# First Direct Evidence of Accelerated Molecular Aging in Intracranial Aneurysmal Tissue

## TL;DR

This study shows that brain aneurysm tissue ages faster at the molecular level than healthy tissue, with signs like shorter telomeres and increased inflammation.

## Contribution

First direct evidence of accelerated molecular aging in human intracranial aneurysm tissue using telomere length and pathway activation.

## Key findings

- Intracranial aneurysm tissue has significantly shorter telomeres than non-diseased control vessels.
- Aneurysm tissue shows higher oxidative DNA damage and activation of mTOR and NF-κB pathways.
- Lower Lamin B1 and higher P21 expression indicate cellular aging and senescence in aneurysm tissue.

## Abstract

The risk for cardiovascular diseases increases with age. Various markers for vascular aging have been suggested. However, these markers are not a direct measure of aging in vessels. Telomere length quantification can directly measure vascular aging—the current study aimed to investigate aging in aneurysm tissue by quantifying telomere length. Non‐diseased control vessels and ruptured and unruptured intracranial aneurysm vessels were resected during surgery. Telomere length quantification revealed a shorter telomere length in intracranial aneurysm tissue than in the non‐diseased control vessel. The difference in telomere length between non‐diseased control vessels and intracranial aneurysm tissue remained significant after normalizing for age. Moreover, the intracranial aneurysm tissue showed a lower expression of the aging marker Lamin B1 and a higher expression of the senescence marker P21. Additionally, intracranial aneurysm tissue presented higher activation of mTOR and NF‐κB pathways, which are known to contribute to inflammation and aging. Oxidative stress‐induced DNA damage appeared higher in intracranial aneurysm tissue than in non‐diseased control vessels. Our human data clearly showed increased molecular aging, elevated oxidative stress, and the activation of aging and inflammation‐associated pathways NF‐κB and mTOR in intracranial aneurysm tissue compared to non‐diseased control vessels.

This study provides the first direct evidence of accelerated molecular aging in human intracranial aneurysm tissue, marked by telomere shortening, oxidative DNA damage, and activation of mTOR and NF‐κB pathways. These findings reveal critical aging‐related mechanisms potentially driving aneurysm formation and rupture.