Senescence, the Last Half of Life

by G. Stanley Hall

As to checking the advance of old age in women, Steinach is not yet ready to make any positive report, but in view of what has already been done with animals he thinks a good prognosis can be made and that the best method is by implantation of young ovarian material. The difficulty of this orthoplastic process is found only in the dependence upon the material of implantation, which is very difficult to secure. The effort is directed in all such cases to the influence of the aging ovaries, whether operative by orthoplastic transplantation or by the use of Roentgen rays. The former, on account of the earlier involution of ovaries, is confined within certain limits to women. The phenomena of fatigue, etc., have been removed by this method, which has been so successful that improvement has been noticed by friends.

In Steinach’s experiments with rats, which pass through the life stages so rapidly, he used the method of transplantation of testicular glands furnished by three-months-old individuals and this grafting need not necessarily be in situ but in various parts of the body. If intussusception took place, as it generally did if the operation was well performed, the change here was generally marked within two weeks, as his photographs show. More or less of Steinach’s work has been confirmed, Ebstein tells us, by other observers who have shown that not only in rats but in guinea pigs the transfer of ovaries and testes between the sexes makes the male, to some extent, become female, and vice versa. Sex differences, Steinach thinks, do not result from anatomical differences in the organs transferred but are due to functions residing in certain cells, especially those of Leydig or Lutein. It is their secretions that determine sex characteristics. Indeed, they are really glands and vitality and vigor depend upon their state. Youth is the freshening up of these glands. No one has recognized more clearly than Steinach that there is a false old age that has been, in a sense, imposed by civilization upon elderly people and given them a rôle they have more or less passively accepted, just as in the same way there are spurious forms of other diseases. Some of Steinach’s critics have suggested that all he has done is to throw off these artificial inhibitions and give old age the true character nature intended it to have. But even if this criticism has any weight against his conclusions respecting old age in man, it certainly cannot apply to his studies of senescent animals, for in them the traits of old age were unmistakable, as not only photographs but, far more, activities showed. They certainly do seem to be really rejuvenated and not merely to be laying aside a sham old age.

Of the half-dozen or more expert opinions upon Steinach’s work nearly all have been by his own countrymen and by far the most exhaustive and, on the whole, highly favorable is that of Paul Kammerer.[185] For a very condensed account of it in English see A. Granet’s résumé[186] in which he says (1) that Steinach’s work is based on a new conception of the puberty gland as the internal secretory portion of the gonads. This consists of the interstitial cells in the male and of the lutein cells in the female. (2) Steinach began by studying animals with a protracted rutting period in alternating stages of development of the interstitial gland and the generative gland proper. He found a periodical hyperdevelopment in the evolution of every individual, the interstitial gland predominating in infancy and attaining its maximum development at puberty and adolescence, when growth and vital energy are also at their maximum. At this time the generative gland increases and both the interstitial and generative portions continue to be about equally active till the climacteric, after which there is rapid recession of the interstitial gland, and this causes senility, which is not due to the ultimate using up of all elements but to the lack of potential stimulus due to degeneration of the interstitial gland. (3) Steinach used this alternating balance of nature in the mixed gland by artificially inhibiting the generative portion and thereby causing compensatory regulation and revival of the interstitial portion with all its rejuvenating effects and the recession of the traits of senility. This he accomplished by three methods (a) simple ligation, under local anæsthesia, of the vas deferens. This causes regression of the generative gland and a compensatory regeneration of the interstitial portions. A one-sided operation is sufficient in all cases and has the advantage of preserving in addition the power of procreation. Of course ligation of the Fallopian tube in the female does not produce this result. (b) Repeated mild exposure of the gonads to the X-ray is a slower but apparently just as effective a means of obtaining the same result for both ovaries and testes. And lastly, (c) the effects of rejuvenation may be experimentally produced by transplantation in the old of the respective gonads of the young animal of the same species. For years Steinach bred and reared healthy generations of laboratory animals and studied their dispositions, habits, physical and psychic traits, until he has become unprecedentedly expert in diagnosing age, to say nothing of sex. The increased resistance to disease and the actual prolongation of life of the operated animals he estimates at about 25 per cent but after a time senescence sets in again.

For women in the climacteric the X-ray method is, by general consent, best. But Steinach contends that increased well-being and capacity thus caused are really due to regeneration of the interstitial ovarian structures. General debility and climacteric metrorrhagias are distinctly helped by this method because the interstitial portion of the ovary is not affected by the X-ray whereas the colloidal-albuminoid precipitation occurs in the cells of the Graafian follicles, which are radio-sensitive, the same as the metaplastic cells. The affected cells disappear by autolysis. Menopause sets in and the interstitial portion alone whose hormones produce the rejuvenating effect remains functioning. The effects of transplantation, too, are the same and the shrinking of the transplanted gland seems due to atrophy and should not prevent rejuvenating effects.

E. Payr[187] calls attention to the fact that Steinach’s puberty glands, which correspond to the Leydig cells, are those that secrete internally and that it is these that act so powerfully upon secondary sex qualities and bring what often appears to be a renewal of youth. His operation is especially indicated in the case of subjects with healthy internal organs who are growing prematurely old and who give evidence of loss of function of secondary sexual characteristics.

G. F. Lydston[188] describes nine cases of men with atrophied testes, injured, or removed, which were replaced in situ surgically by those from the bodies of boys recently dead. The glands from the boys were removed within a few hours after death and generally subjected to cold storage for some hours and then ingrafted upon the older patient. The boys from whom they were taken were healthy boys who had suffered sudden or violent death and there might be an interval of many hours not only between the death and the removal but between the latter and the implantation. In all these cases Lydston reports more or less improvement by the operation, which in a few cases was marked. The transplanted glands atrophy and disappear more rapidly when the recipient has more or less well developed testes of his own. Apparently permanent local results were best obtained in those cases in which the patient had very little gland tissue. Lydston thinks that there may be a sort of parasitic action of the patient’s own glands upon the transplanted ones. His own organs probably contribute the nutritive pabulum otherwise available for the implanted ones but the therapeutic results are obtained and sustained even when the implanted gland eventually disappears. He thinks that the notable result obtained by Dr. I. L. Stanley, where the glands from a Negro hanged for murder were implanted in the scrotum of a white moron, apparently with remarkable results, suggests that atrophy may take place more slowly when the donor is of the same race as the recipient. The author doubts whether there is much advantage in anastomosis as to either betterment of nutrition or preservation of the spermogenetic function. He thinks “we run more risk of failure of the implant from the greater traumatization of the tissue necessary for anastomosis.” He thinks, too, that the spermogenetic epithelium of the testes degenerates in all cases rather promptly.[189]

In his book, Impotence, Sterility and Sex Gland Implantation (1917), which seems somewhat ill-digested, Lydston claims priority on eight points and formulates twenty-one conclusions. It seems to me that he has not sufficiently assimilated the best European work in this field or profited as much as he might have done by the far greater refinements of technique of Steinach; while such results as he claims are, as he himself admits, always wide open to criticism.

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Serge Voronoff, like Metchnikoff, combines research with humanism and gives free rein to his idealism. He is professor in the medical school of the Collège de France and deals with old age and death from the standpoint of endocrinology or the study of the glands of internal secretion. Accepting Weismann’s doctrine of the continuity of germ plasm, he says that the nameless and ever unassuaged horror that everybody really feels for death is “because an intimate memory of our immortality” survives or because we recollect creation’s first intention as expressed in plasmal immortality. Man has inherited this longing from the deathless unicellular creatures from which he descended not only in the form of quests for elixirs of life here but in all his manifold beliefs of a life beyond the grave, at the same time for this life accepting the gospel of renunciation to death as something inevitable. The ghastly thought of death not only clouds all our life but predisposes even most scientists to think that research in this field cannot be successful.

The background view of the work in Voronoff’s field, roughly stated, is as follows. Somatic cells, having lost the power to propagate the whole body, as they develop and multiply become more and more special, not only in form but in function, until they finally lose the power of multiplication or of regeneration. These are higher and perform the most particularized functions. Besides these most individualized cells, so characteristic of every organ that a cytologist can at once distinguish cells that form the epithelium, intestines, brain, muscle, glands, etc., there always remain other far less differentiated or more primitive cells, chiefly leucocytes or white blood corpuscles and the connective tissue cells. The former float in the blood and can pass out through the thin walls of the capillaries into other tissues. The latter constitute all the firmer supportive framework of every organ. They are very robust, fecund proletarians and are largely made up of the former. From birth they wage unceasing war upon the nobler, more professional and expert, but less independent cells which have sacrificed most of their cruder, pristine powers for service to the body corporate. These higher cells represent the extreme division of labor within our bodies. They are no longer sufficient unto themselves but each class of them depends upon the work of others. The low, banal, barbaric but vigorous cells of the conjunctive tissue, on the other hand, always strive to destroy and to themselves take the place of the higher cells and it is this process slowly going on everywhere that constitutes old age and all its processes of hardening, atrophy, disintegration, etc., for these lower cells cannot discharge the functions of the higher ones they have supplanted and hence comes anarchy within the organ or body. We die because nature tends so strongly to develop the cruder type of cell that makes up the connective tissue.