Back

Mitochondrial Dysfunction Drives Age-Related Degeneration of the Thoracic Aorta

Dhanekula, A. S.; Harrison, B.; Pharaoh, G.; Mattson-Hughes, A.; Tarantini, S.; Stuppard, R.; DeRoo, S.; Burke, C. R.; Hwang, B.; Pal, J. D.; Mulligan, M. S.; Marcinek, D.

2025-06-15 cell biology
10.1101/2025.06.13.659620 bioRxiv
Show abstract

This study investigated the role of mitochondrial function in aortic aging. As the aorta ages, it becomes stiffer and less compliant, increasing the risk of aneurysmal disease, hypertension, and diastolic dysfunction. Given the role of mitochondrial dysfunction in non-age related aortopathies and as a hallmark of aging, we investigated its contribution to the aging aorta. Both male and female young (5-6 month) and aged (24-25 month) C57Bl/6J mice received mitochondrial-targeted peptide elamipretide (ELAM; SS-31) for 8 weeks. ELAM restored complex II-linked respiration in aged mice to values seen in young mice, while also improving relative phosphorylative flux. ELAM treatment also reduced inflammatory MMP9 expression and elastin breaks in aged mice. Bulk RNAseq analysis revealed that ELAM treatment significantly affected the aortic transcriptome in an age-dependent manner, reducing the expression of senescent and associated pro-inflammatory genes. Mitochondrial dysfunction thus drives aortic aging and is a potential therapeutic target for future study. TeaserLoss of mitochondrial function with age drives degeneration of the aging aorta, and thus is a potential target for therapy.

Matching journals

The top 3 journals account for 50% of the predicted probability mass.

1
GeroScience
○ 109 papers in training set
Top 0.1%
31.5%
Similar papers in this journal
2
Aging Cell
○ 165 papers in training set
Top 0.3%
12.8%
Similar papers in this journal
3
eLife
● 5828 papers in training set
Top 15%
7.4%
Similar papers in this journal
50% of probability mass above
4
PLOS ONE
● 5266 papers in training set
Top 32%
4.1%
Similar papers in this journal
5
American Journal of Physiology-Heart and Circulatory Physiology
● 36 papers in training set
Top 0.3%
3.3%
Similar papers in this journal
6
Journal of the American Heart Association
○ 140 papers in training set
Top 2%
3.3%
7
JCI Insight
● 277 papers in training set
Top 3%
2.7%
8
Aging
○ 75 papers in training set
Top 0.6%
2.1%
9
The FASEB Journal
○ 194 papers in training set
Top 2%
1.9%
10
International Journal of Molecular Sciences
○ 494 papers in training set
Top 8%
1.7%
11
Arteriosclerosis, Thrombosis, and Vascular Biology
○ 71 papers in training set
Top 0.8%
1.5%
12
Frontiers in Aging
○ 11 papers in training set
Top 0.1%
1.5%
13
JACC: Basic to Translational Science
○ 21 papers in training set
Top 0.4%
1.5%
14
Scientific Reports
○ 3612 papers in training set
Top 62%
1.1%
15
Cardiovascular Research
◐ 37 papers in training set
Top 1.0%
1.1%
16
Journal of Molecular and Cellular Cardiology
○ 40 papers in training set
Top 0.6%
1.0%
17
Life Sciences
○ 27 papers in training set
Top 1%
0.9%
18
Matrix Biology Plus
○ 10 papers in training set
Top 0.2%
0.6%
19
npj Regenerative Medicine
○ 24 papers in training set
Top 0.8%
0.6%
20
Biomaterials
○ 84 papers in training set
Top 2%
0.6%
21
Cells
○ 249 papers in training set
Top 8%
0.6%
22
Nature Aging
○ 60 papers in training set
Top 2%
0.6%
23
npj Aging
○ 22 papers in training set
Top 0.5%
0.6%
24
iScience
○ 1154 papers in training set
Top 40%
0.6%
25
Frontiers in Physiology
○ 106 papers in training set
Top 3%
0.6%

"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.