Stress-Induced Eukaryotic Translational Regulatory Mechanisms.

The eukaryotic protein synthesis process entails intricate stages governed by diverse mechanisms to tightly regulate translation. Translational regulation during stress is pivotal for maintaining cellular homeostasis, ensuring the accurate expression of essential proteins is important for survival. This selective translational control mechanism is integral to cellular adaptation and resilience under adverse conditions.

Roles of Progranulin and FRamides in Neural Versus Non-Neural Tissues on Dietary Restriction-Related Longevity and Proteostasis in .

Dietary Restriction (DR) mitigates loss of proteostasis associated with aging that underlies neurodegenerative conditions including Alzheimer's disease and related dementias. Previously, we observed increased translational efficiency of certain FMRFamide-Like neuro-Peptide () genes and the neuroprotective growth factor progranulin gene under dietary restriction in . Here, we tested the effects of , , and on lifespan and proteostasis under both standard and dietary restriction conditions.

Neuronal CBP-1 is Required for Enhanced Body Muscle Proteostasis in Response to Reduced Translation Downstream of mTOR.

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.

Stress-induced Eukaryotic Translational Regulatory Mechanisms.

The eukaryotic protein synthesis process entails intricate stages governed by diverse mechanisms to tightly regulate translation. Translational regulation during stress is pivotal for maintaining cellular homeostasis, ensuring the accurate expression of essential proteins crucial for survival. This selective translational control mechanism is integral to cellular adaptation and resilience under adverse conditions.

Neuronal CBP-1 is required for enhanced body muscle proteostasis in response to reduced translation downstream of mTOR.

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.

Roles of progranulin and FRamides in neural versus non-neural tissues on dietary restriction-related longevity and proteostasis in .

Dietary restriction (DR) mitigates loss of proteostasis associated with aging that underlies neurodegenerative conditions including Alzheimer's disease and related dementias. Previously, we observed increased translational efficiency of certain FMRFamide-like neuropeptide ( ) genes and the neuroprotective growth factor progranulin gene under dietary restriction in . Here, we tested the effects of , , and on lifespan and proteostasis under both standard and dietary restriction conditions.

The integrated stress response protects against ER stress but is not required for altered translation and lifespan from dietary restriction in .

The highly conserved integrated stress response (ISR) reduces and redirects mRNA translation in response to certain forms of stress and nutrient limitation. It is activated when kinases phosphorylate a key residue in the alpha subunit of eukaryotic translation initiation factor 2 (eIF2). General Control Nonderepressible-2 (GCN2) is activated to phosphorylate eIF2α by the presence of uncharged tRNA associated with nutrient scarcity, while protein kinase R-like ER kinase-1 (PERK) is activated during the ER unfolded protein response (UPR).

Anabolic Function Downstream of TOR Controls Trade-offs Between Longevity and Reproduction at the Level of Specific Tissues .

As the most energetically expensive cellular process, translation must be finely tuned to environmental conditions. Dietary restriction attenuates signaling through the nutrient sensing mTOR pathway, which reduces translation and redirects resources to preserve the soma. These responses are associated with increased lifespan but also anabolic impairment, phenotypes also observed when translation is genetically suppressed.

A Novel Caenorhabditis Elegans Proteinopathy Model Shows Changes in mRNA Translational Frameshifting During Aging.

Background/aims: Regulation of mRNA translation is central to protein homeostasis and is optimized for speed and accuracy. Spontaneous recoding events occur virtually at any codon but at very low frequency and are commonly assumed to increase as the cell ages.

Methods: Here, we leveraged the polyglutamine(polyQ)-frameshifting model of huntingtin exon 1 with CAG repeat length in the pathological range (Htt51Q), which undergoes enhanced non-programmed translational -1 frameshifting.