Introductory Remarks—With Consideration of a T-Cell Model for Aging in Cellular Proteins

In 1947, Henshaw, Riley, and Stapleton first proposed that aging can be caused by alterations in DNA. Unfortunately, they were a decade ahead of their time, for it was not until the early 60’s that attempts were made to resolve the extent to which cellular proteins are vulnerable to aging, and the genetic bases for the changes. One of the driving forces behind this surge of activity was Orgel (1963), who proposed that errors in transcription and translation can bring about senescence through a progressive accumulation of errors in the protein-synthesizing machinery. Although most investigators focused their efforts at the transcriptional and translational levels, a few also considered the effects of aging at the post-translational level, especially after Robinson et al. (1970) observed that deamidation of asparagine and glutamine can cause conformational changes in proteins. Suffice to say, the efforts of the 60’s and 70’s clearly documented that aging at the cellular protein level is complex and heterogenous, and therefore could be polymorphic at the genetic level.