PhD Scientific Days 2026

Poster Session 3.J - Theoretical and Translational Medicine

Neuronal rejuvenation in human derived induced neurons

Name of the presenter

Pillár, Vivien

Institute/workplace of the presenter

Semmelweis University

Authors

Vivien Pillár^1,2, Ágnes Varga¹, Anna Abbas¹, Roland Zsoldos¹, Kinga Vörös¹, Balázs Kis¹, Anikó Göblos³, Lajos Kemény³, Csaba Kerepesi^2,4, István Mándity^5,6, Karolina Pircs^1,2,7
1: HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group, Institute of Clinical Pathophysiology, Semmelweis University
2: HUN-REN-SZTAKI-SU Rejuvenation Research Group
3: HCEMM-Szeged University
4: HUN-REN-SZTAKI BioAgeAI Research Group
5: Semmelweis University, Department of Organic Chemistry
6: HUN-REN Artificial Transporters Research Group
7: Laboratory of Molecular Neurogenetics, Lund University

Text of the abstract

Introduction: Neurodegenerative diseases such as Alzheimer's, Parkinson's and Huntington's disease represent a growing global health burden and are expected to become leading causes of death in developed countries by 2050. As these conditions remain incurable, understanding the molecular mechanisms of neuronal aging, particularly autophagy and synaptic function is essential.
Aims: The aim of this project is to investigate molecular changes associated with neuronal aging in human induced neurons (iNs).
Method: To achieve this, we apply different experimental strategies, including co-culturing neurons derived from young and aged donors to assess whether a youthful cellular environment can promote rejuvenation of aged neurons. In addition, we evaluate the effects of pharmacological compounds targeting ion channel activity and related pathways, as age-associated alterations in ion channel function are thought to contribute to neuronal dysfunction, making them promising candidates for therapeutic intervention. Human fibroblasts from young and aged donors are directly reprogrammed into iNs, preserving their genetic and epigenetic aging characteristics. Cells are labeled using lentiviral constructs expressing mCherry or TagBFP. Mixed cultures are generated to study rejuvenation effects. We use DNA methylation array to determine biological age, while high-content screening microscopy assess neuronal morphology. Pharmacological treatments are applied to examine their impact on aging-related phenotypes.
Results: We expect that mixed cultures may show rejuvenation of aged neurons, reflected in molecular age markers and improved functional properties. These effects will be further characterized by assessing key cellular markers, including p62 and LC3 as indicators of autophagy, mitochondrial level, and LAMP1 as a marker of lysosomal function. Drug treatments may further modulate these processes.
Conclusion: This study provides a human-relevant platform to investigate neuronal aging and supports the identification of therapeutic targets, including ion channel–related mechanisms, contributing to the development of novel treatment strategies.
Funding: This work is supported by the 2025-2.1.1-EKÖP-2025-00014 University Research Scholarship Programme of the Ministry for Culture and Innovation from the source of the National of Research, Development and Innovation Fund.