Principles of control and selection in mammalian aging.

Acquisition of immunologic self-tolerance by clonal deletion in the thymus is concluded to be a critical process in immune aging and is found to be transiently protected from genetic instability by means of a feedback surveillance which functions at the expense of chronic thymic involution. In the immune control of mammalian aging, principles of Darwinian natural selection are suggested to work at the cellular level. During life, an immune-mediated stabilizing cell selection is displaced by a destabilizing one, thus changing physiological to pathological aging. In consequence, mammalian aging may be approached from an evolutionary point of view by both genetic cell variation and immune selection and be revealed correspondingly both as a stochastic and programmed process. Age-dependent diseases may be characterized as the consequence of localized pathological aging.