PhD Scientific Days 2022

Neurosciences I. (Poster discussion will take place in the Aula during the Coffee Break)

RetaiN: Neuroimmunology and stress resistance in human ageing and neurodegeneration

Text of the abstract

In our aging society there is an urgent need to understand aging, since it affects everyone and it has a great impact on our life and health. Changes of the immune functions and stress-protection pathways are detected in most of the diseases including aging-related disorders, like neurodegeneration. The role and importance of the altered protective mechanisms in these disorders and in general in human aging are still not explored and understood completely. We investigate the immunological and stress-protection-related mechanisms of the neurons in differently aged healthy individuals, using the induced neuron (iN) model. It is a novel tool to investigate human aging by direct reprogramming of fibroblasts into neurons. Uniquely, iNs retain the phenotype, epigenetics and aging signatures of the donor.
Our aim is to gain new insight into the physiology of human aging focusing on neuroimmunological and stress-protection-related mechanisms. The fibroblast cells used in our model are isolated from healthy individuals by skin biopsy. Our cohort consists of 6 young (1-34 years old), 8 middle-aged (41-61 years old) and 10 old (66-85 years old) donors. The isolated fibroblasts have been cultured under standard conditions and transformed into iNs using an “all-in-one” lentiviral vector for transduction. The purity and efficiency of the direct reprogramming have been identified using high-content automated microscopy analysis of MAP2- and TAU-immunolabelled iNs. Further characterization of the differently aged iNs will be done using high content screening, immunocytochemistry, western blot, ELISA, proteomic, transcriptomic and electrophysiological analysis.
With the help of this project we can get closer to understand the role of immune- and stress-protection mechanisms in aging, through which we can identify novel targets to prevent age-related diseases and achieve healthy aging.
Founding: ÚNKP-21, HCEMM, ICGEB, TKP-NVA20