Biology of Aging - Antisense Oligonucleotide-Mediated SRF Reduction Ameliorates Mitochondrial Dysfunction in Cardiac Aging - Session 7190 (Poster)

Q: What role does SRF play in cardiac aging according to the study?

SRF is a transcription factor that regulates cardiac integrity, and its elevated expression in aging myocardium worsens mitochondrial dysfunction and heart pathology.

Q: How was SRF reduction achieved in the experimental model?

The study generated a cardiac-specific antisense SRF transgenic mouse model with modestly reduced SRF levels.

Q: What outcomes indicate improvement in mitochondrial health and cardiac aging?

Anti-SRF mice showed reduced hypertrophy and fibrosis, preserved mitochondrial ultrastructure with higher density and cristae, increased mitochondrial DNA copy number, enhanced respiratory complex activity, and reduced oxidative stress markers.

Sep 29, 2026

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Cardiac aging involves progressive mitochondrial dysfunction that contributes to heart failure and other age-related cardiovascular diseases. Serum response factor (SRF), a key transcription factor for cardiac integrity, is elevated in aging myocardium and worsens mitochondrial dysfunction and pathology. This poster evaluates whether antisense oligonucleotide–mediated SRF reduction alleviates mitochondrial dysfunction using a cardiac-specific antisense SRF transgenic mouse model. Results show reduced hypertrophy and fibrosis, improved mitochondrial structure and density, elevated mitochondrial DNA copy number, restored respiratory complex activity, and decreased oxidative stress, supporting SRF reduction as a therapeutic target.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages1

Reading Time3 min

AccessFree to download

Abstract

Study design and model

Key findings: structure, function, and oxidative stress

Conclusion

SESSION 7190 (POSTER) Abstract citation ID: igaf122.2536 BIOLOGY OF AGING I ANTISENSE OLIGONUCLEOTIDE-MEDIATED SRF REDUCTION AMELIORATES MITOCHONDRIAL DYSFUNCTION IN CARDIAC AGING Pankaj Patyal1, Gohar Azhar2, Xiaomin Zhang1, Ambika Verma1, and Jeanne Wei2, 1. University of Arkansas for Medical Sciences, Little Rock, Arkansas, United States, 2. University of Arkansas for Medical Sciences, Little Rock, AR, LITTLE ROCK, Arkansas, United States Cardiac aging is characterized by progressive mitochondrial dysfunction, contributing to heart failure and other age-related cardiovascular diseases. Serum response factor (SRF) is a key transcription factor regulating cardiac integrity, but its elevated expression in aging myocardium worsens mitochondrial dysfunction and heart pathology. This study examines whether antisense oligonucleotide-mediated SRF reduction can alleviate mitochondrial dysfunction in cardiac aging. A cardiac-specific antisense SRF transgenic mouse model with modestly reduced SRF levels was generated. Mice aged 12–15 months were analyzed for cardiac changes, including histology, mitochondrial function, and oxidative stress. Histological analysis revealed reduced cardiac hypertrophy and fibrosis in Anti-SRF Tg mice. Ultrastructural analysis showed well-preserved mitochondrial structure, increased mitochondrial density (p < 0.01), and more cristae (p < 0.01) . Mitochondrial DNA copy number was also higher (p < 0.05). Western blot analysis showed increased expression of mitochondrial regulators PGC-1α (p < 0.01), NT-PGC-1α(p < 0.05), PGC-1β (p< 0.05), and OPA1 (p < 0.05), with reduced Drp1 (p < 0.05) . High-resolution respiratory functional analysis by Oroboros O2K revealed increased activity of mitochondrial complexes I-IV (p < 0.01 to p < 0.001) . This is further corroborated by western blot analyses of OXPHOS (I–V) which shows that SRF reduction resulted in upregulation of mitochondrial complex proteins of electron transport chain. SRF reduction also reduced oxidative stress, indicated by lower 4-HNE levels (p < 0.01) and increased MnSOD expression. In conclusion, cardiac-specific SRF reduction mitigates hypertrophy, fibrosis, mitochondrial dysfunction, and oxidative stress, suggesting its potential as a therapeutic target for cardiac aging.

FAQs

What role does SRF play in cardiac aging according to the study?

SRF is a transcription factor that regulates cardiac integrity, and its elevated expression in aging myocardium worsens mitochondrial dysfunction and heart pathology.

How was SRF reduction achieved in the experimental model?

The study generated a cardiac-specific antisense SRF transgenic mouse model with modestly reduced SRF levels.

What outcomes indicate improvement in mitochondrial health and cardiac aging?

Anti-SRF mice showed reduced hypertrophy and fibrosis, preserved mitochondrial ultrastructure with higher density and cristae, increased mitochondrial DNA copy number, enhanced respiratory complex activity, and reduced oxidative stress markers.

Sep 29, 2026

Upload by Connor