# Age-related transcription stress as novel underlying cause of Alzheimer's disease

> **NIH NIH P01** · ALBERT EINSTEIN COLLEGE OF MEDICINE · 2020 · $286,947

## Abstract

ABSTRACT
Aging is the undisputed main risk factor for onset of Alzheimer disease (AD) and many other dementias, yet is
underinvestigated, because of perceived inability to modify aging. Moreover, aging research is time-
consuming, laborious and expensive. However, we and others have recently made significant advances in
identifying DNA damage as (the) main cause of aging and the ability to accelerate, target and delay aging in
progeroid repair-deficient mouse models for rare human progeroid repair syndromes. These mice show
prominent progressive, bona-fide neurodegeneration exhibiting very strong similarities to human dementias
regarding histopathology, physiology, behavior (loss of cognition, memory, motor performance), neuronal loss
and spontaneous protein aggregation. We also discovered development of transcriptional stress in aged liver
in prematurely and normal aging mice, most likely due to persistent DNA damage interfering with gene
expression. This novel phenomenon in aging leading to imbalanced and reduced transcriptional output could
provide a logical explanation for aging-associated protein aggregation as common denominator in all
proteinopathies including AD. Therefore, we will critically test the hypothesis that human AD suffers from
enhanced transcription stress by analyzing brains of normal and accelerated aging mice and in available
transcriptomics datasets of AD patients to better understand the contribution of aging as the main risk factor for
the onset of neurodegeneration, most notably protein aggregation. This knowledge is a prerequisite for
developing rational-based anti-aging interventions, which prevent or delay progression of AD and other
dementias, addressing a tremendous unmet medical need.

## Key facts

- **NIH application ID:** 10123827
- **Project number:** 3P01AG017242-25S2
- **Recipient organization:** ALBERT EINSTEIN COLLEGE OF MEDICINE
- **Principal Investigator:** JAN VIJG
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $286,947
- **Award type:** 3
- **Project period:** 1999-04-01 → 2024-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10123827

## Citation

> US National Institutes of Health, RePORTER application 10123827, Age-related transcription stress as novel underlying cause of Alzheimer's disease (3P01AG017242-25S2). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/10123827. Licensed CC0.

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