Department of Stem Cell Biology, National Centre for Cell Science, Pune, 411007, India.
Symbiosis Centre for Stem Cell Research, Symbiosis School of Biological Sciences, Symbiosis International University, Pune, 412115, India.
J Tissue Eng Regen Med. 2021 Apr;15(4):388-400. doi: 10.1002/term.3180. Epub 2021 Mar 9.
Aging affects the functionality of hematopoietic stem cells (HSCs), and therefore, aged individuals are not preferred as donors in HSC transplantation. Such elimination leads to the restriction of donor cohort. Several efforts are being done to rejuvenate aged HSCs. Here, we show that treatment of aged mice with curcumin rejuvenates their HSCs by restoring the expression of autophagy-inducing messenger RNAs in them, and improves their engraftment capacity. Importantly, we show that curcumin is effective in rejuvenation of HSCs when administered via both, intraperitoneal as well as oral routes. Aging also affects the immune system. While elderly individuals are not immuno-deficient, they do not respond optimally to immunizations, and hence, a strategy needs to be developed to make them immunologically responsive. Programmed cell death 1 (PD-1), one of the inhibitory coreceptors, plays an important role in the regulation of autoimmunity, infectious immunity, and cancer immunity. Its expression on T cells is indicative of their exhaustion. Here, we show that curcumin reduces the frequency of PD1 cytotoxic T cells in the spleens of aged mice. Curcumin has a proven safety profile, and hence, can be used to treat aged donors to boost the functionality of their HSCs and also to improve the immunological profile of aged individuals. These data could have implications in various other regenerative medicine protocols as well.
衰老会影响造血干细胞(HSCs)的功能,因此,老年个体并不是 HSC 移植中首选的供体。这种排除导致了供体群体的限制。目前正在进行多项努力来使衰老的 HSCs 恢复活力。在这里,我们表明,用姜黄素处理衰老的小鼠可以通过恢复它们中诱导自噬的信使 RNA 的表达来使它们的 HSCs 恢复活力,并提高它们的植入能力。重要的是,我们表明,姜黄素通过腹腔内和口服两种途径给药都可以有效地使 HSCs 恢复活力。衰老也会影响免疫系统。虽然老年人没有免疫缺陷,但他们对免疫接种的反应并不理想,因此需要制定一种策略使他们具有免疫反应性。程序性细胞死亡 1(PD-1)是抑制性共受体之一,在自身免疫、感染免疫和癌症免疫的调节中起着重要作用。其在 T 细胞上的表达表明它们已经衰竭。在这里,我们表明姜黄素可以降低衰老小鼠脾脏中 PD1 细胞毒性 T 细胞的频率。姜黄素具有已证实的安全性,因此可以用于治疗老年供体,以增强其 HSCs 的功能,并改善老年个体的免疫状况。这些数据可能对其他各种再生医学方案也有影响。