Department of Laboratory Medicine, Chonnam National University Medical School and Chonnam National University Hwasun Hospital, Jeollanam-do, Korea.
Department of Biomedical Engineering, University of California, CA, USA.
Ann Lab Med. 2018 Sep;38(5):395-401. doi: 10.3343/alm.2018.38.5.395.
Mitochondria are the powerhouses of the cell as well as the primary site of hematopoiesis, which also occurs in the cytoplasm. Hematopoietic stem cells (HSCs) are characterized by a very high turnover rate, and are thus considered to be relatively free from the age-related insults generated by mitochondria. However, HSCs are also subject to these age-related insults, including the incidence of myeloid proliferative diseases, marrow failure, hematopoietic neoplasms, and deterioration of the adaptive human immune system. Recently, NAD⁺ dietary supplements, known as niacin or vitamin B₃, including tryptophan, nicotinic acid, nicotinamide, and the newly identified NAD⁺ precursor nicotinamide riboside, have been shown to play a role in restoring adult stem cell function through the amelioration of mitochondrial dysfunction. This insight motivated a study that focused on reversing aging-related cellular dysfunction in adult mouse muscle stem cells by supplementing their diet with nicotinamide riboside. The remedial effect of nicotinamide riboside enhanced mitochondrial function in these muscle stem cells in a SIRT1-dependent manner, affecting cellular respiration, membrane potential, and production of ATP. Accordingly, numerous studies have demonstrated that sirtuins, under nuclear/mitochondrial control, have age-specific effects in determining HSC phenotypes. Based on the evidence accumulated thus far, we propose a clinical intervention for the restoration of aged HSC function by improving mitochondrial function through NAD⁺ precursor supplementation.
线粒体是细胞的能量工厂，也是造血的主要部位，造血也发生在细胞质中。造血干细胞（HSCs）的特征是具有非常高的周转率，因此被认为相对不受线粒体产生的与年龄相关的损伤的影响。然而，HSCs 也会受到这些与年龄相关的损伤的影响，包括髓系增殖性疾病、骨髓衰竭、造血肿瘤以及适应性人类免疫系统的恶化。最近，NAD⁺膳食补充剂，也称为烟酸或维生素 B₃，包括色氨酸、烟酸、烟酰胺和新发现的 NAD⁺前体烟酰胺核糖，已被证明通过改善线粒体功能在恢复成体干细胞功能方面发挥作用。这一见解促使人们进行了一项研究，即通过在成年小鼠肌肉干细胞的饮食中补充烟酰胺核糖来逆转与衰老相关的细胞功能障碍。烟酰胺核糖的补救作用以 SIRT1 依赖性的方式增强了这些肌肉干细胞中的线粒体功能，影响细胞呼吸、膜电位和 ATP 的产生。因此，许多研究表明，在核/线粒体控制下，沉默调节蛋白在确定 HSC 表型方面具有年龄特异性的影响。基于迄今为止积累的证据，我们提出了一种临床干预措施，即通过 NAD⁺前体补充来改善线粒体功能，从而恢复衰老 HSC 的功能。
