Korea Nanobiotechnology Center, Pusan National University, Busan 46241, Korea.
Department of Molecular Biology, Pusan National University, Busan 46241, Korea.
Int J Mol Sci. 2020 May 15;21(10):3497. doi: 10.3390/ijms21103497.
Age-related changes in tissue-resident adult stem cells may be closely linked to tissue aging and age-related diseases, such as cancer. β-Hydroxybutyrate is emerging as an important molecule for exhibiting the anti-aging effects of caloric restriction and fasting, which are generally considered to be beneficial for stem cell maintenance and tissue regeneration. The effects of β-hydroxybutyrate on adult stem cells remain largely unknown. Therefore, this study was undertaken to investigate whether β-hydroxybutyrate supplementation exerts beneficial effects on age-related changes in intestinal stem cells that were derived from the midgut. Our results indicate that β-hydroxybutyrate inhibits age- and oxidative stress-induced changes in midgut intestinal stem cells, including centrosome amplification (a hallmark of cancers), hyperproliferation, and DNA damage accumulation. Additionally, β-hydroxybutyrate inhibits age- and oxidative stress-induced heterochromatin instability in enterocytes, an intestinal stem cells niche cells. Our results suggest that β-hydroxybutyrate exerts both intrinsic as well as extrinsic influence in order to maintain stem cell homeostasis.
与组织衰老和年龄相关疾病（如癌症）密切相关的是组织驻留成年干细胞的年龄相关变化。β-羟丁酸作为一种重要的分子，表现出热量限制和禁食的抗衰老作用，这通常被认为有利于干细胞维持和组织再生。β-羟丁酸对成年干细胞的影响在很大程度上尚不清楚。因此，本研究旨在探讨β-羟丁酸补充是否对源自中肠的肠道干细胞的与年龄相关的变化具有有益作用。我们的结果表明，β-羟丁酸抑制了与年龄和氧化应激相关的中肠肠干细胞变化，包括中心体扩增（癌症的标志）、过度增殖和 DNA 损伤积累。此外，β-羟丁酸抑制了与年龄和氧化应激相关的肠细胞中肠干细胞生态位细胞异染色质不稳定。我们的结果表明，β-羟丁酸通过内在和外在的影响来维持干细胞的内稳态。
