A new mechanism for aging: chemical "age spots" in immortal DNA strands in distributed stem cells.
The existence of immortal DNA strands (IDSs) in distributed stem cells (DSCs) of adult human tissues was first inferred by Cairns. Cairns deduced the existence of IDSs by connecting two seemingly disparate observations - one his own and the other belonging to Lark. Cairns noted a mathematical discrepancy between predicted human tissue cell mutation rates and human cancer incidence. He integrated this insight with Lark's earlier discovery of non-random mitotic chromosome segregation in both plant root tip cells and mouse fetal fibroblast cultures to predict the existence of IDSs as the essential elements of a mutation-defense mechanism in DSCs. Since Cairns' seminal prediction, several laboratories have identified IDSs in diverse mammalian cells with DSC properties. Past studies focused on the potential roles of IDSs as originally envisioned in DSC genetic fidelity or in the maintenance of the DSC phenotype. Another possible consequence of IDSs, aging, has received little attention. Herein, the potential for cumulative chemical modifications and decompositions (i.e., "age spots") of IDSs in DSCs to act as a major determinant of human aging is considered. If accrued chemical alterations of IDSs prove to be essential determinants of aging, then a means to restore IDSs may yield new strategies for tissue rejuvenation.
Sherley
James L
JL
Boston Biomedical Research Institute, Watertown, MA 02472, USA. sherleyj@bbri.org
D016922:Cellular Senescence / Q000502:physiology*; D020090:Chromosome Segregation; D004261:DNA Replication; D004277:DNA, Single-Stranded; D006801:Humans; D008957:Models, Genetic; D009154:Mutation; D013234:Stem Cells / Q000502:physiology*
D004277:DNA, Single-Stranded