Stem Cell Institute, James Graham Brown Cancer Center, University of Louisville, 500 South Floyd Street, Rm. 107, Louisville, KY, 40202, USA.
Department of Regenerative Medicine, Warsaw Medical University, Warsaw, Poland.
Stem Cell Rev Rep. 2017 Aug;13(4):443-453. doi: 10.1007/s12015-017-9728-2.
The dream of slowing down the aging process has always inspired mankind. Since stem cells are responsible for tissue and organ rejuvenation, it is logical that we should search for encoded mechanisms affecting life span in these cells. However, in adult life the hierarchy within the stem cell compartment is still not very well defined, and evidence has accumulated that adult tissues contain rare stem cells that possess a broad trans-germ layer differentiation potential. These most-primitive stem cells-those endowed with pluripotent or multipotent differentiation ability and that give rise to other cells more restricted in differentiation, known as tissue-committed stem cells (TCSCs) - are of particular interest. In this review we present the concept supported by accumulating evidence that a population of so-called very small embryonic-like stem cells (VSELs) residing in adult tissues positively impacts the overall survival of mammals, including humans. These unique cells are prevented in vertebrates from premature depletion by decreased sensitivity to growth hormone (GH), insulin (INS), and insulin-like growth factor (IGF) signaling, due to epigenetic changes in paternally imprinted genes that regulate their resistance to these factors. In this context, we can envision nutrient response GH/INS/IGF signaling pathway as a lethal factor for these most primitive stem cells and an important culprit in aging.
延缓衰老过程的梦想一直激励着人类。由于干细胞负责组织和器官的再生，因此我们应该在这些细胞中寻找影响寿命的编码机制，这是合乎逻辑的。然而，在成年期，干细胞群中的层次结构仍未得到很好的定义，并且有证据表明，成年组织中含有罕见的具有广泛跨胚层分化潜力的干细胞。这些最原始的干细胞——那些具有多能或多能分化能力并产生其他分化更受限的细胞的干细胞，被称为组织定向干细胞（TCSCs）——特别令人感兴趣。在这篇综述中，我们提出了一个概念，即越来越多的证据表明，存在于成年组织中的一类所谓的非常小的胚胎样干细胞（VSELs）会对包括人类在内的哺乳动物的整体存活产生积极影响。由于调节其对这些因子抗性的父系印迹基因中的表观遗传变化，这些独特的细胞在脊椎动物中由于对生长激素（GH）、胰岛素（INS）和胰岛素样生长因子（IGF）信号的敏感性降低而免于过早耗尽。在这种情况下，我们可以将营养反应 GH/INS/IGF 信号通路视为这些最原始干细胞的致命因素，也是衰老的重要罪魁祸首。
