Van Zant Gary, Liang Ying
Department of Internal Medicine, University of Kentucky, Lexington, Ky, USA.
Exp Hematol. 2003 Aug;31(8):659-72. doi: 10.1016/s0301-472x(03)00088-2.
The objectives of this review were first to critically review what is known about the effects of aging on stem cells in general, and hematopoietic stem cells in particular. Secondly, evidence is marshalled in support of the hypothesis that aging stem cells play a critical role in determining the effects of aging on organ function, and ultimately on the lifespan of a mammal. Aging has both quantitative and qualitative effects on stem cells. On balance, the qualitative changes are the more important since they affect the self-renewal potential, developmental potential, and interactions with extrinsic signals, including those from stroma. Although hematopoiesis is generally maintained at normal and life-supporting levels during normal aging, diminished function is acutely apparent when old stem cells are subjected to stress. There is ample evidence of diminished self-renewal capacity, restriction of the breadth of developmental potency, and decreased numbers of progeny of old stem cells subjected to hematopoietic demands. The prediction is made that whatever plasticity in developmental potential possessed by a young stem cell is lost during aging. Those parts of the world enjoying an ever-increasing standard of living are also inhabited by an increasingly elderly population. The effects of age on many physiological functions are not well studied or appreciated. A public health challenge to provide increased quality of life for this growing segment of the population requires more attention to the variable of age in experimental studies. Stem cell populations are likely to be a fruitful subject for studies of this type.
本综述的目的首先是批判性地审视关于衰老对一般干细胞，尤其是造血干细胞影响的已知情况。其次，整理证据以支持以下假说：衰老的干细胞在决定衰老对器官功能以及最终对哺乳动物寿命的影响方面起着关键作用。衰老对干细胞既有数量上的影响，也有质量上的影响。总体而言，质量上的变化更为重要，因为它们会影响自我更新潜能、发育潜能以及与外部信号（包括来自基质的信号）的相互作用。虽然在正常衰老过程中造血功能通常维持在正常且维持生命的水平，但当衰老的干细胞受到应激时，功能下降就会明显显现。有充分证据表明衰老干细胞的自我更新能力下降、发育潜能的广度受限，以及在造血需求下衰老干细胞的子代数量减少。据预测，年轻干细胞所具有的任何发育潜能可塑性在衰老过程中都会丧失。世界上生活水平不断提高的地区，老年人口也在日益增加。年龄对许多生理功能的影响尚未得到充分研究和认识。为这一不断增长的人口群体提高生活质量所面临的公共卫生挑战，需要在实验研究中更多地关注年龄变量。干细胞群体可能是这类研究的一个富有成果的主题。
