Neuronal CBP-1 is Required for Enhanced Body Muscle Proteostasis in Response to Reduced Translation Downstream of mTOR.
Front Biosci (Landmark Ed)
; 29(7): 264, 2024 Jul 23.
Article
in En
| MEDLINE
| ID: mdl-39082355
ABSTRACT
BACKGROUND:
The ability to maintain muscle function decreases with age and loss of proteostatic function. Diet, drugs, and genetic interventions that restrict nutrients or nutrient signaling help preserve long-term muscle function and slow age-related decline. Previously, it was shown that attenuating protein synthesis downstream of the mechanistic target of rapamycin (mTOR) gradually increases expression of heat shock response (HSR) genes in a manner that correlates with increased resilience to protein unfolding stress. Here, we investigate the role of specific tissues in mediating the cytoprotective effects of low translation.METHODS:
This study uses genetic tools (transgenic Caenorhabditis elegans (C. elegans), RNA interference and gene expression analysis) as well as physiological assays (survival and paralysis assays) in order to better understand how specific tissues contribute to adaptive changes involving cellular cross-talk that enhance proteostasis under low translation conditions.RESULTS:
We use the C. elegans system to show that lowering translation in neurons or the germline increases heat shock gene expression and survival under conditions of heat stress. In addition, we find that low translation in these tissues protects motility in a body muscle-specific model of proteotoxicity that results in paralysis. Low translation in neurons or germline also results in increased expression of certain muscle regulatory and structural genes, reversing reduced expression normally observed with aging in C. elegans. Enhanced resilience to protein unfolding stress requires neuronal expression of cbp-1.CONCLUSIONS:
Low translation in either neurons or the germline orchestrate protective adaptation in other tissues, including body muscle.Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Protein Biosynthesis
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Caenorhabditis elegans
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Heat-Shock Response
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Caenorhabditis elegans Proteins
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TOR Serine-Threonine Kinases
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Proteostasis
Limits:
Animals
Language:
En
Journal:
Front Biosci (Landmark Ed)
Year:
2024
Document type:
Article
Affiliation country:
United States