Similar conditions of renewed vigor are shown by many animals after long hibernation. The great breeding activity of many animals, such as frogs, so soon after their winter sleep, may find a physiological explanation in this using up of metabolic products during hibernation and the subsequent increase in vitality.
In similar manner it is known that the new tissue which is formed in regeneration comes from undifferentiated (epithelial or lymphoid) or from dedifferentiated cells (e. g., muscle cells of amphibia, etc.). In the latter case also there is a rejuvenescence, due to the loss of differentiation products. In this case dedifferentiation is evidently due, in the first instance, to the injury. It is at least possible that the failure to regenerate lost parts, which many animals show, is due to the inability of the cells to undergo dedifferentiation and subsequent rejuvenation.
In conclusion, we find that the life of a cell is dependent upon the continued interaction of nucleus and protoplasm; that as the protoplasm is transformed into products of differentiation this interaction of nucleus and protoplasm is reduced and constructive metabolism is diminished; that when the quantity of protoplasm present has been reduced beyond a certain point, either by its transformation into metaplasm, or by other means, constructive processes fail to compensate for destructive ones, and the cell grows old and finally dies. On the other hand, processes which lead to the increase of the general protoplasm in a cell, either by the growth of the protoplasm already present or by the conversion of metaplasm into protoplasm, lead also to the growth of the nucleus, to increased interchange between nucleus and protoplasm, and hence to increased powers of assimilation, cell division and regulation. Anything which decreases the interchange between nucleus and protoplasm leads to senility; anything which decreases this interchange renews youth.
