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Related Experiment Video

Updated: May 9, 2025

High-throughput Screening for Chemical Modulators of Post-transcriptionally Regulated Genes
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Identifying Age-Modulating Compounds Using a Novel Computational Framework for Evaluating Transcriptional Age.

Chao Zhang1,2,3, Nathalie Saurat4,5, Daniela Cornacchia4,5

  • 1Section of Computational Biomedicine, Boston University School of Medicine, Boston, Massachusetts, USA.

Aging Cell
|May 1, 2025
PubMed
Summary
This summary is machine-generated.

Researchers developed RNAge, a computational tool to assess cellular aging. This platform identified novel compounds that can induce aging or rejuvenation, aiding in disease modeling and therapeutic development for age-related conditions.

Keywords:
Alzheimer's diseaseage scoreagingcortical neuronsdisease modelinghuman pluripotent stem cellstranscriptional age

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Area of Science:

  • Stem cell biology
  • Computational biology
  • Aging research

Background:

  • Human pluripotent stem cells (hPSCs) offer diverse cell types but typically represent fetal stages.
  • Modeling late-onset diseases requires methods to induce cellular aging in hPSC-derived cells.
  • Existing methods to accelerate aging in hPSC lineages are limited.

Purpose of the Study:

  • Introduce RNAge, a transcriptome-based computational platform for evaluating induced aging and rejuvenation.
  • Validate RNAge across diverse datasets and assess its utility for evaluating age-modulating interventions.
  • Identify novel compounds for inducing aging or rejuvenation in cellular models.

Main Methods:

  • Developed RNAge, a computational platform analyzing transcriptomes to quantify cellular age states.
  • Validated RNAge using independent datasets from various tissues and species.
  • Performed in silico compound screening using the LINCS L1000 dataset and experimental validation.

Main Results:

  • RNAge effectively evaluates induced aging and rejuvenation states and assesses interventions.
  • Identified and confirmed novel compounds that induce aging or rejuvenation in fibroblasts and hPSC-derived neurons.
  • Applying induced aging to an Alzheimer's disease (AD) hPSC model accelerated genotype-specific neurodegeneration.

Conclusions:

  • RNAge provides a robust method for quantifying age-related cellular manipulations.
  • Discovered compounds significantly expand the toolkit for age-modifying strategies in hPSC-derived cells.
  • This approach enhances modeling of age-related diseases, including AD, using stem cell-derived models.