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


Retro-Bio says there are things in young blood that are a big part of the effect. Claim they have done very large studies and didn't quite get as good as the Conboy results with just dilution themselves though dilution alone worked good on the muscles and liver. Just like Katcher they wouldn't say what was in the young blood giving the good effects though.

Posted by: Mike Best at August 3rd, 2023 7:42 AM

There was a paper showing that young blood worked, young extracellular vesicles worked but young blood with EV's removed didn't work.

It is looking like the magic is the signaling from the miRNA's and such that are in the young EV's. They directly modify gene expression to that of the younger animal.

Posted by: Lee at August 3rd, 2023 5:21 PM

"Heterochronic blood exchange (HBE) has demonstrated that circulating factors restore youthful features to aged tissues. However, the systemic mediators of those rejuvenating effects remain poorly defined. We show here that the beneficial effect of young blood on aged muscle regeneration was diminished when serum was depleted of extracellular vesicles (EVs). Whereas EVs from young animals rejuvenate aged cell bioenergetics and skeletal muscle regeneration, aging shifts EV subpopulation heterogeneity and compromises downstream benefits on recipient cells. Machine learning classifiers revealed that aging shifts the nucleic acid, but not protein, fingerprint of circulating EVs. Alterations in sub-population heterogeneity were accompanied by declines in transcript levels of the pro-longevity protein, α-Klotho, and injection of EVs improved muscle regeneration in a Klotho mRNA-dependent manner. These studies demonstrate that EVs play a key role in the rejuvenating effects of HBE and that Klotho transcripts within EVs phenocopy the effects of young serum on aged skeletal muscle."

Posted by: Lee at August 3rd, 2023 6:47 PM
Comment Submission

Post a comment; thoughtful, considered opinions are valued. New comments can be edited for a few minutes following submission. Comments incorporating ad hominem attacks, advertising, and other forms of inappropriate behavior are likely to be deleted.

Note that there is a comment feed for those who like to keep up with conversations.