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Induction and Validation of Cellular Senescence in Primary Human Cells
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Multi-Target Botanical Complex Attenuates Cellular Senescence via Bidirectional P21/P53/SIRT1 Regulation: Dual Model

Jiaqin Wu1, Nanjia Dongzhu2, Chengzhou Zhao2

  • 1College of Pharmacy, Qinghai University, Xining 810016, China.

International Journal of Molecular Sciences
|December 11, 2025
PubMed

Insights

A botanical complex (SBT) combats cellular senescence, a key aging factor. SBT enhances cell viability and antioxidant defenses, offering potential natural interventions for age-related diseases.

Area of Science:

  • Gerontology and cellular biology
  • Natural product chemistry
  • Molecular mechanisms of aging

Background:

  • Cellular senescence is a significant contributor to aging and age-related diseases.
  • Identifying natural compounds with anti-senescence properties is crucial for developing interventions.
  • Existing research highlights the need for understanding the molecular pathways involved in senescence.

Purpose of the Study:

  • To investigate the anti-senescence effects of a multi-component botanical complex (SBT).
  • To elucidate the molecular mechanisms underlying SBT's anti-senescence activity.
  • To evaluate SBT in both in vitro and in vivo aging models.

Main Methods:

  • Utilized D-galactose-induced senescence in H9c2 cardiomyocytes and H2O2-induced accelerated aging in zebrafish.
  • Assessed cell viability and senescence-associated β-galactosidase (SA-β-gal) activity.
  • Analyzed the P21/P53/SIRT1 signaling axis, apoptosis-related genes (Bax, Bcl-2), and antioxidant enzyme activities (SOD, CAT, GSH, MDA).

Main Results:

  • SBT significantly improved cell viability and reduced SA-β-gal activity in senescent cells.
  • SBT demonstrated bidirectional regulation of the P21/P53/SIRT1 axis, downregulating P53/P21 and upregulating SIRT1.
  • SBT enhanced antioxidant capacity in zebrafish by increasing SOD, CAT, and GSH, while decreasing MDA, and modulated apoptosis markers (Bax/Bcl-2).

Conclusions:

  • SBT exhibits potent anti-senescence effects.
  • The mechanisms involve regulating the P21/P53/SIRT1 pathway, boosting antioxidant defense, and inhibiting apoptosis.
  • SBT provides a mechanistic basis for natural product-based anti-aging therapies.
Keywords:
P21/P53/SIRT1 axisapoptosisbidirectional regulationbotanical complexcardiomyocytescellular senescencemulti-targetsenotherapeuticszebrafish model

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