Heterochronic parabiosis is the surgical linking of the circulatory systems of an old individual and young individual, usually mice. The older mouse shows signs of rejuvenation, while the younger mouse shows signs of accelerated aging. There is a robust ongoing process of debate and discovery regarding the mechanisms by which these effects are mediated. At present it appears that a dilution of harmful factors in old blood is likely to account for most of the outcome, but there is evidence for beneficial factors in young blood to be involved. In the study here, researchers show that epigenetic and transcriptomic measures of age are reduced in old mice following heterochronic parabiosis, and that this effect persists for at least a few months following the end of the intervention.
Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on the biological age of organisms and their long-term health remains unknown. Here, we performed extended (3-month) HPB, followed by a 2-month detachment period of anastomosed pairs. Old detached mice exhibited improved physiological parameters and lived longer than control isochronic mice. HPB drastically reduced the biological age of blood and liver based on epigenetic analyses across several clock models on two independent platforms; remarkably, this rejuvenation effect persisted even after 2 months of detachment.
Transcriptomic and epigenomic profiles of anastomosed mice showed an intermediate phenotype between old and young, suggesting a comprehensive multi-omic rejuvenation effect. In addition, old HPB mice showed transcriptome changes opposite to aging, but akin to several lifespan-extending interventions. Altogether, we reveal that long-term HPB can decrease the biological age of mice, in part through long-lasting epigenetic and transcriptome remodeling, culminating in the extension of lifespan and healthspan.