Title : Osmotic remodeling of extracellular vesicles toward targeted longevity therapeutics
Abstract:
Aging is not only driven by the progressive decline of cells and tissues, but also by the spread of biological signals that reinforce dysfunction across the organism. Among these, senescence-associated Extracellular Vesicles (EVs) are emerging as critical mediators of inflammaging and tissue deterioration, acting as carriers of pro-inflammatory factors, altered lipids, pathogenic proteins, and regulatory nucleic acids that can propagate age-related damage beyond the cell of origin. This keynote introduces a new conceptual and technological framework based on the osmotic remodeling of EVs. By exploiting controlled hypo-osmotic stress, EVs can undergo transient swelling, temporary membrane disruption, release of endogenous luminal cargo, and spontaneous membrane reassembly. This process opens the possibility of transforming naturally occurring vesicles from passive carriers of deleterious signals into biologically derived, engineerable platforms for targeted intervention. Within this perspective, osmotic remodeling is presented as a strategy to reduce harmful native cargo while preserving key membrane-associated properties relevant to biological recognition and tissue interaction. Reprogrammed EVs may then serve as adaptable vehicles for the incorporation of selected therapeutic payloads, including regenerative microRNAs, proteins, antioxidants, and modulators of metabolic and inflammatory pathways. Such an approach may support tissue repair, rebalance intercellular communication, and contribute to more precise, biologically informed longevity-oriented interventions.Particular attention is given to the translational value of this platform in the context of precision and personalized longevity medicine, where patient-derived EVs could become a basis for tailored therapeutic design. Rather than relying on fully synthetic delivery systems, this approach envisions the use of endogenous vesicles as customizable carriers with intrinsic biological compatibility and targeting potential.Overall, this talk proposes osmotic remodeling as a paradigm shift in extracellular vesicle engineering: from viewing senescent EVs solely as effectors of aging to considering them as substrates for therapeutic reprogramming. In doing so, it opens a forward-looking perspective at the interface of regenerative medicine, nanomedicine, and targeted longevity therapeutics.
