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Related Concept Videos

What is Gene Expression?01:42

What is Gene Expression?

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Overview
Gene expression is the process in which DNA directs the synthesis of functional products, that is, proteins. Cells can regulate gene expression at various stages. It allows organisms to generate different cell types and enables cells to adapt to internal and external factors.
Genetic Information Flows from DNA to RNA to Protein
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Multicellular organisms contain a variety of structurally and functionally distinct cell types, but the DNA in all the cells originated from the same parent cells. The differences in the cells can be attributed to the differential gene expression. Liver cells, whose functions include detoxification of blood, production of bile to metabolize fats, and synthesis of proteins essential for metabolism, must express a specific set of genes to perform their functions. Gene expression also varies with...
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mRNA Stability and Gene Expression02:51

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The structure and stability of mRNA molecules regulates gene expression, as mRNAs are a key step in the pathway from gene to protein. In eukaryotes, the half-life of mRNA varies from a few minutes up to several days. mRNA stability is essential in growth and development. The absence of the proteins regulating its stability, such as tristetraprolin in mice, can cause systemic issues, including bone marrow overgrowth, inflammation, and autoimmunity.
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Drug Repurposing Hypothesis Generation Using the "RE:fine Drugs" System
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Gene expression-based drug repurposing to target aging.

Handan Melike Dönertaş1, Matías Fuentealba Valenzuela1,2, Linda Partridge2,3

  • 1European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK.

Aging Cell
|July 1, 2018
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Summary
This summary is machine-generated.

This study used a systems-level drug repurposing approach to identify drugs combating aging in the human brain. Researchers found 24 drugs that may reverse aging effects or mimic cellular defenses, offering new avenues for longevity research.

Keywords:
agingdrug repurposinggene expressionthe Connectivity Map

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Area of Science:

  • Gerontology and Pharmacology
  • Neuroscience and Computational Biology

Background:

  • Aging is the primary risk factor for numerous noncommunicable diseases.
  • Genetic and chemical interventions in model organisms can extend lifespan and healthspan.
  • Aging's complexity and interacting mechanisms challenge the discovery of anti-aging drugs.

Purpose of the Study:

  • To discover drugs that combat aging in the human brain using a systems-level drug repurposing methodology.
  • To identify pharmacological candidates by analyzing age-related gene expression changes in human brain tissue.
  • To move beyond target-centric approaches by employing a data-driven, systems-level strategy.

Main Methods:

  • Utilized multiple human brain gene expression datasets from individuals of varying ages.
  • Identified gene expression patterns characteristic of aging.
  • Compared aging-associated gene expression changes with drug-perturbed profiles in the Connectivity Map database.

Main Results:

  • Identified 24 drugs significantly associated with age-related gene expression changes.
  • Discovered drugs that may reverse detrimental aging effects or mimic cellular defense mechanisms.
  • Validated the approach by finding known prolongevity drugs among the identified candidates, suggesting de novo drug discovery potential.

Conclusions:

  • The systems-level drug repurposing approach effectively identifies potential anti-aging drugs for the human brain.
  • This unbiased methodology, using human brain aging data, focuses on relevant biological processes.
  • The findings open possibilities for discovering novel therapeutic targets for aging and age-related diseases.