Aging is a deprivation syndrome driven by a germ-soma conflict.
Evolution through natural selection can be described as driven by a perpetual conflict of individuals competing for limited resources. Recently, I postulated that the shortage of resources godfathered the evolutionary achievements of the differentiation-apoptosis programming [Rev. Neurosci. 12 (2001) 217]. Unicellular deprivation-induced differentiation into germ cell-like spores can be regarded as the archaic reproduction events which were fueled by the remains of the fratricided cells of the apoptotic fruiting body. Evidence has been accumulated suggesting that conserved through the ages as the evolutionary legacy of the germ-soma conflict, the somatic loss of immortality during the ontogenetic segregation of primordial germ cells recapitulates the archaic fate of the fruiting body. In this heritage, somatic death is a germ cell-triggered event and has been established as evolutionary-fixed default state following asymmetric reproduction in a world of finite resources. Aging, on the other hand, is the stress resistance-dependent phenotype of the somatic resilience that counteracts the germ cell-inflicted death pathway. Thus, aging is a survival response and, in contrast to current beliefs, is antagonistically linked to death that is not imposed by group selection but enforced upon the soma by the selfish genes of the "enemy within". Environmental conditions shape the trade-off solutions as compromise between the conflicting germ-soma interests. Mechanistically, the neuroendocrine system, particularly those components that control energy balance, reproduction and stress responses, orchestrate these events. The reproductive phase is a self-limited process that moulds onset and progress of senescence with germ cell-dependent factors, e.g. gonadal hormones. These degenerate the regulatory pacemakers of the pineal-hypothalamic-pituitary network and its peripheral, e.g. thymic, gonadal and adrenal targets thereby eroding the trophic milieu. The ensuing cellular metabolic stress engenders adaptive adjustments of the glucose-fatty acid cycle, responses that are adequate and thus fitness-boosting under fuel shortage (e.g. during caloric restriction) but become detrimental under fuel abundance. In a Janus-faced capacity, the cellular stress response apparatus expresses both tolerogenic and mutagenic features of the social and asocial deprivation responses [Rev. Neurosci. 12 (2001) 217]. Mediated by the derangement of the energy-Ca(2+)-redox homeostatic triangle, a mosaic of dedifferentiation/apoptosis and mutagenic responses actuates the gradual exhaustion of functional reserves and eventually results in a multitude of aging-related diseases. This scenario reconciles programmed and stochastic features of aging and resolves the major inconsistencies of current theories by linking ultimate and proximate causes of aging. Reproduction, differentiation, apoptosis, stress response and metabolism are merged into a coherent regulatory network that stages aging as a naturally selected, germ cell-triggered and reproductive phase-modulated deprivation response.
Heininger
Kurt
K
Department of Neurology, Heinrich Heine Universität, Düsseldorf, Germany. kurt.heininger@web.de
D000375:Aging / Q000502:physiology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001481:Basal Metabolism / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D016922:Cellular Senescence / Q000502:physiology*; D005854:Germ Cells / Q000473:pathology / Q000502:physiology*; D006801:Humans; D013312:Stress, Physiological / Q000473:pathology / Q000503:physiopathology; D013577:Syndrome