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The Proteasome01:13

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Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
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Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
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The gene expression in cells is regulated at different stages: (i) transcription, (ii) RNA processing, (iii) RNA localization, and (iv) translation. Transcriptional regulation is mediated by regulatory proteins such as transcription factors, activators, or repressors—these control gene expression by initiating or inhibiting the transcription of genes. Once a precursor or pre-mRNA is produced, it undergoes post-transcriptional modification, including 5' capping, splicing, and the...
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A Suppressor Screen for the Characterization of Genetic Links Regulating Chronological Lifespan in Saccharomyces cerevisiae
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Key proteins and pathways that regulate lifespan.

Haihui Pan1, Toren Finkel2

  • 1From the Center for Molecular Medicine, NHLBI, National Institutes of Health, Bethesda, Maryland 20892.

The Journal of Biological Chemistry
|March 8, 2017
PubMed
Summary
This summary is machine-generated.

This review covers key proteins and pathways like sirtuins, insulin/IGF signaling, and mTOR that extend lifespan and healthspan. Understanding these mechanisms could lead to treatments for age-related diseases.

Keywords:
IGF-1aginginsulin-like growth factor (IGF)lifespanmammalian target of rapamycin (mTOR)mouse geneticssirtuinsirtuins

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Area of Science:

  • Gerontology and molecular biology.
  • Focuses on aging processes and molecular mechanisms.
  • Interdisciplinary approach to aging research.

Background:

  • Aging is a complex biological process associated with increased disease risk.
  • Key molecular pathways, including sirtuins, insulin/IGF signaling (IIS), and mechanistic target of rapamycin (mTOR), are implicated in aging.
  • Understanding these pathways is crucial for developing interventions.

Purpose of the Study:

  • To review critical proteins and pathways influencing lifespan and healthspan.
  • To discuss the role of sirtuins, IIS, and mTOR in the aging process across various organisms.
  • To explore the potential for therapeutic interventions targeting aging.

Main Methods:

  • Review of existing scientific literature.
  • Analysis of data from model organisms (e.g., yeast, worms, flies) and mammals (mice, humans).
  • Synthesis of information on protein biology and downstream signaling pathways.

Main Results:

  • Sirtuins, IIS, and mTOR pathways are conserved regulators of aging.
  • These pathways influence the rate of aging across diverse species.
  • Modulation of these pathways shows potential for extending lifespan and healthspan.

Conclusions:

  • Key proteins and pathways offer targets for modulating aging.
  • Targeting sirtuins, IIS, and mTOR may alter aging rates and reduce age-related disease incidence.
  • Rational drug design based on these pathways holds promise for healthy aging.