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

https://cib.umayor.cl/en/

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.

Cristian Geronimo

Postdoctoral fellow

PhD in Biochemical Sciences from Universidad Nacional Autónoma de México (UNAM). Studying the role of senescent Schwann cells in the failure of nerve regeneration caused by aging or chronic denervation of the peripheral nervous system. Additionally, explore the impact of SASP from senescent Schwann cells on neuronal intrinsic mechanisms.

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.

Francisco Muñoz

PhD Student

Biotechnologist from Universidad Mayor. PhD candidate in Neurobiology at the Center for Integrative Biology (CIB) from Universidad Mayor. Working on the regulating role of aging associated methylation upon mitochondrial stress through the mitochondrial unfolded protein response (UPRmt) and its impact on neurodegeneration and the functionality of the olfactoctory system using Drosophila as a model.

Related Publications

The p75NTR neurotrophin receptor is required to organize the mature neuromuscular synapse by regulating synaptic vesicle availability.

Pérez V, Bermedo-Garcia F, Zelada D, Court FA, Pérez MÁ, Fuenzalida M, Ábrigo J, Cabello-Verrugio C, Moya-Alvarado G, Tapia JC, Valenzuela V, Hetz C, Bronfman FC, Henríquez JP.

Acta Neuropathol Commun. 2019 Sep 12;7(1):147. doi: 10.1186/s40478-019-0802-7.

PMID: 31514753

Read More

c-Jun N-terminal kinase (JNK)-dependent internalization and Rab5-dependent endocytic sorting mediate long-distance retrograde neuronal death induced by axonal BDNF-p75 signaling.

Escudero CA, Cabeza C, Moya-Alvarado G, Maloney MT, Flores CM, Wu C, Court FA, Mobley WC, Bronfman FC.

Sci Rep. 2019 Apr 15;9(1):6070. doi: 10.1038/s41598-019-42420-6.

PMID: 30988348

Read More

Non-canonical function of IRE1α determines mitochondria-associated endoplasmic reticulum composition to control calcium transfer and bioenergetics.

Carreras-Sureda A, Jaña F, Urra H, Durand S, Mortenson DE, Sagredo A, Bustos G, Hazari Y, Ramos-Fernández E, Sassano ML, Pihán P, van Vliet AR, González-Quiroz M, Torres AK, Tapia-Rojas C, Kerkhofs M, Vicente R, Kaufman RJ, Inestrosa NC, Gonzalez-Billault C, Wiseman RL, Agostinis P, Bultynck G, Court FA, Kroemer G, Cárdenas JC, Hetz C.

Nat Cell Biol. 2019 Jun;21(6):755-767. doi: 10.1038/s41556-019-0329-y. Epub 2019 May 20.

PMID: 31110288

Read More

Purification of Exosomes from Primary Schwann Cells, RNA Extraction, and Next-Generation Sequencing of Exosomal RNAs.

De Gregorio C, Díaz P, López-Leal R, Manque P, Court FA.

Methods Mol Biol. 2018;1739:299-315. doi: 10.1007/978-1-4939-7649-2_19.

PMID: 29546715

Read More

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