Heterochronic transplantation

Since the 1960s, and perhaps even earlier, researchers have been transplanting tissues and organs from animals of one age to animals of different ages. These “heterochronic” age chimeras have shown rejuvenating properties.

Of the potential rejuvenation therapies that remain to be thoroughly characterized, linking the circulatory systems between a young and old organism – heterochronic parabiosis – is one of the most notable. This surgical procedure has been performed for years on rodents, and it was shown that mouse lifespan could be extended by linking the circulatory system of an old mouse with that of a young mouse. Heterochronic parabiosis was rediscovered as one of the most promising rejuvenation interventions in 2005. By briefly connecting the circulatory system of young and aged mice, old mice exhibited youthful features in the brain, muscle, and liver, characterized by increased cognitive function, replenished stem cell pools, and augmented regenerative capacity.

Following up on this study, researchers have focused on blood components for biological age reversal, while others have investigated the transplantation of other organs to replace aged tissues. With bone marrow transplantation, the blood epigenetic age of the recipients generally matches the age of the donors, although whether this effect is systemic has yet to be established. Of note, bone marrow transplantation has also shown a 12% increase in mouse lifespan.

Additionally, a study using an undisclosed plasma fraction demonstrated robust reversal of epigenetic age, further suggesting that heterochronic transplantation may be a potential rejuvenation intervention. Recent work has also revealed that young splenocyte transplantation ameliorates the aging features of progeroid animals. In addition, transplantation of embryonic brain tissues has shown potential for neuronal repair, and ovarian transplantation was reported to improve health parameters and result in an extended lifespan.