# Regulation of longevity through maintenance of transcription fidelity

> **NIH NIH R01** · BAYLOR COLLEGE OF MEDICINE · 2021 · $325,335

## Abstract

PROJECT SUMMARY
 Aging has profound impacts on the development and progression of human diseases that are principal
causes of mortality, including cardiovascular diseases, diabetes, neurodegenerative diseases, infectious
diseases and cancer. Aberrant epigenetic alterations have been attributed to the development of many age-
related disorders and have recently been found to be closely linked to aging itself. The long-term goal of this
project is to determine the roles of epigenetic and chromatin regulatory pathways in the regulation of aging.
 Recently, through a novel histone mutant lifespan screen, we found that tri-methylation of histone H3 at
lysine 36 (H3K36me3) promotes longevity by suppressing intragenic cryptic transcription. We have also shown
that cryptic transcription, considered a form of transcription infidelity, increases with age in both yeast and
worms; genetic manipulations that suppress cryptic transcription extend lifespan. These observations suggest
that the age-associated increases in cryptic transcription and the resulting loss of transcription fidelity are
evolutionarily conserved causes of aging. In the proposed project, we will test this hypothesis by investigating
1) the cause of increased cryptic transcription during aging; 2) how suppression of cryptic transcription extends
lifespan; and 3) the functional conservation of this pathway during aging in higher eukaryotic systems,
including worms and mammalian adult stem cells. This project examines the molecular causes of aging from a
novel perspective and will lead to the discovery of new epigenetic mechanism of aging that could serve as
potential therapeutic targets of aging and age-related diseases.

## Key facts

- **NIH application ID:** 10150730
- **Project number:** 5R01AG052507-05
- **Recipient organization:** BAYLOR COLLEGE OF MEDICINE
- **Principal Investigator:** Weiwei Dang
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $325,335
- **Award type:** 5
- **Project period:** 2017-09-15 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10150730

## Citation

> US National Institutes of Health, RePORTER application 10150730, Regulation of longevity through maintenance of transcription fidelity (5R01AG052507-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10150730. Licensed CC0.

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