using Schwann cells and evaluating regeneration of peripheral neurons.
Rodrigo Leiva
Research Assitant
B.Sc(hons) degree in Neuroscience from the University of Glasgow and M.Sc in Integrative Neuroscience from the University of Edinburgh. I’m currently working on the role of axonal necroptosis and inflammation in the dopaminergic neurons of the nigrostriatal pathway in Parkinson’s Disease to assess it as a potential therapeutic target through the inhibition of RIPK3.
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