Heterochronic Parabiosis Produces Modest Extension of Life in the Older Paired Mouse

Heterochronic parabiosis is the surgical joining of the circulatory systems of an old and young mouse, both of the same genetic background. The younger mouse shows signs of accelerated aging, while the old mouse shows signs of rejuvenation. This has led to a broad range of research and development focused on age-related changes in levels of various signal molecules in the bloodstream. Some groups continue to look at declining levels of specific molecules such as GDF11 and oxytocin that might be boosted in old mice, but at present the consensus appears to be that old blood contains damaging signals, changing cell behavior for the worse. Thus any dilution of those signals is beneficial, whether achieved with young blood or with saline. Here, researchers demonstrate that a few weeks to a few months of parabiosis is enough to modestly extend life span in old mice.

A process of surgically joining the circulatory systems of a young and old mouse slows the aging process at the cellular level and lengthens the lifespan of the older animal by up to 10%. Researchers found that the longer the animals shared circulation, the longer the anti-aging benefits lasted once the two were no longer connected. The findings suggest that the young benefit from a cocktail of components and chemicals in their blood that contributes to vitality, and these factors could potentially be isolated as therapies to speed healing, rejuvenate the body, and add years to an older individual's life.

Earlier studies documented anti-aging benefits in tissues and cells of the older mice after three weeks of parabiosis. These studies found that the older mice became more active and animated, and their tissue showed evidence of rejuvenation. "Our thought was, if we see these anti-aging effects in three weeks of parabiosis, what happens if you bring that out to 12 weeks. That's about 10% of a mouse's lifespan of three years." The ages of the mice were also important, with the young mouse aged four months, and the older mouse aged two years. With follow-up during a two-month detachment period, the older animals exhibited improved physiological abilities and lived 10% longer than animals that had not undergone the procedure.

At the cellular level, parabiosis drastically reduced the epigenetic age of blood and liver tissue, and showed gene expression changes opposite to aging, but akin to several lifespan-extending interventions such as calorie restriction. The rejuvenation effect persisted even after two months of detachment. "The elements that are driving this are what's important, and they are not yet known. Are they proteins or metabolites? Is it new cells that the young mouse is providing, or does the young mouse simply buffer the old, pro-aging blood? This is what we hope to learn next."

Link: https://corporate.dukehealth.org/news/aging-process-slows-when-older-mice-share-circulatory-system-young