# Salvianolic acid B attenuates cellular senescence and age-related decline in muscle function via dual mTOR/TP53INP2-autophagy regulation

## TL;DR

Salvianolic acid B reduces signs of aging in cells and improves muscle function in aged mice by regulating key aging pathways.

## Contribution

SAB is shown to attenuate aging via dual regulation of mTOR/TP53INP2-autophagy pathways, both in cells and in vivo.

## Key findings

- SAB reduces SASP, ROS, and enhances ATP production in aging cells.
- SAB improves muscle function in a mouse model of premature aging.
- Transcriptomic analysis links SAB's effects to TP53INP2 upregulation and autophagy activation.

## Abstract

The rapid aging of the global population and the high prevalence of age-related diseases have positioned anti-aging as a critical research priority. Natural products have recently gained significant attention in anti-aging research owing to their multi-target and multi-pathway mechanisms, high safety profiles, and substantial potential for practical ap-plications.

We performed in vitro experiments using aging fibroblasts (BJ) and identified the natural product Salvianolic acid B (SAB) as a potential anti-aging agent, based on its ability to reduce the expression of IL6 and IL1B. Furthermore, we assessed the effects of SAB on cell viability, proliferation, aging-related markers, SASP, ROS levels, and ATP pro-duction. To further investigate the underlying mechanisms of SAB’s anti-aging effects, we utilized network pharmacology and RNA sequencing analyses. In vivo, we used a mouse model of radiation-induced premature aging to evaluate the efficacy of SAB in alleviating age-related decline in muscle function, employing kinematic experiments and histological assessments.

Research has demonstrated that SAB effectively alleviates the cellular senescence phenotype. It was observed that SAB reduces SASP expression through modulation of the mTOR pathway. Additionally, SAB was found to decrease cellular ROS levels and enhance ATP production. In vivo studies further revealed that SAB ameliorates age-related decline in muscle function, potentially through promoting TP53INP2 expression to enhance autophagy. These findings provide novel insights into the potential applications of SAB in the field of anti-aging research.

The study demonstrates that SAB exerts beneficial effects on cellular aging markers, including SASP, ROS, and ATP levels, and alleviates age-related decline in muscle function.

SAB was identified via high-throughput screening as a SASP inhibitor. In senescent cells, it reduced ROS and suppressed SASP. Transcriptomic analysis linked this to TP53INP2 upregulation and autophagy activation. In irradiated mice, SAB improved muscle function, confirming its in vivo efficacy.