# Molecular mechanisms of translational regulation in aging

> **NIH NIH R01** · BOSTON UNIVERSITY MEDICAL CAMPUS · 2021 · $554,627

## Abstract

Molecular mechanisms of translational regulation in aging
Genome-wide microarray and RNA sequencing studies have revealed changes in the expression of hundreds
of genes during aging in diverse organisms. Transcriptional regulation plays an important role in the control of
gene expression during aging; however, translation efficiency likely plays an equally important role in determining
protein abundance, but has been understudied in this context. Here we propose to study translational changes
that are associated with increased longevity induced by dietary and genetic interventions and examine the mech-
anisms of post-transcriptional gene regulation in aging using yeast as a model system. We will test the hypoth-
esis that, in response to dietary restriction (DR) and genetic alterations that extend lifespan, mRNA-binding pro-
teins (RBPs) coordinately regulate diverse cytoprotective genes by affecting their translation efficiency. To iden-
tify RBPs involved in regulation of these processes, we will apply RNA-Seq and ribosome profiling combined
with next-generation sequencing and characterize transcriptional and translational changes in replicatively aged
yeast cells in response to DR and in a panel of long-lived gene deletion mutants identified in genome-wide
screens. Using the Bayesian network modeling approach, we will integrate transcriptional and translational pro-
filing data with information about transcription factor (TF) binding sites and sequence elements recognized by
RBPs and build a regulatory interaction network. We will then characterize RBPs and directly identify their
mRNA-binding targets. These data will allow us to uncover specific mechanisms and identify cis-regulatory ele-
ments that are responsible for the translational signatures associated with increased longevity. We will also
utilize fluorescence microscopy and cutting-edge microfluidic technologies in order to monitor how the abun-
dance of RBPs changes with age at the single-cell level. Finally, we will use reverse engineering approach to
test if the regulators identified using our systems approach play a causative role in mediating the lifespan exten-
sion through genetic epistasis experiments. Successful completion of this study will add valuable insight into
fundamental principles of translational regulation, and may provide a better understanding of the molecular
mechanisms of aging and lifespan control.

## Key facts

- **NIH application ID:** 10104415
- **Project number:** 5R01AG058713-03
- **Recipient organization:** BOSTON UNIVERSITY MEDICAL CAMPUS
- **Principal Investigator:** Vyacheslav M Labunskyy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $554,627
- **Award type:** 5
- **Project period:** 2019-04-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10104415

## Citation

> US National Institutes of Health, RePORTER application 10104415, Molecular mechanisms of translational regulation in aging (5R01AG058713-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10104415. Licensed CC0.

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