Neuronal DNA repair mediates systemic mitochondrial maintenance through acetylcholine signaling
Abstract
DNA repair defects such as nucleotide excision repair (NER) mutations can lead to progeroid syndromes characterized by growth retardation and accelerated aging with distinct tissue type specific pathologies. DNA-damage-induced dysfunction of specific cell types can impair the organism’s overall function. It is unknown whether, in reverse, DNA repair in specific tissues can have non-cell-autonomous consequences on other tissues carrying DNA damage. To explore the organismal consequences of cell-type-specific DNA repair, we restricted NER activity to specific tissues and monitored consequences on organismal health in Caenorhabditis elegans. Unexpectedly, we observed that tissue-specific DNA repair is sufficient to improve overall DNA damage resistance. Strikingly, NER activity restricted to neurons only is sufficient to provide similar overall DNA damage resistance as whole-body NER in almost all tissues tested. We show that this systemic DNA damage resilience is mediated by neuronal acetylcholine signaling that promotes the maintenance of mitochondrial activity throughout the organism.
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BibTeX
@article{silva2026neuronal,
title = {{Neuronal DNA repair mediates systemic mitochondrial maintenance through acetylcholine signaling}},
author = {Paulo Francisco Lopes da Silva and Baptiste Ropert and Devin Mares and Matthias Rieckher and Corvin Rive and Björn Schumacher},
journal = {Nucleic Acids Research},
year = {2026},
month = oct,
doi = {10.1093/nar/gkag976},
url = {https://doi.org/10.1093/nar/gkag976},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Neuronal DNA repair mediates systemic mitochondrial maintenance through acetylcholine signaling
AU - Paulo Francisco Lopes da Silva
AU - Baptiste Ropert
AU - Devin Mares
AU - Matthias Rieckher
AU - Corvin Rive
AU - Björn Schumacher
PY - 2026
DA - 2026/10/01
JO - Nucleic Acids Research
DO - 10.1093/nar/gkag976
UR - https://doi.org/10.1093/nar/gkag976
AB - DNA repair defects such as nucleotide excision repair (NER) mutations can lead to progeroid syndromes characterized by growth retardation and accelerated aging with distinct tissue type specific pathologies. DNA-damage-induced dysfunction of specific cell types can impair the organism’s overall function. It is unknown whether, in reverse, DNA repair in specific tissues can have non-cell-autonomous consequences on other tissues carrying DNA damage. To explore the organismal consequences of cell-type-specific DNA repair, we restricted NER activity to specific tissues and monitored consequences on organismal health in Caenorhabditis elegans. Unexpectedly, we observed that tissue-specific DNA repair is sufficient to improve overall DNA damage resistance. Strikingly, NER activity restricted to neurons only is sufficient to provide similar overall DNA damage resistance as whole-body NER in almost all tissues tested. We show that this systemic DNA damage resilience is mediated by neuronal acetylcholine signaling that promotes the maintenance of mitochondrial activity throughout the organism.
SN - 0305-1048
SN - 1362-4962
ER -