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

Abstract

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 i.p 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) was assessed using the HorvathMammalMethylChip320. Blood 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 (q-value<0.05). 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 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.

Reversal of biological age in multiple rat organs by young porcine plasma fraction

“…Detailed values can be found in Supplementary Table S13 Our study presents compelling evidence for epigenetic age reversal in rats via the administration of exosome-containing fraction derived from plasma of young adult pigs. Following our initial report in 2020 [48], additional validation and cross-species evidence affirmed our results [43,[49][50][51]. Mice studies confirmed that young plasma, administered through heterochronic parabiosis, rejuvenated solid organs, reduced epigenetic age by up to 30%, and extended both lifespan and healthspan, with the effect persisting post-separation [50].…”

“…Our results are consistent with the results from a different evaluation of young whole plasma extracted from young rats. In this study, whole plasma from young rats (2 months) was intraperitoneally injected into 25-month-old rats until their natural death [43]. As in the current study, this separate investigation using whole plasma also found that very soon following treatment, the DNAm age of the treated rats fell below that of controls and remained lower until the end of their lives [43].…”

Reversal of Biological Age in Multiple Rat Organs by Young Porcine Plasma Fraction

“…Our study presents compelling evidence for epigenetic age reversal in rats via the administration of exosome-containing fraction derived from plasma of young adult pigs. Following our initial report in 2020 [48], additional validation and cross-species evidence affirmed our results [43,[49][50][51]. Mice studies confirmed that young plasma, administered through heterochronic parabiosis, rejuvenated solid organs, reduced epigenetic age by up to 30%, and extended both lifespan and healthspan, with the effect persisting post-separation [50].…”