DNA and Aging

As discussed in Chap. 7 , “Generation after generation,” it is apparent that in sexually producing organisms DNA transmitted from generation to generation does much better than the DNA in the mature organism, including ourselves. There is general agreement that natural selection is a declining force after DNA has been passed to the next generation. In old age, there is little selective pressure on genes that do not impact reproductive success. There are several areas of DNA and genomic biology that are important hallmarks of aging, including accumulation of mutations, shortening of telomeres at the end of chromosomes, epigenetic changes, and mitochondrial DNA damage. Given that DNA damage occurs during aging, the more efficient the DNA repair processes the greater the lifespan. While telomere shortening affects cell aging in proliferating cells (such as stem cells), it does not explain aging in nonproliferating differentiated cells. Aging is associated with progressive epigenetic change and can act as a biomarker of aging. Reactive oxygen species (ROS) in mitochondria can cause mtDNA damage, but the amount of DNA damage does not always correlate with aging. Cloning of mature cells has provided new insights into basic aging mechanisms. The involvement of specific genes has come from studies of model organisms such as C. elegans. The involvement of the insulin/IGF-1 signaling (IIS) pathway and the transcription factor FOXO3A in longevity and their relation to dietary restriction is discussed.