DAF-2/insulin IGF-1 receptor regulates motility during aging by integrating opposite signaling from muscle and neuronal tissues.
daf-2
DAF-16/FOXO
UNC-120/SRF
insulin/IGF-1 signaling
lifespan
mitochondria
motility
oxidative stress
Journal
Aging cell
ISSN: 1474-9726
Titre abrégé: Aging Cell
Pays: England
ID NLM: 101130839
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
revised:
27
05
2022
received:
09
09
2021
accepted:
05
06
2022
pubmed:
10
7
2022
medline:
19
8
2022
entrez:
9
7
2022
Statut:
ppublish
Résumé
During aging, preservation of locomotion is generally considered an indicator of sustained good health, in elderlies and in animal models. In Caenorhabditis elegans, mutants of the insulin-IGF-1 receptor DAF2/IIRc represent a paradigm of healthy aging, as their increased lifespan is accompanied by a delay in age-related loss of motility. Here, we investigated the DAF-2/IIRc-dependent relationship between longevity and motility using an auxin-inducible degron to trigger tissue-specific degradation of endogenous DAF-2/IIRc. As previously reported, inactivation of DAF-2/IIRc in neurons or intestine was sufficient to extend the lifespan of worms, whereas depletion in epidermis, germline, or muscle was not. However, neither intestinal nor neuronal depletion of DAF-2/IIRc prevented the age-related loss of motility. In 1-day-old adults, DAF-2/IIRc depletion in neurons reduced motility in a DAF-16/FOXO dependent manner, while muscle depletion had no effect. By contrast, DAF-2 depletion in the muscle of middle-age animals improved their motility independently of DAF-16/FOXO but required UNC-120/SRF. Yet, neuronal or muscle DAF-2/IIRc depletion both preserved the mitochondria network in aging muscle. Overall, these results show that the motility pattern of daf-2 mutants is determined by the sequential and opposing impact of neurons and muscle tissues and can be dissociated from the regulation of the lifespan. This work also provides the characterization of a versatile tool to analyze the tissue-specific contribution of insulin-like signaling in integrated phenotypes at the whole organism level.
Identifiants
pubmed: 35808897
doi: 10.1111/acel.13660
pmc: PMC9381905
doi:
Substances chimiques
Caenorhabditis elegans Proteins
0
Forkhead Transcription Factors
0
Insulin
0
DAF-2 protein, C elegans
EC 2.7.10.1
Receptor, IGF Type 1
EC 2.7.10.1
Receptor, Insulin
EC 2.7.10.1
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e13660Subventions
Organisme : NIH HHS
ID : P40 OD010440
Pays : United States
Informations de copyright
© 2022 The Authors. Aging Cell published by Anatomical Society and John Wiley & Sons Ltd.
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