Epigenetic drift in aging identical twins

Those of you, like this author, who have managed to stay alive for close to eight decades or more, will have had the experience of observing increasing degrees of phenotypic discordances among our identical twin friends as we age together. They may succumb to the same disease, but often the age of onset is years or even decades apart. An interesting example is a report of twins, both of whom developed histologically confirmed dementia of the Alzheimer's type; one had the diagnosis in her late 60s but the other was not diagnosed until age 83 (1). The conventional wisdom is that the bulk of these differences can be attributable to good or bad luck with one's environmental exposures, to the quality of medical and spousal care (or abuse), or to learned behavioral differences in how we exercise (perhaps mentally and physically) and what we eat, drink, or smoke, among myriad other possibilities. Many have assumed that, apart from some rare point mutations or aberrant chromosomal segregations and their impacts upon the emergence of neoplastic diseases, the differences we see are not due to heritable changes in cells. There is growing interest, however, in that class of potentially heritable change in DNA that is not associated with alterations in the primary nucleotide sequence or copy number but rather is modulated by what Joshua Lederberg (2) long ago referred to as “epinucleic.” Modern molecular genetics now points to two major classes of such alterations: methylations of cytosine at cytosine-guanine dinucleotides and covalent modifications of DNA-bound histones, notably acetylations and methylations. Cytosine methylations at regions of gene promoters rich in CpG …