Blood transfusion/exchange has been believed to exhibit rejuvenation effect since ancient times. Parabiosis is a procedure of placing young blood into an old animal (heterochronic parabiosis) by joining the circulatory systems of the two animals so that they share their blood circulations. The procedure has been reported to bring about an anti-aging effect by specifically activating molecular signaling pathways in liver, muscle, or neural stem cells of the old parabiont resulting in increased tissue regeneration. In search for the physiological background of such rejuvenating effects, certain soluble blood factors have been identified as in part responsible, including the chemokine CCL11, the growth differentiation factor 11 (GDF11), a member of the TGF-β superfamily, and oxytocin. It has been implied that parabiosis reverses age-related decline by targeting several aging hallmarks including stem cell exhaustion, cellular senescence, altered intercellular communication, and inflammaging (Figure ). Still, the mechanisms of action of the factors identified as responsible for the rejuvenating effects in parabiosis animal studies remain largely unclear, with many unresolved issues. Further, a study of the lifespans of old and young rat pairs demonstrated that older partners lived for 4-5 months longer than controls, indicating that circulation of young blood might affect longevity. A start-up company, Alkahestin (Menlo Park, CA, USA), initiated a clinical trial assessing the safety, tolerability, and feasibility of infusion of plasma from young donors to treat patients with mild-tomoderate Alzheimer's disease. The trials implied that the treatment with young fresh frozen plasma has been safe, well tolerated, and feasible. Certain limitations of the study were the small sample size, short duration, and variation in study design, but the conclusion was that the results demand further examination in larger, double-blinded placebo-controlled clinical trials.