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Slowed Protein Turnover in Aging Drosophila Reflects a Shift in Cellular Priorities.

ABSTRACT: The accumulation of protein aggregates and dysfunctional organelles as organisms age has led to the hypothesis that aging involves general breakdown of protein quality control. We tested this hypothesis using a proteomic and informatic approach in the fruit fly Drosophila melanogaster. Turnover of most proteins was markedly slower in old flies. However, ribosomal and proteasomal proteins maintained high turnover rates, suggesting that the observed slowdowns in protein turnover might not be due to a global failure of quality control. As protein turnover reflects the balance of protein synthesis and degradation, we investigated whether decreases in synthesis or decreases in degradation would best explain the observed slowdowns in protein turnover. We found that while many individual proteins in old flies showed slower turnover due to decreased degradation, an approximately equal number showed slower turnover due to decreased synthesis, and enrichment analyses revealed that translation machinery itself was less abundant. Mitochondrial complex I subunits and glycolytic enzymes were decreased in abundance as well, and proteins involved in glutamine-dependent anaplerosis were increased, suggesting that old flies modify energy production to limit oxidative damage. Together, our findings suggest that age-related proteostasis changes in Drosophila represent a coordinated adaptation rather than a system collapse.

SUBMITTER: Vincow ES

PROVIDER: S-EPMC8436993 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature

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Slowed Protein Turnover in Aging Drosophila Reflects a Shift in Cellular Priorities.

Vincow Evelyn S ES Thomas Ruth E RE Merrihew Gennifer E GE MacCoss Michael J MJ Pallanck Leo J LJ

The journals of gerontology. Series A, Biological sciences and medical sciences 20210901 10

The accumulation of protein aggregates and dysfunctional organelles as organisms age has led to the hypothesis that aging involves general breakdown of protein quality control. We tested this hypothesis using a proteomic and informatic approach in the fruit fly Drosophila melanogaster. Turnover of most proteins was markedly slower in old flies. However, ribosomal and proteasomal proteins maintained high turnover rates, suggesting that the observed slowdowns in protein turnover might not be due t ...[more]

PMID: 33453098

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Project description:BackgroundIn models extensively used in studies of aging and extended lifespan, such as C. elegans and Drosophila, adult senescence is regulated by gene networks that are likely to be similar to ones that underlie lifespan extension during dormancy. These include the evolutionarily conserved insulin/IGF, TOR and germ line-signaling pathways. Dormancy, also known as dauer stage in the larval worm or adult diapause in the fly, is triggered by adverse environmental conditions, and results in drastically extended lifespan with negligible senescence. It is furthermore characterized by increased stress resistance and somatic maintenance, developmental arrest and reallocated energy resources. In the fly Drosophila melanogaster adult reproductive diapause is additionally manifested in arrested ovary development, improved immune defense and altered metabolism. However, the molecular mechanisms behind this adaptive lifespan extension are not well understood.ResultsA genome wide analysis of transcript changes in diapausing D. melanogaster revealed a differential regulation of more than 4600 genes. Gene ontology (GO) and KEGG pathway analysis reveal that many of these genes are part of signaling pathways that regulate metabolism, stress responses, detoxification, immunity, protein synthesis and processes during aging. More specifically, gene readouts and detailed mapping of the pathways indicate downregulation of insulin-IGF (IIS), target of rapamycin (TOR) and MAP kinase signaling, whereas Toll-dependent immune signaling, Jun-N-terminal kinase (JNK) and Janus kinase/signal transducer and activator of transcription (JAK/STAT) pathways are upregulated during diapause. Furthermore, we detected transcriptional regulation of a large number of genes specifically associated with aging and longevity.ConclusionsWe find that many affected genes and signal pathways are shared between dormancy, aging and lifespan extension, including IIS, TOR, JAK/STAT and JNK. A substantial fraction of the genes affected by diapause have also been found to alter their expression in response to starvation and cold exposure in D. melanogaster, and the pathways overlap those reported in GO analysis of other invertebrates in dormancy or even hibernating mammals. Our study, thus, shows that D. melanogaster is a genetically tractable model for dormancy in other organisms and effects of dormancy on aging and lifespan.

Project description:ObjectivesThe listening demand incurred by speech perception fluctuates in normal conversation. At the acoustic-phonetic level, natural variation in pronunciation acts as speedbumps to accurate lexical selection. Any given utterance may be more or less phonetically ambiguous-a problem that must be resolved by the listener to choose the correct word. This becomes especially apparent when considering two common speech registers-clear and casual-that have characteristically different levels of phonetic ambiguity. Clear speech prioritizes intelligibility through hyperarticulation which results in less ambiguity at the phonetic level, while casual speech tends to have a more collapsed acoustic space. We hypothesized that listeners would invest greater cognitive resources while listening to casual speech to resolve the increased amount of phonetic ambiguity, as compared with clear speech. To this end, we used pupillometry as an online measure of listening effort during perception of clear and casual continuous speech in two background conditions: quiet and noise.DesignForty-eight participants performed a probe detection task while listening to spoken, nonsensical sentences (masked and unmasked) while recording pupil size. Pupil size was modeled using growth curve analysis to capture the dynamics of the pupil response as the sentence unfolded.ResultsPupil size during listening was sensitive to the presence of noise and speech register (clear/casual). Unsurprisingly, listeners had overall larger pupil dilations during speech perception in noise, replicating earlier work. The pupil dilation pattern for clear and casual sentences was considerably more complex. Pupil dilation during clear speech trials was slightly larger than for casual speech, across quiet and noisy backgrounds.ConclusionsWe suggest that listener motivation could explain the larger pupil dilations to clearly spoken speech. We propose that, bounded by the context of this task, listeners devoted more resources to perceiving the speech signal with the greatest acoustic/phonetic fidelity. Further, we unexpectedly found systematic differences in pupil dilation preceding the onset of the spoken sentences. Together, these data demonstrate that the pupillary system is not merely reactive but also adaptive-sensitive to both task structure and listener motivation to maximize accurate perception in a limited resource system.

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Slowed Protein Turnover in Aging Drosophila Reflects a Shift in Cellular Priorities.

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Slowed Protein Turnover in Aging Drosophila Reflects a Shift in Cellular Priorities.

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