Heterochronic parabiosis / Young plasma

Heterochronic parabiosis (HCP) is an experimental surgical technique in which the circulatory systems of a young and an old animal are joined by anastomosis of subcutaneous vasculature, exposing each partner continuously to the other's blood. Classic studies by Clive McCay in the 1950s and a revival by Irina and Michael Conboy (2005, Nature), Amy Wagers, Saul Villeda, and colleagues in the 2000s–2010s showed that old mice conjoined with young partners exhibit improvements in muscle regeneration, neurogenesis, cardiac hypertrophy, and liver function, while young mice show partial deterioration. Two competing mechanistic hypotheses emerged: the young-factors model, proposing that circulating rejuvenating factors in young blood are responsible — highlighted by controversy over GDF11, which was initially championed and then disputed as a beneficial rejuvenation factor — and the dilution model, proposed by Irina Conboy and colleagues, arguing that dilution of pro-aging factors (TGF-β, β2-microglobulin) accumulated in old blood is the dominant mechanism, a view supported by experiments using young saline-albumin exchange rather than young blood specifically. Human translation efforts include Alkahest (spin-out from Villeda's group), which has fractionated plasma into defined protein fractions (GRF6019) for Alzheimer's and Parkinson's trials, and small commercial young-plasma infusion services that preceded regulatory scrutiny; the FDA issued a safety alert in 2019 warning against unproven commercial young-plasma infusions. No plasma-based therapy for aging is currently approved by the FDA or EMA.