Subject(s)
Leukemia, Radiation-Induced/etiology , Leukemia/etiology , Animals , Antibody Formation/radiation effects , Chromosome Aberrations , Female , Leukemia/veterinary , Male , Mice , Oncogenic Viruses/isolation & purification , Preleukemia/etiology , Preleukemia/veterinary , Rabbits , Radiation Genetics , Rodent Diseases/etiology , Swine , Swine Diseases/etiologyABSTRACT
Classic pathology tends to view old age as a composite of familiar, though not necessarily observable lesions. Modern gerontological research, in contrast, portrays chronic-progressive diseases that emerge from adulthood onward as mere complications of a universal condition called "aging." To integrate this view into both teaching and practice is the task faced by the pathologist interested in aging. The essay reviews current procedures used to estimate biological age (ie, to quantitate discrepancies between chronological and biological age), and the conceptual basis of these procedures. In addition, a new definition of aging is proposed: a time-dependent, irreversible shift from environmental to intrinsic causation of disease. This intrinsic pathogenesis has two components. The first is genetic and beyond the reach of contemporary health care. The second, more difficult to define, entails the growing number of degenerative lesions due to viral agents, as well as carcinogenesis. The conventional dichotomy between a malleable environment and an impregnable genome is blurred. Significant advances are more likely in the increasingly complex frontier area between them than within the genome itself.
Subject(s)
Aging , Aged , Geriatrics , HumansABSTRACT
One of the objectives of gerontological research is to achieve, reproducibly and at will, a verifiable discrepancy between the chronological and biological age of organisms. To accomplish this, the experimenter must be in a position to measure biological age independently. In theory, this can be done in the three ways: by actuarial analysis of large populations, assessment of overall morbidity, or observation of chronic degenerative changes that can be actually measured or graded according to a scale. Of these three approaches, only the last appears to be promising in experimental research. However, not all progressive degenerative changes represent practically useful parameters of biological age. Criteria for their evaluation are presented, and their theoretical prerequisites as well as concrete applications discussed. In a more general way, one has to be aware that biological age is a statistical entity. It cannot be directly observed but only inferred from quantifiable epiphenomena, and is, as such, not measurable like temperature or weight.
Subject(s)
Aging , Aged , Animals , Astrocytes/pathology , Basement Membrane/pathology , Brain/cytology , Cells, Cultured , Ceroid/metabolism , Chromosome Aberrations , Collagen/metabolism , Cricetinae , Environment , Genetic Diseases, Inborn/physiopathology , Geriatrics/methods , Hippocampus/pathology , Humans , Morbidity , Organ Size , Rats , Thymus Gland/anatomy & histology , Time FactorsABSTRACT
In the whole-body irradiated mouse, various late effects of radiation are observed after the recovery from acute radiation injury. Some of these account for the familiar proneness of certain mouse strains to develop leukemias. The two experiments described below were designed to (a) identify such preleukemic changes in blood-forming tissues and (b) to find ways to manipulate them experimentally with the purpose of preventing leukemia. Preleukemic change of the bone marrow appears to be a mere quantitative departure from normal in a qualitatively non-malignant tissue. It entails increased proneness of immature (precursor) cells to react with latent virus. Our data are consistent with the assumption that this proneness is enhanced (or brought about) by removal of a controlling influence exerted by the mature cells over their precursors (feed-back inhibition). Re-irradiation combined with intravenous bone marrow substitution offsets the leukemogenic influence of an earlier radiation exposure. The effect of re-irradiation on bone marrow displaying preleukemic lesions corroborates conclusions from earlier experiments on the nature of these lesions.
Subject(s)
Bone Marrow/pathology , Preleukemia/etiology , Radiation Chimera , Animals , Bone Marrow/radiation effects , Leukemia/mortality , Leukemia/prevention & control , Mice , Spleen/radiation effectsABSTRACT
In the x-irradiated mammal, the ratio erythrocytes/nucleated cells is positively correlated with the radiation dose. In the present report, this correlation is used to estimate, by means of marrow biopsies, the radiation dose received by whole-body exposed monkeys.
Subject(s)
Bone Marrow Cells , Bone Marrow/radiation effects , Radiation Injuries, Experimental/pathology , Animals , Biopsy , Bone Marrow/pathology , Bone Marrow Examination , Cell Count , Erythrocyte Count , Female , Haplorhini , Male , Radiation Dosage , X-RaysABSTRACT
Radiation which induces leukemogenesis in the unirradiated mouse, inhibits leukemogenesis if given again to the previously irradiated, but not yet leukemic mouse. The objective of this experiment was to identiry nonmalignant late radiation in jury in the bone marrow, the modification of which by a second exposure may account for postponement of radiogenic leukemia. To this end, leukemogenically irradiated RFM/Up mice were reirradiated under conditions known to bring about postponement of the leukemias due to the first radiation exposure. Quantitative analysis of the femoral pone marrow of these mice shows that leukemia incidence is positively correlated with the number of immature myeloid cells, and negatively correlated with the percentage of the mature myeloid cells in the entire myeloid series. The implications of this for the understanding of preleukemic change are discussed.
