There is converging evidence that young blood conveys cells, vesicles and molecules able to revitalize function and restore organ integrity in old individuals. We assessed the effects of young plasma on the lifespan, epigenetic age and healthspan of old female rats. Beginning at 25.6 months of age, a group of 9 rats (group T) was i.p. injected with plasma from young rats until their natural death. A group of 8 control rats of the same age received no treatment (group C). Blood samples were collected every other week. Survival curves showed that from age 26 to 30 months, none of the group T animals died, whereas the survival curve of group C rats began to decline at age 26 months. Blood DNAm age versus chronological age showed that DNAm age in young animals increased faster than chronological age, then slowed down, entering a plateau after 27 months. The DNAm age of the treated rats fell below the DNAm age of controls and, in numerical terms, remained consistently lower until natural death. 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 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.

中文翻译：

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年轻血浆可恢复老年大鼠的血液 DNA 甲基化谱、延长平均寿命并改善其外观

越来越多的证据表明，年轻的血液输送的细胞、囊泡和分子能够使老年人的功能恢复活力并恢复器官的完整性。我们评估了年轻血浆对老年雌性大鼠的寿命、表观遗传年龄和健康寿命的影响。从 25.6 个月大开始，一组 9 只大鼠（T 组）被腹腔注射来自幼鼠的血浆，直到它们自然死亡。一组 8 只同龄对照大鼠不接受任何治疗（C 组）。每隔一周采集一次血样。生存曲线显示，从26月龄到30月龄，T组大鼠均无死亡，而C组大鼠的生存曲线在26月龄时开始下降。血液 DNAm 年龄与实际年龄的比较表明，幼年动物的 DNAm 年龄比实际年龄增长得更快，然后减慢，在 27 个月后进入平台期。接受治疗的大鼠的 DNAm 年龄低于对照组的 DNAm 年龄，并且从数字上看，一直保持较低直至自然死亡。当根据差异血液 DNA 甲基化谱的相似性对大鼠进行分组时，来自治疗组和对照大鼠的样本被分为不同的组。对参与系统调节活动的基因启动子差异甲基化的分析揭示了与胰岛素样因子途径以及与免疫和稳态功能相关的细胞因子和趋化因子相关的特定GO术语富集。我们的结论是，年轻血浆疗法可能构成表观遗传复兴和健康增强的天然非侵入性干预措施。