PhD Scientific Days 2026

Poster Session 2.M - Neurosciences

Investigating Astrocytic Autophagy During Aging Using Directly Reprogrammed Human-Induced Astrocytes

Name of the presenter

Abbas, Anna

Institute/workplace of the presenter

HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group Institute of Clinical Pathophysiology

Authors

Anna Anoir Abbas¹, Ali Fakhrudin Dadawalla², Julie Bouquety³, Chandramouli Muralidharan⁴, Louis Larin³, Anikó Göblös⁵, Lajos Kemény⁵, Éva Renner⁶, Miklos Palkovits⁶, Janelle Drouin-Ouellet³, Karolina Pircs²
1: HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group Institute of Clinical Pathophysiology
2: HCEMM-SU Neurobiology and Neurodegenerative Diseases Research Group, Institute of Translational Medicine, Semmelweis University, Budapest, Hungary
3: Faculty of Pharmacy, University of Montreal, Montreal, Quebec, Canada
4: Molecular Neurogenetics, Department of Experimental Medical Science, Lund University, Lund, Sweden
5: HCEMM-USZ Skin Research Group, University of Szeged, Szeged, Hungary
6: Human Brain Bank, Semmelweis University, Budapest, Hungary

Text of the abstract

Introduction
Aging is a major risk factor for neurodegenerative diseases, yet the cellular mechanisms underlying human brain aging remain incompletely understood. Astrocytes are essential for maintaining neuronal homeostasis, and age-related impairment of autophagy may contribute to brain dysfunction.

Aims
We aimed to investigate age-related alterations in astrocytic autophagy using a human cell model that preserves donor-specific aging signatures.

Method
Human induced astrocytes (iAs) were directly reprogrammed from dermal fibroblasts obtained from young and aged donors. Autophagy-related changes were assessed by immunocytochemistry and high-content microscopy using the markers LC3, p62, and LAMP1. Starvation was used to induce autophagy, and morphological changes were also analyzed. Transcriptomic observations were used to support the cellular findings.

Results
Aged iAs showed increased LC3 and p62 puncta number and area compared with young iAs, indicating altered autophagy dynamics. LAMP1 changes were donor-dependent, suggesting variability at the lysosomal stage. After starvation, aged iAs displayed increased LC3 puncta size but decreased LAMP1 puncta size, consistent with impaired late-stage autophagic flux. In parallel, aged iAs exhibited a higher aspect ratio, indicating a more reactive astrocyte-like morphology. Autophagy-related parameters significantly correlated with donor age. Transcriptomic analysis further supported age-related disruption of proteostasis-related pathways in astrocytes.

Conclusion
Our findings indicate that astrocytic autophagy is altered during aging and suggest that dysfunctional autophagic flux may contribute to impaired astrocyte homeostasis in the aging human brain. Directly reprogrammed human astrocytes provide a relevant model for studying human brain aging and neurodegeneration.

Funding
Supported by the Cooperative Doctoral Programme (KDP), the SE 250+ Excellence PhD Scholarship, HCEMM, the National Research, Development and Innovation Fund, and Fulbright.