Proliferation Cycle Causes Age Dependent Mitochondrial Deficiencies and Contributes to the Aging of Stem Cells.
Proliferation Cycle Causes Age Dependent Mitochondrial Deficiencies and Contributes to the Aging of Stem Cells.
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作者：
Ren Q;Zhang F;Xu H
除了时间老化之外，干细胞在成人寿命期间也经历增殖老化。然而，增殖周期的后果及其对干细胞衰老的贡献尚未得到很好的研究。以果蝇雌性生殖系干细胞为模型，我们发现复制周期导致雌性生殖力随年龄而下降，是导致老年雌性后代发育异常的主要因素。增殖性衰老不会导致端粒缩短，但会导致线粒体DNA（mtDNA）控制区突变或重排的积累。我们认为，在衰老干细胞增殖周期的积累所造成的线粒体DNA上的破坏性突变可能会破坏线粒体呼吸链，损害线粒体DNA复制，并代表干细胞衰老的保守机制。
In addition to chronological aging, stem cells are also subject to proliferative aging during the adult life span. However, the consequences of proliferative cycle and their contributions to stem cells aging have not been well investigated. Using Drosophila female germ line stem cells as a model, we found that the replication cycle leads to the age dependent decline of female fecundity, and is a major factor causing developmental abnormalities in the progeny of old females. The proliferative aging does not cause telomere shortening, but causes an accumulation of mitochondrial DNA (mtDNA) mutations or rearrangements at the control region. We propose that damaging mutations on mtDNA caused by accumulation of proliferation cycles in aged stem cells may disrupt mitochondrial respiration chain and impair mtDNA replication and represent a conserved mechanism underlying stem cell aging.
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