The therapeutic potential of adiponectin and extracellular vesicles for promoting improved healthspan

The gradual decline in physiological functions that comes with aging contributes to a range of chronic diseases, such as Alzheimer's, type 2 diabetes, heart failure, and osteoarthritis. Significant advancements in human longevity due to socioeconomic development have resulted in a foreseeable and substantial strain on the global healthcare system. In fact, there is now a shift in research focus towards enhancing healthspan. As a result, the development of improved therapies for various chronic diseases is essential to enhance healthspan in the aging population. Adiponectin, mainly produced in adipose tissue, is found at elevated levels in the blood of healthy centenarians. In contrast, lower circulating levels of adiponectin are inversely associated with the occurrence and severity of several age-related complications. Adiponectin plays a crucial role in promoting beneficial effects on key biological processes associated with aging-related diseases, contributing to improved healthspan and lifespan in preclinical models. In recent years, extracellular vesicles (EVs) have garnered significant research interest due to their crucial role in both local paracrine signaling and systemic inter-organ communication. They are now widely recognized for their potential as valuable diagnostic and therapeutic tools. In this review, we summarize current knowledge on the pathophysiological roles of adiponectin and EVs in aging, emphasizing their combined therapeutic potential in age-related diseases. Additionally, we explore the emerging evidence of crosstalk between adiponectin and EVs, underscoring their potential for developing improved strategies to promote healthy aging and longevity. • Adiponectin is found at elevated levels in the blood of healthy centenarians and lower circulating levels of adiponectin are inversely associated with the occurrence and severity of several age-related complications. • Adiponectin plays a crucial role in promoting beneficial effects on key biological processes associated with aging-related diseases, contributing to improved healthspan and lifespan in preclinical models. • Extracellular vesicles (EVs) act as important paracrine and endocrine communicators and regulate healthspan. • Both adiponectin and EV are recognized for their potential as valuable diagnostic and therapeutic tools. • We summarize current knowledge on the pathophysiological roles of adiponectin and EV in ageing-associated diseases and emphasize their combined therapeutic potential in modualting healthspan.