Aging is the pathophysiological process that causes the likelihood of death to increase with advancing age. It can be likened to the wearing out of any machine with time and use. Biologically aging is a consequence of damage to the organism exceeding repair. Peter Medawar posited that this aging process is tolerated after reproduction has occurred, as adverse events after reproduction have little effect on the retention of the causal genes within the gene pool. This effect is called Medawar’s Shadow, the Shadow is the period of time the organism lives after reproduction. This effect explains why damaging genes, such as those for Huntington’s chorea remain in the genome, as the effects of Huntington’s occur after reproduction, it is even thought that some conditions that have adverse effects later in life might increase reproductive success at an earlier stage of life.
The placenta is an unusual organ that is only required for 9 months. It is therefore possible to examine human aging related pathways in a tractable time frame by studying the placenta. Almost all pregnancies have delivered by 40 weeks. Thus the reproductive functions of most placentas have been completed by 40 weeks. We have compared aging related pathways in placentas delivered at 38 weeks with those delivered after 40 weeks. We have identified major changes in the function of the mTOR pathways and in protein synthesis and degradation that occur in the final weeks of pregnancy. It is likely that these aging related changes lead to the rapid increase in stillbirth risks that occur in late gestation.