W. Spielmeyer[150] says that in the last decade the clinicians and pathological anatomists have discussed old age more than in preceding decades. We know that organs are used up and that their substance is not fully replaced. The functionally exciting parenchyma is injured by its own function and in this metabolism the quality and sometimes the volume of the organ is reduced. Thus old age is a function of the work of the organism and it seems to be an intrinsic quality of cells to use themselves up. Many do not regard age as a normal physiological process but with Metchnikoff think it is due to injurious substances, that is, endogenous toxins that are more important than the exogenous factors, so that blood vessels, glands, and muscle and ganglia cells degenerate. But the cortical cells, as the most sensitive of the organism, are more often injured. Metchnikoff thinks that the higher elements of the tissues are in conflict with the lower and are overcome by them, the phagocytes being left masters of the field. Few, however, hold this view. Ribbert, Naunyn, Hansemann, and Nothnagel think that outer and inner injuries should have precedence in accounting for old age. But without these coöperative factors there is a physiological determinant of the organism and its parts to be used up and they become senile and lapse by physiological processes, while Naunyn thinks that it is perhaps a general law that every organ fulfills its functional task only by impairment of its complete organic integrity. This using up of an organism by its own work occurs first in the brain and the central nervous system. There is a general decline in weight, even in the fourth or third decennium, which is accelerated in the seventies and may reach one hundred grams (Naunyn) and, in pathological states, still more. It is, therefore, of great interest for the relation of function and the use-up of organs that brain atrophy is not usually uniform or diffuse but that there is often a difference between the right and left hemispheres in the diminution of their volume. The left hemisphere is more used and usually more atrophied than the right. The left convolutions, therefore, suffer most reduction.