PhD Scientific Days 2025

Molecular Medicine III.

Drug Repurposing to fight aging: in vivo screening of FDA-approved Mitochondrial Enhancers in Caenorhabditis elegans

Előadó neve

Hajdú Gábor, PhD

Neptun code

b7ur4v

Előadó munkahelye

Department of Molecular Biology

Előadó telefonszáma

+36707700697

Előadó e-mail címe

hajdu.gabor-zsolt@semmelweis.hu

Az előadás címe

Drug Repurposing to fight aging: in vivo screening of FDA-approved Mitochondrial Enhancers in Caenorhabditis elegans

Szerző(k) neve és munkahelye

Hajdú Gábor^1,2, Sőti Csaba¹, Alberto Diaz-Ruiz²

1: Department of Molecular Biology, Semmelweis University, Budapest, Hungary
2: IMDEA Food Institute, Madrid, Spain

Bemutatás módja

Szóbeli

Szekció

Molecular Medicine III.

Language of the presentation

English

Preferred session

Molecular Medicine

Összefoglaló szövege

The main goal of cellular longevity research is to understand the molecular biology of age dependent decline and to promote healthy aging and resistance. One particularly important cornerstone of aging is the deterioration of mitochondrial function. Healthy mitochondria are closely related to the healthy energy and metabolic balance of cells, which includes efficient organelle-specific stress responses induced in the event of mitochondrial dysfunction (UPRMITO – Mitochondrial Unfolded Protein Response). Thus, possible treatment by a hormetic substance targeting mitochondria may result in higher resistance to subsequent toxicity, which also affects homeostasis and aging of the entire cell.
We aim to investigate the physiological and molecular effect of an FDA approved homeostatic mitochondrial enhancers employing the roundworm Caenorhabditis elegans as a suitable model in anti-aging drug screening.
Our methodological approach involves healthspan and stress tolerance longevity assays, fluorescence microscopy and qRT-PCR.
Herein we present that chronic exposure to our candidate compound alters physiological performance and longevity of worms. In response to acute treatment, we discovered dose dependent activation of C. elegans stress transcription factors DAF16/ FOXO and HLH30/ TFEB, as well as mRNA expression of candidate target genes responsible for detoxification, UPRMITO and mitophagy. Employing loss-of-function mutants we demonstrate that these gene expression changes were dependent on DAF16/ FOXO and the C. elegans energy sensor AAK2/ AMPK, but not ATFS1, the regulator of UPRMITO. In accordance, acute drug exposure increased AAK-2 and DAF-16 dependent longevity and mitochondria-specific stress tolerance. Finally, we illustrate decline in drug-induced physiological alterations and stress activation in aged worms.
Our findings indicate specific, age-dependent stress and detoxification responses induced by hormetic, acute drug exposure to maintain mitochondrial function. Our work may provide new insights on molecular aspects of FDA-approved compound mechanism of effects, as candidate screen for drug repurposing in preventive medicine and aging research.
This project was funded by EKÖP-2024-2025 New National Excellence Program of the Ministry For Culture and Innovation from the source of the National Research, Development and Innovation.

University

Semmelweis University

Supervisor

Hajdú Gábor

Publication of my abstract

I do not give consent to the publication of my abstract on the website of the congress.

phd.section.field

after finishing doctoral studies with absolutorium (PhD)

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem hagyta jóvá

Előadó

2767

Start

12:00

End

12:15