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Background <p>Aging is characterized by a progressive decline in physiological function. Among various organs, adipose tissues play an important regulator of systemic metabolism and energy homeostasis. Age-associated alterations in adipose tissue are closely linked to organismal aging. Targeting senescent adipose tissue has therefore emerged as a potential strategy for mitigating age-related dysfunction. The purpose of this study was to develop and evaluate a selective drug delivery system for anti-aging therapy.</p> Results <p>We report a targeted anti-ageing platform based on extracellular vesicles functionalized with the P3 peptide, enabling efficient delivery of dasatinib and quercetin to aged adipose tissue. This platform effectively inhibits senescence-associated secretory phenotype (SASP) in both aged adipocytes and adipose explants in vitro, concomitant with restoration of specific adipocyte function. Furthermore, systemic administration in aged mice contributes to improved physical performance and basal metabolic capacity, alongside attenuation of adipose tissue senescence. Mechanistically, these effects are probably mediated by drug-induced activation of mitophagy and the consequent reprogramming of cellular energy metabolism.</p> Conclusion <p>These findings underscore the pivotal role of adipose tissue in systemic aging processes. The developed delivery platform effectively targets senescent adipose tissue, suppresses SASP, restores physiological function, and enhances organismal physical performance. This work proposes a conceptual framework linking aging and metabolism, offering a promising strategy for organ- or tissue-specific anti-aging interventions.</p> Graphical Abstract <p></p>

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Suppression of senescent metabolism of adipose tissue by rebalancing mitochondrial homeostasis via a selective drug delivery system

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年6月2日

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  • Liwei Wang,
  • Kaicheng Xu,
  • Ziye Guo,
  • Xiaoyong Wu,
  • Di Wang,
  • Liang Chen,
  • Donghua Huang,
  • Kaile Wu,
  • Yubin Zhao,
  • Minjun Yao,
  • Liming Zheng,
  • Xiaobo Yang,
  • Chenyi Ye,
  • Wushi Cui,
  • Wanli Li,
  • An Liu,
  • Mao Zhang,
  • Jianbin Xu

摘要

Background

Aging is characterized by a progressive decline in physiological function. Among various organs, adipose tissues play an important regulator of systemic metabolism and energy homeostasis. Age-associated alterations in adipose tissue are closely linked to organismal aging. Targeting senescent adipose tissue has therefore emerged as a potential strategy for mitigating age-related dysfunction. The purpose of this study was to develop and evaluate a selective drug delivery system for anti-aging therapy.

Results

We report a targeted anti-ageing platform based on extracellular vesicles functionalized with the P3 peptide, enabling efficient delivery of dasatinib and quercetin to aged adipose tissue. This platform effectively inhibits senescence-associated secretory phenotype (SASP) in both aged adipocytes and adipose explants in vitro, concomitant with restoration of specific adipocyte function. Furthermore, systemic administration in aged mice contributes to improved physical performance and basal metabolic capacity, alongside attenuation of adipose tissue senescence. Mechanistically, these effects are probably mediated by drug-induced activation of mitophagy and the consequent reprogramming of cellular energy metabolism.

Conclusion

These findings underscore the pivotal role of adipose tissue in systemic aging processes. The developed delivery platform effectively targets senescent adipose tissue, suppresses SASP, restores physiological function, and enhances organismal physical performance. This work proposes a conceptual framework linking aging and metabolism, offering a promising strategy for organ- or tissue-specific anti-aging interventions.

Graphical Abstract