The possibility must be borne in mind that the use of thyroid and other gland extracts that have a definite effect on metabolism is not devoid of risk to cells that are gradually undergoing involution; for, by stimulating metabolism unduly, the existing vitality may be prematurely exhausted and, though for a time there is a gratifying show of energy, it is but a flash in the pan that precedes a more rapid loss of function. We are irresistibly reminded that “no man putteth new wine into old bottles: else the new wine doth burst the bottles.”
At the present time it would be unwise to express a dogmatic opinion about the relation of the endocrine glands to normal old age. That old age is due to endocrine insufficiency or loss of balance cannot be regarded as proved, and it is probably safer to regard changes, such as atrophy, in the various glands of internal secretion as concomitant with, rather than causal of, those in the senescent body.
Metchnikoff’s Pathological Explanation
As an alternative to the belief that there is an inherent quantum of vitality which may be harmfully or beneficially influenced by environment and the wear and tear of life, it has been suggested that the process of ageing depends solely on external factors and that either there is no intrinsic limitation to the life of the organism or that the possibility is entirely cast into the shade by predominance of extrinsic influences. This doctrine is free from any tinge of fatalism and has the advantage that it is a direct stimulus to efforts in the direction of hygiene in all its forms; for as things are now old age owes its discomforts to superadded and in most instances avoidable complications. Élie Metchnikoff, as is well known, attributed the senile accompaniments of advanced years to pathological and preventible causes, namely toxaemia induced by alcohol, syphilis, and especially by bacterial activity in the colon which in common with Barclay-Smith and Arbuthnot Lane, he regarded as a harmful phylogenetic relic, this point of view being expressed by the epigram “the longer the colon the shorter is life.” He considered that the putrefactive bacteria in the colon produce phenol, indol, skatol, and aromatic bodies which cause degenerative changes in the cells of the body; and that the more resistant macrophages, which do not attack healthy tissues, absorb the damaged cells. He therefore employed means to prevent excessive bacterial activity in the large intestine, and in addition to care in diet so as to diminish the risk of introducing bacteria into the alimentary canal, he advocated the destruction of putrefactive bacteria in the colon by means of sour milk and cultures of Bacillus bulgaricus, which form lactic acid and thus render the contents of the bowel acid and unsuitable for the growth of the harmful micro-organisms. Metchnikoff thoroughly practised his doctrine, but he did not begin his regime until he was well over fifty, and, in spite of several severe illnesses which had damaged his heart, he lived longer than any of his family and passed the 70th milestone. His views on the method of production of senility aroused great interest and criticism not only from Marinesco,[122] Léri,[123] Sand, Laignel-Lavestine, and Voisin, who disputed the reality of the macrophages devouring the cells of the central nervous system, and Ribbert[124] who denied the existence of such a physiological intoxication and ascribed old age and death to the inevitable physico-chemical changes incident to life, but also from Salimbeni and Gery,[125] working in the Pasteur Institute, who while supporting most of his contentions did not consider that they provided the whole explanation, e.g., the involution of the ovaries at a fixed age was not thus accounted for. The means Metchnikoff advised for the postponement of senility and death were on much broader lines than the popular conception summed up by “sour milk” might suggest, for he expounded the philosophy of orthobiosis or a correct method of living.
That intestinal toxaemia due to stasis has a very important influence in producing disease cannot be doubted, and Sir Arbuthnot Lane[126] has brought this prominently to our notice; while clothing in modern language the old ideas of the primae viae he recalls to our memory Abernethy’s[127] panacea for many ills of the flesh, namely a blue pill at night followed by a mixture of gentian and senna in the morning.
Among his collaborators Mr. Ernest Clarke[128] has insisted on the premature ageing of persons with intestinal stasis. From the analogy of syphilis, alcoholism, and other intoxications, which may produce degenerative changes simulating those found in old age, the hypothesis of intestinal toxaemia gains a certain amount of support, and it may not be so easy to exclude the agency of intestinal toxaemia as in the case of syphilis and some intoxications. But intestinal toxaemia may, as far as can be judged, be absent in healthy old age, and conversely be present in early life without causing the phenomena of old age. Further objections have been raised:—why should intestinal toxins be harmless for 40 or 50 years and then exert such a serious influence? why should women who are more subject than men to constipation be more long-lived; and that in constipated persons the faeces, as shown by Schmidt and Strasburger, contain fewer living bacteria than in health.[129]
As applied to normal old age and death this hypothesis is pathological and therefore has rather failed to interest those who are working at the biological aspect. Perhaps the most that can be safely concluded in balancing the pathological and biological arguments is that while Metchnikoff’s view may be partially true it does not account for all senile changes, and that normal old age or senescence cannot be regarded as the result of toxins absorbed from the alimentary canal.
Old Age of Cells and Carcinoma
The relation between ageing of the cells on the one hand and the development of carcinoma on the other hand is a subject of great interest. According to Karl Pearson’s[130] statistical enquiry the incidence of carcinoma reaches its maximum at the age of 46 years in women and 56 years in men; Lazarus-Barlow[131] concluded that the range of years over which cancer is likely to occur is practically the same in the two sexes, namely 46 to 64, and that among 4659 cases of malignant disease there were only 35, or 0·7 per cent, over 80 years of age.[132] The cancer age, therefore, coincides with the waning of maturity and the onset of old age; that carcinoma is rare in very old persons is also shown by the occurrence of one case only among 71 centenarians collected by Sir George Humphry. Laurent[133] considered that whereas longevity depends on a condition of vital equilibrium, the development of cancer is due to a want of this equilibrium, to a state of anarchy, and that the factors disposing to orderly vitality are conducive to longevity and antagonistic to the development of new growth. The reason why malignant growths are prone to appear with the onset of old age has naturally been the subject of much debate. According to Thiersch degeneration lessens the controlling influence normally exerted by connective tissue on epithelium, the inherent proliferative capacity of which then runs riot. Ribbert believed that from loss of resistance or diminution of surface tension in the connective tissues post-natal “rests” of epithelium were produced as the result of irritation and that these displaced cells then grew because there was no controlling opposition. Adami suggested a reversion of the highly specialized epithelial cells to a simpler form with powers of proliferation, the cumulative habit of growth taking the place of the habit of work, and practically anticipated the more modern view. According to Hastings Gilford[134] malignant disease is a premature cell senility and the result of the partial reversion of immature or adult cells to an embryonic or quasi-embryonic state. From a study of senescence in dogs Goodpasture[135] concludes that degenerative changes in the cells lead not only to death of some cells but to dedifferentiation of others, which, becoming simpler in structure and function, recover their juvenile power of growth in varying degrees, and that hence metaplasia and tumour growths occur as accidents of commencing old age. A little later Oertel[136] insisted on his view that cancer is not an embryonic reversion or a specific change in the cell but a phenomenon of senescence—a degenerative proliferation depending upon disturbances in the nucleus plasma relations, specifically upon the loss of nuclear chromosomes; from age or degeneration the tumour cell loses the higher functional chromosomes and retains the genetically older and more resistant ones controlling reproduction and vegetative activities; thus there arises a race of cells without the differentiation of undegenerated cells.
These various expressions of opinion would justify the conclusion that with the onset of old age the degenerative processes in the cells lead to the production of less specialized cells which have the compensating property of more vigorous growth, and that in certain circumstances, one of which is very probably a diminished power of resistance on the part of the surrounding tissues and another, and very important one, irritation in some form or another, riotous proliferation of the cells invades the adjacent parts. That the conditions necessary are usually local is strongly suggested by the appearance of the new growth at one spot only and by the frequent absence of recurrence after free removal. There may be a premature local senescence of the tissues, just as there is premature old age of the body generally, and this would explain the exceptional occurrence of malignant disease in early life or long before the usual time.