Research Paper Advance Articles
A protective role of SRC-1 against aging associated cognitive decline
- 1 USDA/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
- 2 Jan and Dan Duncan Neurological Research Institute, Texas Children's Hospital, Houston, TX 77030, USA
Received: October 14, 2024 Accepted: July 21, 2025 Published: August 27, 2025
https://doi.org/10.18632/aging.206311How to Cite
Copyright: © 2025 Liu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Introduction: Research indicates a strong correlation between obesity and the risk of dementia, both are linked to steroid receptor coactivator-1 (SRC-1), a transcriptional coactivator.
Methods: We used RNA sequencing analysis (RNA-Seq) to investigate the transcriptome of SRC-1-KO mice, and identified S100 calcium-binding protein A6 (S100A6), an AD associated gene, as one target of SRC-1. We tested cognitive behaviors in SRC-1-KO mice and mice with a humanized SRC-1 mutation (SRC-1L1376P), and performed promoter luciferase assays on S100A6.
Results: Loss of SRC-1 caused alterations in gene signatures that are commonly associated with neurodegenerative diseases, including AD, and diminished the neural plasticity of the hippocampal CA1 neurons. Both SRC-1-KO and SRC-1L1376P mice displayed early signs of contextual memory impairment at 6 months of age. Mechanistically, SRC-1 significantly promoted the expression S100A6.
Conclusion: We identified a protective role of SRC1 against aging associated cognitive decline, potentially by promoting the expression of S100A6.