Clonal Attenuation of Somatic Cells in Aging Mammals: A Review of Supportive Evidence and Its Biomedical SignificanceClonal Attenuation of Somatic Cells in Aging Mammals: A Review of Supportive Evidence and Its Biomedical Significance

摘要

Clonal attenuation can be defined as the gradual depletion of the replicative potentials of individual clones of mammalian somatic cells. Publications from the author's laboratory and from other laboratories are reviewed that support the proposition that clonal attenuation is a continuous process throughout the life course and that it occurs in vivo in primates. The puzzling discordance between the mass culture results from the laboratories of the late Vincent Cristofalo (tissue from living subjects) and those from the Martin laboratory (tissue predominately from autopsy subjects) is discussed. Finally, the implications of clonal attenuation and replicative senescence, for such major age-related pathologic processes as neoplasia, atherosclerosis, benign prostatic hy-perplasia, and osteoarthritis, are addressed; these and other disorders of aging can be characterized as a mixture of atrophy and hyperplasia, presumably related to a failure of homeostatic cell-cell interactions in aging tissues. For the case of neoplasia, an argument can be made that such failures precede what is increasingly regarded as the most critical step in carcinogenesis-the evolution of a mutator phenotype.