选择性药物递送系统通过线粒体重塑抑制脂肪组织衰老代谢研究

Abstract

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.