Fight Aging!

Plasma transfer from young to old individuals has produced mixed results in animals and little to no benefit in humans where assessed rigorously. These studies were driven by the hypothesis that young plasma contains meaningfully beneficial factors missing in old plasma, and mixed to poor results suggest that either this hypothesis is untrue, or that plasma transfer is not delivering enough of those beneficial factors. That said, today's open access preprint paper is an example of a plasma transfer study that did manage to produce benefits in old rats. One might well ask what exactly about the experimental procedure is the important difference when compared with earlier exercises. That the treatment was carried out biweekly for the entire remaining life span of the old rats might be one item of interest.

While the paper plays up the idea that factors present in young plasma may be aiding old animals, compelling evidence generated in parabiosis studies and related efforts conducted over the past decade suggests that this is the less plausible mechanism. Dilution of blood via saline and albumin in old animals has produced more robust evidence for health benefits. That one can produce health benefits via simple dilution of blood demonstrates that there are harmful factors present in the aged bloodstream, and sufficient dilution of these factors improves cell and tissue function.

One might consider that failures to achieve results via plasma transfer are examples of failing to produce enough dilution at any given time to significantly change the signaling environment. That doesn't explain the study noted here, of course! The rats were not given enough plasma in any one treatment to produce the level of dilution achieved with saline and albumin in other studies. So what exactly is the difference between successful and unsuccessful plasma transfer animal studies? Contradictory evidence is everywhere in the literature if one looks hard enough, but there is quite a lot of it related to the topic of plasma transfer.

Young Plasma Rejuvenates Blood DNA Methylation Profile, Prolongs Mean Lifespan and Improves Health in Old Rats

There is converging evidence that young blood conveys cells, vesicles, and molecules able to revitalize function and restore organ integrity in old individuals. Here, we assessed the effects of young rat plasma on the lifespan, epigenetic age, and healthspan of old female rats. Beginning at 25.3 months of age, a group of 9 rats (group T) was intraperitoneally injected with plasma from young rats (2 months) until their natural death. A group of control rats of the same age, received no treatment. Blood samples were collected every other week.

Survival curves showed that from age 26 to 30 months, none of the T animals died, whereas the survival curve of C rats began to decline at age 26 months. The external appearance of the T rats was healthier than that of the C counterparts. Blood DNA methylation (DNAm) age versus chronological age showed that DNAm age in young animals increased faster than chronological age then slowed down progressively, entering a plateau after 27 months. Immediately after the start of the treatment, the DNAm age (i.e., epigenetic age) of the treated rats fell below the DNAm age of controls and remained consistently lower until the end of their lives.

Assessment of each experimental group showed that the blood DNA methylation levels of 1638 CpGs were different between treated and control blood samples. Of these, 1007 CpGs exhibited increased methylation, with age while 631 CpGs showed decreased methylation levels. When rats were grouped according to the similarities in their differential blood DNA methylation profile, samples from the treated and control rats clustered in separate groups. Analysis of promoter differential methylation in genes involved in systemic regulatory activities revealed specific gene ontology (GO) term enrichment related to the insulin-like factors (IGFs) pathways as well as to cytokines and chemokines associated with immune and homeostatic functions. We conclude that young plasma therapy may constitute a natural noninvasive intervention for epigenetic rejuvenation and health enhancement, readily translatable to the clinic.