Plasma-Based Strategies for Therapeutic Modulation of Brain Aging

Age is the primary risk factor for the vast majority of disorders, including neurodegenerative diseases impacting brain function. Whether the consequences of aging at the biological level can be reversed, or age-related changes prevented, to change the trajectory of such disorders is thus of extreme interest and value. Studies using young plasma, the acellular component of blood, have demonstrated that aging is malleable, with the ability to restore functions in old animals. Fascinatingly, this functional improvement is even observed in the brain, despite the blood-brain barrier, indicating that peripheral sources can effectively impact central sites leading to clinically relevant changes such as enhancement of cognitive function. A plasma-based approach is also attractive as aging is inherently complex, with an array of mechanisms dysregulated in diverse cells and organs throughout the body leading to disturbed function. Plasma, containing a natural mixture of components, has the ability to act multimodally, modulating diverse mechanisms that can converge to change the trajectory of age-related diseases. Here we review the evidence that plasma modulates aging processes in the brain and consider the therapeutic applications that derive from these observations. Plasma and plasma-derived therapeutics are an attractive translation of this concept, requiring critical consideration of benefits, risks, and ethics. Ultimately, knowledge derived from this science will drive a comprehensive molecular understanding to deliver optimized therapeutics. The potential of highly differentiated, multimodal therapeutics for treatment of age-related brain disorders provides an exciting new clinical approach to address the complex etiology of aging.