# Project 3 - Defining the role of ribosome protein composition in regulating the selective translation of pro-longevity genes

> **NIH NIH P20** · MOUNT DESERT ISLAND BIOLOGICAL LAB · 2020 · $293,315

## Abstract

PROJECT 3 (Rollins) PROJECT SUMMARY
 Aging is the primary risk factor for numerous prevalent chronic conditions and diseases, including
cancer, neurodegeneration, and cardiovascular disease. It is estimated that age-associated diseases cost the
U.S. >$302 billion a year in healthcare expenditures. Slowing the rate of aging would increase the healthy
years of life and simultaneously prevent or delay age-associated diseases.
 The last forty years has seen a revolution in our understanding of the biology of aging and the
realization that aging can be manipulated genetically and environmentally. It has been well established in
multiple invertebrate and vertebrate animal models that exposure to mild stressors such as caloric restriction
(CR) protects against age-related diseases and increases healthy longevity. CR is known to activate the
expression of pro-longevity genetic pathways. However, the mechanisms by which CR modulates pro-
longevity gene expression are incompletely understood.
 Our recent studies in the genetic model organism C. elegans demonstrated for the first time that CR
modulates the translation of various pro-longevity genes without affecting their transcription. Protein
translation is mediated by the ribosome, a molecular machine comprised of up to 79 ribosomal proteins. While
once considered static, the protein composition of the ribosome can vary. These compositional changes in turn
can alter how specific mRNAs are selected for translation.
 We have shown recently that CR regulates the expression of ribosomal proteins in C. elegans.
Knockdown in well-fed C. elegans of ribosomal proteins that are downregulated during CR mimics the effects
of CR on longevity. Transcriptomic and proteomic data in humans, mice, fruit fly, yeast, and C. elegans have
demonstrated that expression of ribosomal proteins is selectively altered with age. Taken together, these data
suggest that regulated changes in ribosome composition may mediate the effects of CR on the translation of
pro-longevity genes and the associated increase in lifespan.
 The overarching goal of this proposal is to begin defining how ribosome protein composition
modulates mRNA translation and associated changes in health and longevity. Studies outlined in this
proposal will test the hypothesis that changes in ribosomal protein composition associated with CR regulate
longevity by modulating the translation of specific mRNAs. Our studies will also test the hypothesis that CR
prevents age-related changes in ribosome protein composition and that this promotes the selective translation
of pro-longevity genes. Detailed understanding of the molecular mechanisms by which CR modulates
longevity is critical to understanding the aging process and for developing therapies that slow the onset and
progression of age-related diseases in humans.

## Key facts

- **NIH application ID:** 9937751
- **Project number:** 5P20GM104318-08
- **Recipient organization:** MOUNT DESERT ISLAND BIOLOGICAL LAB
- **Principal Investigator:** Jarod Alton Rollins
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $293,315
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9937751

## Citation

> US National Institutes of Health, RePORTER application 9937751, Project 3 - Defining the role of ribosome protein composition in regulating the selective translation of pro-longevity genes (5P20GM104318-08). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/9937751. Licensed CC0.

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