Birth and death: Evidence for the same biologic clock.

In mammals, there exists a strong correlation between the average life span (in years) and the length of gestation (in days), suggesting that the same biologic clock mechanisms control both of these physiologic events. Life span is determined by a complex sequence of events leading to organismal senescence, and ultimately death. Although multiple biochemical and cellular phenomena are believed to be involved, progressive telomere shortening due to oxidative stress and loss during DNA replication is believed to be an important determinant contributing to aging, senescence, and adult death. We hypothesize that similar biochemical and cellular phenomena occur in the placenta and fetal membranes resulting in their aging during gestation, their senescence at term, and their apoptotic death resulting in the release of an inflammatory mediator in the form of fetal cell-free DNA. This article reviews the evidence supporting this "telomere gestational clock" hypothesis which proposes that progressive telomere shortening in gestational tissue (especially the placenta and fetal membranes) leads to apoptosis and fetal cell-free DNA release, thereby stimulating the proinflammatory signaling cascade that drives the progression of parturition.