Molecular biomarkers of aging: the red cell as a model.

An animal is composed of many cells, tissues, organs, and systems all of which can, and do, age at different rates. The aging process is a summation of unidirectional physical, chemical and biological time-dependent changes, which are not necessarily colinear, hence the potential of asynchrony exists between biological-attributes and chronological age. We have developed two approaches to study the aging of an animal at the cellular and molecular levels. These methods will lend themselves well to distinguish between the effects of this cellular aging on the aging animal, and vice versa; such an interplay is readily apparent. The problem is to demonstrate these correlations in objective terms--not merely to document these changes, but to develop a methodology that also will permit experimental intervention to determine if aging events can be slowed or reversed. These investigations were initiated with the enucleated mammalian RBC in order to study the simplest system (unedited response of a cell). Using flow cytometric procedures as a miniature biochemical laboratory, we thus are able to read the autobiography of the cell as it is debriefed by a series of questions posed. Flow cytometric procedures not only demonstrate the changes, but also monitor their dynamics and kinetics. Concurrently, with these flow cytometric procedures, we are developing 2D-PACE methods to document the changes at the molecular level.