The symptoms of senescence are evidently the expression of profound physicochemical changes which occur in the humors and the tissues of the organism under the influence of time. But the nature of these changes is still utterly unknown. If the modifications of blood serum and interstitial lymph which are functions of the age of the organism could be quantitatively studied, it is probable that the mechanism of growth, differentiation, and senescence would be better understood. Some years ago, one of the writers attempted to develop a method, for detecting these modifications. By cultivating connective tissue in the plasma of chickens of different ages he found that the growth was more abundant in the plasma of the younger than in that of the older animals.: This fact suggested that proliferating fibroblasts could be used as a reagent for the changes occurring in the blood under the influence of age, if a technique sufficiently accurate were developed. During the last few years, the necessary improvements in the methods of cultivating tissues have been realized. ",8 It has, then, become possible to study the cause of the slower multiplication of fibroblasts in the serum of old animals and the factors of senescence. The experiments of Loeb and Northrop on the temperature coefficient of duration of life of Drosophila lead to the conclusion that the duration of life was probably determined by the production of a substance leading to old age, or by the destruction of a substance which normally prevents old age and natural death. ~ It was important to know which of these
1. Monocytes and tissue macrophages become identical in appearance when they live under identical conditions. Macrophages cultivated in nutrient and non-nutrient media acquire different structures. Monocytes and tissue macrophages are mere functional variations of a single type. 2. The structure of the segregation apparatus and of the mitochondria of monocytes and macrophages depends on the composition of the pericellular fluid and on the metabolic state of the cells. 3. The monocyte and the macrophage are endowed with a number of physiological properties which become apparent when they grow in pure cultures. 4. The knowledge of these fundamental characteristics explains the behavior of the cells within the organism.
In normal cultures, the transformation of monocytes into fibroblasts generally occurred when cells became packed together through some mechanical factors that prevented their free migration and determined their accumulation. Various modifications of the medium, the addition of dead tissue, and of trypsin or the products of trypsin digestion, failed to bring about the transformation. The inoculation af cultures of monocytes with filtered extract of Rous sarcoma frequently determined the appearance of fibroblasts. The first change undergone by the monocytes cultivated in vitro was a large increase in their size. Later, the giant monocytes became transformed into cells that did not differ essentially from those that grow from a fragment of adult connective tissue.
It may be concluded that, under the conditions of the experiments: 1. The inhibiting action on homologous fibroblasts of the heated serum of a young animal increases relatively more than that of an old animal. After it has been heated, the inhibiting action of the serum of the old animal is still greater than that of the young animal. 2. The CO2 precipitate obtained from the serum of a young animal definitely increases the proliferative activity of homologous fibroblasts, while the CO2 precipitate of the serum of an old animal has practically no activating power. After the removal of the CO2 precipitate, the inhibiting action of the serum of young animals is increased, while that of old animals is not modified. 3. The increased inhibiting action of serum on homologous fibroblasts in old age is partly due to the disappearance of the growth-activating substances and to the enhanced activity of the growth-inhibiting principle.
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