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differentiation products continues long enough it necessarily leads to the death of the cell, since the continued life of the cell depends upon the interaction between the general protoplasm and the nucleus. In cells laden with the products of differentiation, the power of regulation is first lost, then the power of division, and finally the power of assimilation; and this is normally followed by the senescence and death of the cells.

In some cases the progressive transformation of protoplasm into metaplasm may be reversed; in some manner the formed material is dissolved and converted into general protoplasm, the protoplasm and nuclei increase in size, the cells begin to divide and may become capable of regulation. In short, this reversal of the differentiation process leads to the rejuvenescence of senile cells. Minot holds that differentiated cells do not become undifferentiated—but at least it must be admitted they may lose their products of differentiation and metabolism; gland cells lose their secretion granules, egg cells their yolk, spermatozoa within the egg their flagella, injured muscle cells their fibrillge, etc. In such cases differentiation products are either eliminated from the cell or are transformed into a more labile and more general form of protoplasm, though the latter is probably not undifferentiated. I have used the term dedifferentiation for this process.

Among functional causes of senescence may be mentioned the well-known opinion of Metschnikoff, that the organism is slowly poisoned by its own waste products. Metschnikoff especially emphasizes the effects of intestinal fermentation and putrefaction in producing old age. Zoologists are familiar with the fact that, in certain Polyzoa and Tunicata which lack kidneys or efficient means of eliminating urea, or other nitrogenous waste, the tissues gradually become laden with such waste substances and the animal becomes senile and finally dies, but before this happens it may give off one or more buds which are relatively free from these waste products and which continue the life of the colony. It is a general phenomenon both in plants and animals that buds are composed of protoplasm which is not laden with products of differentiation or metabolism, and hence they exhibit youthful characteristics although the body from which they come may be senile.

Another functional cause of senescence is to be found in a decrease in the power of constructive metabolism. This factor has been recently advocated by Child in a very valuable paper, in which he concludes that anything which decreases the rate of metabolism, such as "decrease in permeability, increase in density, accumulation of relatively inactive substances, etc.," will lead to senescence. On the other hand, "Rejuvenescence consists physiologically in an increase in the rate of