CHANGES IN HUMAN SKIN WITH AGING 831 at regular intervals and in increasingly larger doses (to compensate for the animals' increased tolerance). He was unable to note any effect on the life span of the animals. The evidence presented here would indicate, then, that there is no conclusive evidence of a causative link between stress and the phenomenon of biological senescence. SOMATIC MUTATION THEORY The next theory to be dealt with is that of somatic mutations. Its proponents feel that the changes in the aging organism are due to changes or mutations in the chromosomes, or genetic material, of the cell. The longer an organism lives, the more mutations it is liable to accumu- late (due to various causes) and the more inefficient the functioning of the cell will become, since it is assumed that practically all mutations are deleterious. After a time, the body cells will be functioning so inefficiently that either some internal metabolic disorder will result, or, because of an impaired immunologic defense system, the body will succumb to an invasion of some pathogenic agent. In the above explanation it has been implied that the genetic material of the cell exerts an influence over the cell's behavior long after the union of the gameres derived from the parental organisms. Indeed, within the past decade it has been shown that the function of the genes does not lie solely in determining hair and eye color, height, and other characteristics of the developing organism, but in the very intimate control which the genes exert over the biochemical machinery of the cell's metabolism. At this point, it would be instructive to make brief mention of this control as a background for the further explanation of the mutation theory. Gene Control It is known that the chromosomes which are present in the nuclei of all animal cells are composed of deoxyribonucleic acid or DNA. It is further believed that there are specific areas on the chromosome which are responsible for certain manifestations and activities in the organism these areas are called genes. It is under the direction of the basic chemical structure within the gene, the so- called genetic code, that the cellular proteins are manufactured and the most important group of proteins, perhaps, is the enzymes which catalyze most of the metabolic reactions in the living cell. Thus the genes of the organism exert direct control over the metabolic machinery of that organism by directing the synthesis of the major cellular cata- lysts.

832 JOURNAL OF THE SOCIETY OF COSMETIC CHEMISTS To relate this back to the mutation theory should not be too diffi- cult now. If a mutation caused by irradiation occurred, and a part of a chromosome were broken off, then the enzymes whose manufacture was involved with that portion of the chromosome would be affected. The practical problem, however, of how to detect possible mutations of this kind arises. Many of the somatic cells of the body do not usually form a second generation and so these chromosomal abnormal- ities would not be manifest in the daughter cells. Albert (4), however, has devised a technique of dosing mice with carbon tetrachloride and thus destroying about 60% of the normally nondividing liver cells. He reasoned that the ability of this organ to regenerate lost portions would then provide a method of recording chromosome abnormalities in second generation cells. Using this technique, Stevenson and Curtis (5) found a steady increase in chromosome aberrations as a function of increasing age the number of mutations reached a peak value of 22% of all the liver cells when the animals were 12 months old. The cells of the body which divide frequently, however, present quite a different situation than do the infrequently dividing cells. In the former types of cells, a mutation can arise much more easily and does not need radiation insult for its cause. In the process of replication of the nuclear DNA, if a wrong base lined up opposite its complementary half and were incorporated into the DNA, this would first cause mis- reading of the genetic code and then substitution of the wrong amino acid in the enzyme protein structure. In many cases, the substitution of one wrong amino acid in an enzyme leads to its inactivation, since much of an enzyme's activity depends upon its stereochemistry. While it is also true that in the frequently dividing body cells replication errors will tend to be eliminated by the process of natural selection, several faulty enzymes may be synthesized before this elimination takes place these enzymes will then be unavailable to mediate the reactions for which they were originally intended. Mutations, therefore, of both nondividing and dividing cells of the body play a very real role in the process of senescence, since they affect the fundamental control of cell function. CROSS-LINKAGE THEORY A third theory of aging concerns the possible cross linking of various of the body's most important molecules as it grows older. Bjorksten (6), one of the most vigorous proponents of this theory, has postulated