Researchers linked elderly mice with younger mice, resulting in the rejuvenation of the older ones. Is blood the key for eternal youth?
In an unusual experiment conducted by researchers from the US and Russia, the circulatory systems of older and younger mice were connected for a period of 12 weeks. This process slowed down the aging of the older animals’ cells and extended their lifespan by up to 10 percent.
This study builds upon earlier research that suggests the existence of elements in young mammalian blood that warrant further exploration for potential health advantages related to slowing down aging.
While the outcomes appear impressive, they do not adequately support the application of whole-blood transfusions in humans. Apart from the substantial biological differences between mice and humans, there exist numerous well-known and serious risks linked to such treatments for the recipient, not to mention ethical concerns surrounding donation.
Additionally, the duration of twelve weeks in mice could correspond to approximately eight years in humans – a duration that is quite impractical for maintaining a physical connection in a potentially life-threatening manner.
According to James White, a cell biologist from Duke University, the crucial factors driving this phenomenon remain unidentified.
“What holds significance are the components behind this process, and they are yet to be identified,”explained James White.
“Are they proteins or metabolites? Is it the infusion of new cells from the young mouse, or does the young mouse simply alleviate the impact of aging within the older one?”
In order to investigate, Bohan Zhang, a geneticist from Harvard University, and colleagues interconnected the circulatory systems of pairs of young mice (3 months old), pairs of older mice (two years old), and pairs consisting of an older mouse paired with a younger one, and subsequently compared the outcomes.
Tests indicated that the older mice, who received blood from the younger mice, exhibited elevated levels of regulatory compounds such as tricarboxylic acid. This points to chemical processes that are typically disrupted by aging, resulting in increased production of mitochondria (the ‘powerhouses’ of cells), decreased inflammation, and heightened expression of genes linked to extended lifespan.
The research team, in their paper, elucidates that this effect is associated with an extended lifespan, enhanced physiological metrics, and a comprehensive revitalization of genetic regulatory and cellular protein systems on a global scale. They confirm that the circulation of blood for three months between the mice was notably more effective than previously studied shorter-term blood exchanges lasting five weeks.
Simultaneously, while Zhang and colleagues’ study was undergoing peer review, another study utilizing similar techniques was published, delivering unfortunate news concerning the young mice donors. These donors experienced a reduction in their lifespan due to the procedure.
Consequently, the researchers cannot dismiss the possibility that the exchange of entire cells itself prompts these alterations. For instance, this could occur by replacing and diluting the quantity of old damaged cells, subsequently necessitating the donor animal to manage these changes.
Despite this, Zhang and the team were unable to locate any evidence indicating the persistence of the younger cell types in specific locations, such as within the bone marrow, even though the beneficial impacts persisted.
The researchers express a strong interest in identifying the cardiovascular components responsible for these remarkable benefits.
Heterochronic parabiosis (HPB) is known for its functional rejuvenation effects across several mouse tissues. However, its impact on biological age and long-term health is 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 epigenetic age of blood and liver based on several clock models using 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 global multi-omic rejuvenation effect. In addition, old HPB mice showed gene expression changes opposite to aging but akin to several lifespan-extending interventions. Altogether, we reveal that long-term HPB results in lasting epigenetic and transcriptome remodeling, culminating in the extension of lifespan and healthspan.