PART I

THE INVESTIGATION OF OLD AGE

I

THE PROBLEMS OF SENILITY

Treatment of old people in uncivilised countries—Assassination of old people in civilised countries—Suicide of old people—Public assistance in old age—Centenarians—Mme. Robineau, a lady of 106 years of age—Principal characters of old age—Examples of old mammals—Old birds and tortoises—Hypothesis of senile degeneration in the lower animals

In the “Nature of Man” I laid down the outlines of a theory of the actual changes which take place during the senescence of our body. These ideas, on the one hand, have raised certain difficulties, and, on the other, have led to new investigations. As the study of old age is of great theoretical importance, and naturally is of practical value, I think that it is useful to pursue the subject still further.

Although there exist races which solve the difficulty of old age by the simple means of destroying aged people, the problem in civilised countries is complicated by our more refined feelings and by considerations of a general nature.

In the Melanesian Islands, old people who have become incapable of doing useful work are buried alive.

In times of famine, the natives of Tierra del Fuego kill and eat the old women before they touch their dogs. When they were asked why they did this, they said that dogs could catch seals, whilst old women could not do so.

Civilised races do not act like the Fuegians or other savages; they neither kill nor eat the aged, but none the less life in old age often becomes very sad. As they are incapable of performing any useful function in the family or in the village, the old people are regarded as a heavy burden. Although they cannot be got rid of, their death is awaited with eagerness, and is never thought to come soon enough. The Italians say that old women have seven lives. According to a Bergamask tradition, old women have seven souls, and after that an eighth soul, quite a little one, and after that again half a soul; whilst the Lithuanians complain that the life of an old woman is so tough that it cannot be crushed even in a mill. We may take it as an echo of such popular ideas that murders of old people are extremely common even in the most civilised European countries. I have been astonished in looking through criminal records to see how many cases there are of the murder of old people, specially of old women. It is easy to divine the motives of these acts. A convict of the Island of Saghalien, condemned for the assassination of several old persons, declared naïvely to the prison doctor: “Why pity them? They were already old, and would have died in any case in a few years.”

In the celebrated novel of Dostoiewsky, “Crime and Punishment,” there is a tavern scene where young people discuss all sorts of general topics. In the middle of the conversation a student declares that he would “murder and rob any cursed old woman without the least remorse.” “If the truth were told,” he goes on to say, “this is how I look at the thing. On the one hand a stupid old woman, childish, worthless, ill-tempered, and in bad health; no one would miss her, indeed she is a nuisance to everyone. She does not even herself know any reason why she should live, and perhaps to-morrow death will make a good riddance of her. On the other hand, there are fresh and vigorous young people who are dying in their thousands, in the most senseless way, no one troubling about them, and everywhere the same thing is going on.”

Old people not only run the risk of murder; they very often end their own lives prematurely by suicide.

They prefer death to a life oppressed by material hardships or burdened by diseases. The daily papers give many instances of old people who, tired of suffering, asphyxiate themselves by their charcoal stoves.

The frequency of suicide in the case of the old has been established by numerous statistics, and the new facts which I now cite do no more than confirm it. In 1878, in Prussia, amongst 100,000 individuals there were 154 cases of suicide of men between the ages of 20 and 50, but 295, that is to say, nearly twice as many of men between the ages of 50 and 80. In Denmark, a country in which suicide is notoriously common, a similar proportion exists. Thus, in Copenhagen, in the ten years from 1886 to 1895, there were 394 suicides of men between 50 and 70. These figures relate to 100,000 individuals. Of the suicides 36-1/2 per cent. were those of people in the prime of life, 63-1/2 per cent. those of the aged.[1]

In such circumstances, it is natural that politicians and philanthropists have made many attempts to ameliorate the old age of the poor. In some countries laws have been passed to bring about this. For instance, a Danish law of June 27th, 1891, established compulsory aid for the aged, enacting that every person more than 60 years old was to have the legal right to aid if required. In 1896 more than 36,000 people (36,246) were pensioned under this law, at a cost of nearly £200,000. In Belgium, the indigent old people are not pensioned until they reach the age of 65. In France, until recently, the aged poor could be supported at the public expense only by prosecuting them and sending them to prison for begging. This state of affairs, however, ceased with the application of the law of July 15th, 1905, according to which any French subject without resources, unable to support himself by work, and either more than 70 years of age, or suffering from some incurable infirmity or disease, is to receive public assistance.

It has been thought the proper course to make such laws, and to lay the burden on the general population, without inquiring if it may not be possible to retard the debility of old age to such an extent that very old people might still be able to earn their livelihood by work. Old age can be studied by the methods of exact science, and there may yet be established some regimen by which health and vigour will be preserved beyond the age where now it is generally necessary to resort to public charity. With this object, a systematic investigation of senescence should be made in institutions for the aged, where there are always a large number of people from 75 to 90 years old, although centenarians are extremely rare. I know many institutions for aged men where, from their first foundation, there has been no case of an inhabitant reaching the age of 100, and even in similar institutions for women, although women live to much greater ages than men, centenarians are very rare. At the Salpêtrière, for instance, where there is always a large number of old women, it is the rarest chance to find a centenarian. Opportunity for the study of the extremely aged is to be found only in private families.

Most of the centenarians whom I have been able to see have been so defective mentally that all that can be studied in them are the physical qualities and functions. A few years ago an old woman who had reached her 100th year was the pride of the Salpêtrière. She was bedridden and extremely feeble physically and mentally. She replied briefly when she was asked questions, but apparently without any idea of what they meant.

Not long ago, a lady who lived in a suburb of Rouen reached her 100th birthday. The local newspapers wrote exaggerated articles about her, praising the integrity of her mind and her physical strength. I paid a visit to her myself, hoping to make a detailed investigation, but I found at once that the journalists had completely misrepresented her condition. Although her physical health was fairly good, her intelligence had degenerated to such an extent that I had to abandon the idea of any serious investigation.

The most interesting of all the centenarians with whom I have become acquainted had reached an extremely advanced age, having entered upon her 107th year. It is about two years ago that a journalist, Monsieur Flamans, took me to see this Mme. Robineau who lived in a suburb of Paris. I found her a very old-looking lady, rather short, thin, with a bent back, and leaning heavily on a cane when she walked. The physical condition (Mme. Robineau was born on January 12th, 1800), of this woman of more than 106 years, showed extreme decay. She had only one tooth; she had to sit down after every few steps, but, once comfortably seated, she could remain in that position for quite a long time. She went to bed early and got up very late. Her features displayed very great age (see Fig. 1), although her skin was not extremely wrinkled.

The skin of her hands had become so transparent that one could see the bones, the blood-vessels, and the tendons. Her senses were very feeble; she could see only with one eye; taste and smell were extremely rudimentary; her hearing was her best means of relation with the external world. None the less, Dr. Löwenberg, a well-known aurist, had assured himself that her auditory organs showed in a most marked degree, the usual signs of old age, such as complete insensibility to high notes and slight deafness for low notes. Dr. Löwenberg attributed these changes to senile degeneration of the ear which affected more and more seriously the nervous mechanism although it had caused little change in the conducting apparatus. Notwithstanding her physical weakness, Mme. Robineau retained her intelligence fully, her mind remained delicate and refined and the goodness of her heart was touching. In contrast with the usual selfishness of old people, Mme. Robineau took a vivid interest in those around her. Her conversation was intelligent, connected, and logical. Examination of the physical functions of this old lady revealed facts of great interest. Dr. Ambard found that the sounds of the heart were normal, but perhaps a little accentuated. The pulse was regular, 70 to 84 a minute, and its tension was normal. The arterial pressure was 17. The lungs were sound. All these facts testify to her general health. The most remarkable circumstance was the absence of sclerosis of the arteries, although such degeneration is usually believed to be a normal character of old age.

Analysis of the urine, made on several occasions, showed that the kidneys were affected with a chronic disease, which, however, was not serious.[2]

Although the sense of taste was weak, Madame Robineau had a fair appetite. She ate and drank little, but her diet was varied. She took butcher’s meat or chicken extremely seldom, but ate eggs, fish, farinaceous food, vegetables, and stewed fruit, and drank sweetened water with a little white wine, and sometimes, after a meal, a small glass of dessert wine. The processes of alimentary digestion and excretion were normal.

It has sometimes been thought that duration of life is a hereditary property. There was no evidence for this in the present case. Madame Robineau’s relatives had died comparatively early in life, and a centenarian was unknown in her family. Her great age was an acquired character. Her whole life had been extremely regular. She had married a timber merchant, and had lived for many years in a suburb of Paris in comfortable circumstances. Her character was gentle and affectionate; she was thoroughly domesticated, and had been devoted to home life with very few distractions.

At the age of 106 years, her intelligence suddenly became weak. She lost her memory almost completely, and sometimes wandered. But her gentle and affectionate disposition remained unaltered.

The appearance of aged persons is too well known to make detailed description necessary. The skin of the face is dry and wrinkled and generally pale; the hairs on the head and the body are white; the back is bent, and the gait is slow and laborious, whilst the memory is weak. Such are the most familiar traits of old age. Baldness is not a special character; it often begins during youth and naturally is progressive, but if it has not already appeared, it does not come on with old age.

The stature diminishes in old age. As the result of a series of observations, it has been established that a man loses more than an inch (3·166 cm.), and a woman more than an inch and a half (4·3 cm.), between the ages of fifty and eighty-five years. In extreme cases, the loss may be nearly three inches. The weight also becomes less. According to Quételet, males attain their maximum weights at the age of forty, females at that of fifty. From the age of sixty years onwards, the body becomes lighter, the loss at eighty being as much as thirteen pounds.

Such losses of height and weight are signs of the general atrophy of the aged organism. Not merely the soft parts, such as the muscles and viscera, but even the bones lose weight, in the latter case the loss being of the mineral constituents. This process of decalcification makes the skeleton brittle, and is sometimes the cause of fatal accidents.

The loss of muscular tissue is specially great. The volume diminishes, and the substance becomes paler; the fat between the fibres is absorbed, and may disappear completely. Movements are slower, and the muscular force is abated. This progressive degeneration has been examined by dynamometrical measurements of the hand and the trunk, and is greater in males than in females.

The volumes and weights of the visceral organs similarly become smaller, but the diminution is not uniform.

The old age of lower mammals presents characters similar to those found in man. I can now give other instances than the case of the old dog which I described in the “Nature of Man.”

I will first take the case of old elephants, described by a competent observer. “The general appearance is wretched, the skull being often hardly covered with skin; there are deep abrasions under the eyes, and smaller ones on the cheeks, whilst the skin of the forehead is very often deeply fissured or covered with lumps. The eyes are usually dim, and discharge an abnormal quantity of water. The margin of the ears, specially on the lower side, is usually frayed. The skin of the trunk is roughened, hard, and warty, so that the organ has lost much of its flexibility. The skin on the body generally is worn and wrinkled; the legs are thinner than in maturity, the huge mass of muscles being much shrunken, whilst the circumference, especially just above the feet, is considerably reduced. The skin round the toe-nails is roughened and frayed. The tail is scaly and hard, and the tip is often hairless.

Horses begin to grow old much sooner than elephants. I reproduce (Fig. 2) the photograph of a rare instance of longevity, a mare 37 years old, which belonged to M. Métaine, in the department of Mayenne. The skin, bare in places, but elsewhere covered with long hairs, shows considerable atrophy. The general attitude reveals the feebleness of the whole body. Many birds, on the other hand, show at similar ages very slight external change, as may be seen from the photograph of a duck more than 25 years old (Fig. 3) which belonged to Dr. Jean Charcot. At a still greater age, as may be seen occasionally in parrots, the general debility of the body reveals itself in the attitude, in the condition of the feathers, and in the swelling of the joints. On the other hand, the oldest reptiles which have been observed do not differ in appearance from normal adults of the same species. I have in my possession a male tortoise (_Testudo mauritanica_) given me by my friends MM. Rabaud and Caullery, and which is at least 86 years old. It shows no sign of old age, and in all respects behaves like any other individual of this species. More than 31 years ago it was wounded by a blow, the traces of which remain visible on the right side of the carapace (Fig. 4). In the last three years the tortoise lived in a garden at Montauban, along with two females which laid fertile eggs. The old male, although, as I have said, probably at least 86 years of age, was still sexually healthy.

I have borrowed from the interesting volume of Prof. Sir E. Ray Lankester[3] the figure (Fig. 5) and description of a giant tortoise from the island of Mauritius, which is probably the oldest of all living animals. It was brought to Mauritius from the Seychelles in 1764, and has lived since then in the garden of the Governor, and as it has thus already been 140 years in captivity, its age must be at least 150 years, although we have not exact information. Notwithstanding this, it shows no signs of old age.

The examples which I have brought together show that often amongst vertebrates there are some animals the organisms of which withstand the ravages of time much better than that of man. I think it a fair inference that senility, the precocious senescence which is one of the greatest sorrows of humanity, is not so profoundly seated in the constitution of the higher animals as has generally been supposed. It is not necessary, therefore, to discuss at length the general question as to whether senile degeneration is an inevitable event in living organisms.

I have already shown, in the “Nature of Man,” the difference which exists between senile degeneration in our own bodies and the phenomena of senescence amongst Infusoria which, as M. Maupas described, are followed by a process of rejuvenescence. According to the more recent results of several investigators, the difference is still greater than I had supposed. Enriquez[4] has been able to propagate Infusoria to the 700th generation without any sign of senility being displayed. Here we are far from the condition in the human race.

R. Hertwig,[5] one of the best observers of the lower animals, has recently attempted to show that the very simple animalculæ of the genus _Actinosphærium_ are subject to true physiological degeneration. He has several times seen cultures of this Rhizopod degenerate, until all the individuals had died, notwithstanding the presence of abundant food. Prof. Hertwig attributed this to the “constitution of the _Actinosphærium_ having been weakened by too great vital activity at an earlier stage.” I should have thought that it was a much more natural explanation to suppose that the culture had undergone infection by one of the contagious diseases which so often destroy cultures of different kinds of lower animals and plants. As this idea had not occurred to the observer, he had not searched for parasitic microbes amongst the granulations which are always present in the body of an _Actinosphærium_. However this may be, I cannot accept the facts brought forward by this distinguished German as a valid proof of the existence of senile degeneration in these lowly creatures.

The facts that I have brought together in this chapter justify the conclusion that human beings who reach extreme old age may preserve their mental qualities notwithstanding serious physical decay. Moreover, it is equally plain that the organism of some vertebrates is able to resist the influence of time much longer than is the case with man under present conditions.

II

THEORIES OF CAUSATION OF SENILITY

Hypothesis of the causation of senility—Senility cannot be attributed to the cessation of the power of reproduction of the cells of the body—Growth of the hair and the nails in old age—Inner mechanism of the senescence of the tissues—Notwithstanding the criticisms of M. Marinesco, the neuronophags are true phagocytes—The whitening of hair and the destruction of nerve cells, as arguments against a theory of old age based on the failure of the reproductive powers of the cells

Although it has not been proved that living matter must inevitably undergo senile decrepitude, it is none the less true that man and his nearest allies generally exhibit such degeneration. It is therefore extremely important to recognise the real causes of our senescence. There have been many hypotheses on the subject, but there are comparatively few definite facts known.

Bütschli has supposed that the life of cells is maintained by a specific vital ferment which becomes feebler in proportion to the extent of cellular reproduction, but I cannot regard this as more than a pious opinion. The ferment has never been seen, and we do not know of its actual existence. According to the better-known theory of Prof. Weismann, old age depends on a limitation in the power of cells to reproduce, so that a time comes when the body can no longer replace the wastage of cells which is an inevitable accompaniment of life. As old age appears at different times in different species and different individuals, Weismann has concluded that the possible number of cell generations differs in different cases. He has not found, however, a solution of the problem as to why multiplication of cells should cease in one individual, whereas it proceeds much further in other individuals. Prof. Minot,[6] the American zoologist, has developed a similar theory, and has employed an exact method to determine the gradual diminution in the rate of growth of an animal from its birth onwards. According to him, the power of reproduction of the cells weakens progressively during life, until a point is necessarily reached at which the organism, no longer capable of repairing itself, begins to atrophy and degenerate. Dr. Buehler[7] has recently laid stress upon this theory.

There is no doubt that cells reproduce much more actively during the embryonic period. The process becomes slower later on, but, none the less, continues to display itself throughout the whole period of life. Buehler attributes the difficulty with which certain wounds heal in the case of old people to the insufficiency of cellular reproduction. He thinks in particular that the proliferation of the cells of the skin, to replace those which are worn off from the surface, becomes less active with age. According to him, it is theoretically obvious that a time must come when the replacement of the epidermic cells completely ceases. As the superficial layers of the skin continue to dry up and be cast off, it is plain that the epidermis must disappear completely. Buehler thinks that there must be a similar fate for the genital glands, the muscles, and all the other organs.

These theoretical considerations, however, are not compatible with certain well-known facts indicating that there is no general cessation of the power of cell reproduction in old age. The hairs and the nails, which are epidermic outgrowths, continue to grow throughout life, their growth being due to the proliferation of their constituent cells. There is no sign of any arrest in the development of these structures, even in the most advanced old age. The reverse is true. It is well known that the hairs on some parts of the body increase in number and in length in old people. In some lower races, for instance in the Mongols, the moustache and the beard grow vigorously in old age, whilst young people of the same race have only very small moustaches and practically no trace of beard. So also in white women the fine and almost invisible down which covers the upper lip, the chin, and the cheeks in the young may become replaced by long hairs which form a moustache or beard.

Dr. Pohl, a specialist in the growth of hair, has measured the rate of growth in different circumstances. He has shown that in an old man of 61 the hair on the temple grew 11 mm. in a month; on the other hand, the hair on the same region in boys of 11 to 15 years old grew in the same time only from 11 to 12 mm. Plainly, there is no case here of a progressive diminution of cell-proliferation with age. The same observer, it is true, has shown that the hair of young men of between 21 and 24 years grew at the rate of 15 mm. a month, whilst in the same individuals, at the age of 61 years, the rate of growth was only 11 mm.; but this diminution in the rate of growth is only apparent. The first figure concerned the hair taken from different regions of the scalp, whilst the second related only to the hair on the temples, and Dr. Pohl himself has shown that, in the latter region, the hair grows slower than in other regions. Moreover, in many boys of 11 to 15 years old, studied by this observer, the rate of growth was always less than 15 mm., and often less even than the 11 mm. recorded in the old man of 61.

I have been able to note that the nails grow even in very old people. In the case of Mme. Robineau, the centenarian, the nail of the middle finger of the left hand grew 2-1/2 mm. in three weeks. In the case of a lady of 32 years old, the corresponding nail grew 3 mm. in two weeks, the difference being out of all proportion to the enormous difference in the age. The centenarian’s nails had to be cut from time to time.

Although the hairs of old people grow, they become white, which is a phenomenon of senile degeneration. Although they increase in length, the colouring matter in them becomes reduced and finally disappears. In the “Nature of Man” I described the process by which this blanching takes place, and which may now be regarded as definitely proved. It is useful as a means of interpreting the real nature of the process of senescence. In several published works, I have explained my belief that just as the pigment of the hair is destroyed by phagocytes, so also the atrophy of other organs of the body, in old age, is very frequently due to the action of devouring cells which I have called macrophags. These are the phagocytes that destroy the higher elements of the body, such as the nervous and muscular cells, and the cells of the liver and kidneys. This part of my theory has encountered very strong criticism, especially with regard to the part played by the macrophags in the senescence of nervous tissue.

Neurologists in particular, have criticised my interpretation. For several years M. Marinesco[8] has attacked my theory of the atrophy of the nerve-cells in old age. In the first place, he has stated that in old people, and even if these are very old, it is rare to find phagocytes surrounding and devouring the cells of the brain. In support of this contention, he has been good enough to send me two preparations made from the brains of two very old persons. After careful examination I was convinced that my opponent had been inexact. In the brain of the two centenarians (one of whom died at the age of 117 years) there were very many nerve-cells surrounded by phagocytes and in process of being destroyed by them. It happened, however, that as the sections were very weakly stained, it was more difficult to observe the facts than in the preparations upon which I had made my own observations. I have already recorded this fact in the second and third French editions of the “Nature of Man.”

Without taking notice of my reply, M. Marinesco has published another criticism of my theory in an article[9] entitled “Histological Investigations into the Mechanism of Senility.” In that work, although he himself had invented the designation “neuronophag” for a phagocyte that devours nerve-cells, he denies the existence of such a power. He thinks that nerve-cells atrophy independently of the cells that surround them. The latter, the so-called neuronophags, only contribute to the atrophy inasmuch as they press against the nerve-cells and deprive them of nutrition. He is confident that the constituent parts of nerve-cells are never found in the neuronophags. There is no question of phagocytosis, of the existence of cells that devour their neighbours.

M. Léri has taken a similar view in a Report on the Senile Brain[10] presented to a recent congress of alienists and neurologists. According to him “the nuclei which surround some of the atrophying nerve-cells do not play the part of neuronophags.” In his monograph “La Neuronophagie,”[11] M. Sand elaborates the same view. He relies on his observation that “neuronophags are usually either devoid of protoplasm or display only a very thin layer of it. They never exhibit protoplasmic outgrowths, and they never have granules in their cellular bodies (p. 86).” Still more recently MM. Laignel-Lavastine and Voisin[12] have taken the same view, maintaining that the neuronophags do not display phagocytosis.

Although I cannot undertake here to give a detailed reply to the arguments of my critics, I may point out a fallacy that vitiates their reasoning. The study of the intimate structure of nervous tissue involves the treatment of that very delicate substance by numerous active reagents. It is extremely important not to forget the possibility of alterations which may be produced in the processes of preparation and which are extremely difficult to avoid. A glance at the figures given by my critics shows me that the neuronophags in their preparations had been subjected to violent treatment. When M. Léri speaks of “the nuclei which surround some of the nerve-cells,” and M. Sand of “cells without protoplasm,” it is clear that they had been observing cells destroyed by the processes of the laboratory. The illustrations in the memoir of M. Marinesco show that in his preparations, too, the neuronophags had been very greatly altered.

It is well known that nuclei do not exist free in tissues, and that when they appear devoid of protoplasm, there has been some defect in the technical methods of preparing them for examination. As a matter of fact, neuronophags do not consist of nuclei with at the most a pellicle of protoplasm; like other cells, they have protoplasmic bodies which, however, are frequently destroyed by the violent processes of histological preparation.

The arguments of my critics recall to me the words of a medical student, who, on being asked to describe the microbe of tuberculosis, said that it was a little red bacillus. The bacillus in question, like most bacilli, is colourless, but it is usual to stain it so that it may be visible under the microscope. The student, knowing it only in particular preparations, had a false idea of its appearance.

In well-made preparations, neuronophags are typical cells with abundant protoplasm. When they have been preserved by a process that does not dissolve their contents, they show granules like those found in nerve-cells.

To study neuronophagy, M. Manouélian,[13] in the laboratory of the Pasteur Institute in Paris, set himself to improve the technical methods of preparation. He succeeded in showing first that in the destruction of nerve-cells that occurs in cases of hydrophobia, the contents of these cells are absorbed by the surrounding neuronophags. “My observations on the cerebro-spinal ganglia of human cases of hydrophobia,” he wrote, “show clearly that the macrophags act as phagocytes of the nerve-cells.” “Most of the cells in the nerve-ganglia contain yellow, brown, and black pigmented granules, usually united in small masses. What becomes of these granulations on the destruction and disappearance of the nerve-cell? If, as M. Marinesco has it, there is no phagocytosis by the surrounding cells, but merely a mechanical interference, then the granules, on the destruction of the nerve-cells that contained them, should be found lying in the interstitial tissue. But this does not happen. The granules are ingested by cells which are true macrophags.”

By the aid of a very delicate mode of preparation, M. Manouélian has shown that in the case of senile brains the granules of the nerve-cells are absorbed by neuronophags. I have myself studied M. Manouélian’s preparations and can testify to the accuracy of his observations (Figs. 6 and 7).

Doubt is no longer possible. In senile degeneration the nerve-cells are surrounded by neuronophags which absorb their contents and bring about more or less complete atrophy. It has been supposed that in order to devour their contents, the neuronophags must penetrate the nerve-cells, and such an event has rarely been seen. But it is well known, the phagocytosis of red blood corpuscles being a typical instance, that to absorb a cell a phagocyte does not necessarily engulf it bodily or penetrate it, but may gradually denude it of its contents merely by resting in contact with it.

There has been some discussion as to the condition of nerve-cells which are on the point of being devoured by neuronophags. It has been noticed that such cells may display a considerable amount of degeneration without being devoured, whilst, on the other hand, cells apparently normal have been found undergoing phagocytosis. As I cannot state definitely what are the conditions that induce the phagocytosis of nerve-cells, I shall not attempt a discussion of the problem.

Although the destruction of nerve-cells by neuronophags is a general occurrence in senile brains, one may conceive of cases where this does not occur. And so, in old people who have preserved their faculties, it may well be that the neuronophags have refrained from attacking the nerve-cells. But as such instances are rare, so also phagocytosis is usually found in senile brains, and I cannot accept M. Sand’s denial of its existence, based on his study of two cases.

The general result of my investigation into the criticisms that have been published on this matter has confirmed me in my belief that neuronophagy plays a most important part in senescence, and recent observations that I have made with M. Weinberg have completely supported this view.

The bleaching of hair and the atrophy of the brain in old age thus furnish important arguments against the view that senescence is the result of arrest of the reproductive powers of cells. Hairs grow old and become white without ceasing to grow. The cessation of the power of reproduction cannot be the cause of the senescence of brain-cells, for these cells do not reproduce even in youth.

III

MECHANISM OF SENILITY

Action of the macrophags in destroying the higher cells—Senile degeneration of muscular fibres—Atrophy of the skeleton—Atheroma and arterial sclerosis—Theory that old age is due to alteration in the vascular glands—Organic tissues that resist phagocytosis

The instances which I have selected in attempting to describe the mechanism of senescence of the tissues are not the only cases in which the importance of phagocytosis is evident. The blanching of hair is due to the destructive agency of chromophags; in atrophy of the brain neuronophags destroy the higher nerve-cells. In addition to these instances of phagocytosis, in which the active agents belong to the category of macrophags, there are many other devouring cells, adrift in the tissues of the aged, and ready to cause destruction of other cells of the higher type. The phagocytic action is not so manifest as in the case of infectious diseases, partly because it is the method of macrophags to absorb the contents of the higher cells extremely slowly. The mode of action is well seen in the atrophy of an egg-cell (Fig. 8), where the surrounding macrophags gradually seize hold of the granules within it and carry these off. As the process goes on, the ovum becomes reduced to a shapeless mass, and finally leaves only a few fragments, or disappears completely. M. Matchinsky[14] has studied the series of events in my laboratory, and I am myself well assured of the importance of the action of macrophags in the atrophy of the ovary.

The phenomena of atrophy in general and of senile decay afford other cases of tissue destruction in which the phagocytic character of the process is more modified and obscure than in nerve-cells and ova.

It is well known that progressive muscular debility is an accompaniment of old age. Physical work is seldom given to men over sixty years of age, as it is notorious that they are less capable of it. Their muscular movements are feebler and soon bring on fatigue; their actions are slow and painful. Even old men whose mental vigour is unimpaired admit their muscular weakness. The physical correlate of this condition is an actual atrophy of the muscles, and has for long been known to observers. More than half a century ago, Kölliker,[15] one of the founders of histology, devoted some attention to this matter, and described the senile modification of muscular tissue in the following words:—“In old age there is a true atrophy of the muscles. The fibres are much more slender; there are deposited in their substance numerous yellow or brown granules and many globular nuclei. These nuclei are frequently arranged in longitudinal series and present such signs of active division as are found in embryonic tissue.”

Other investigators afterwards made similar observations. Vulpian[16] and Douaud[17] have stated that a multiplication of nuclei takes places in the atrophying muscles of the old.

As the senile degeneration of muscular tissue appeared to be important in my study of the mechanism of senescence, M. Weinberg and I examined several cases of muscular atrophy in old human beings and lower animals. We were able to recognise the phenomena observed by our predecessors. In senile atrophy the muscular fibres contain many nuclei, and these, increasing rapidly, bring about an almost complete disappearance of the contractile substance (Fig. 9). The fibres preserve their striation for a certain time but eventually lose it and appear to contain an amorphous mass with numerous, rapidly multiplying nuclei.

The investigators who had recorded these facts thought of them only as curious. It is plain, in the first place, however, that this remarkable and rapid multiplication is a proof that senile atrophy is not due to failure of cell proliferation, although the latter has frequently been suggested as the mechanism of senescence. In muscular atrophy, cell multiplication, so far from failing, greatly increases. We may add muscular atrophy to the blanching of hair and the decay of nerve-cells as another instance showing that senile degeneration is not the result of cells ceasing to be able to multiply. Just as in the atrophy of the brain there is an increase in the volume of neuroglœa, the substance in which the neuronophags are found, so also in the atrophy of the muscles there is an increase of muscular nuclei. Along with the increase of nuclei, however, there is an increase of the protoplasmic substance of the fibres known as sarcoplasm. The latter replaces the myoplasm, the specific striated substance of muscles, by a process which must be regarded as parallel with phagocytosis. In a normal muscle the two substances and the sarcoplasmic nuclei are in equilibrium, but in old age the sarcoplasm and its nuclei increase at the expense of the myoplasm. The equilibrium is destroyed with the result that the muscular power is weakened. In these conditions the sarcoplasm acts phagocytically with regard to the myoplasm, just as the chromophag becomes the phagocyte of the pigment of the hair, or the neuronophag devours the nerve-cell.

The investigation of other cases of muscular atrophy, as, for instance, that of the caudal muscles of frog-tadpoles, confirms the significance of the process that I have observed in old age. In the two cases, what takes place is the destruction of the contractile material of the muscles by myophags, a special kind of phagocyte.

It is one of the curiosities of senile atrophy that whilst there is hardening or sclerosis of so many organs, the skeleton, the most solid part of our frame-work, becomes less dense, so that the bones are friable, the condition often leading to serious accidents in old people. The bones become porous, and lose weight. It is difficult to believe that macrophags, although they destroy softer elements such as nerve-cells or muscle fibres, can be able to gnaw through a hard material like bone impregnated with mineral salts. As a matter of fact, the mechanism of bone atrophy must be placed in a different category from the phagocytosis of other organs. It is brought about, however, by the agency of cells very like some of the macrophags. These cells contain many nuclei, and are known as osteoclasts. They form round about the bony lamellæ and lead to their destruction, but are incapable of breaking off fragments of bone and dissolving them in their interiors. Although the intimate mechanism of this destructive action is not thoroughly understood, it seems probable that the cells secrete some acid which softens bone by dissolving the lime salts. The process can be observed in the different varieties of caries of the bone, and in the bony atrophy of old age as is represented in Fig. 10.

By the action of the osteoclasts, which themselves are macrophags, part of the lime in the skeleton is dissolved during old age and passes into the general circulation. This is probably a source of the lime which is deposited so readily in the different tissues of old people. Whilst the bones become lighter, the cartilages become bony, the inter-vertebrate discs in particular becoming impregnated with salts, so that the well-known senile malformation of the backbone is produced.

As a result of this displacement of lime in old age, the blood-vessels become modified in a distinctive fashion. Atheroma of the arteries is not invariable in old people, but it occurs extremely frequently. In this form of degeneration, lime salts are deposited in the walls of the cells, so that they become hard and friable. Several others, among whom I may mention Durand-Fardel and Sauvage, have laid stress on the coincidence of atheromatous lesions of the arteries and senile degeneration of the bones. The relations between the two alterations are very evident in the skull; the meningeal artery becomes sinuous and atheromatous, and the grooves on the inner side of the bones of the skull in which it runs, flatten out, and become larger because of other malformations.[18]

There is no disharmony in the nature of old people so striking as this transference of the lime salts from the skeleton to the blood-vessels, producing as it does a dangerous softening of the former, and a hardening of the latter that interferes with their function of carrying nutrition to the organs. It is the manifestation of an extraordinary disturbance of the properties of the cells that compose the body. The atheromatous condition of the arteries is closely linked with arterial sclerosis, an affection which is very common, although not constant, in the aged. The whole question of these vascular alterations is extremely complex, and before it can be cleared up, a number of special investigations must be made.

Probably diseases of the arteries of different kinds, and arising from different causes, are grouped under the terms atheroma and sclerosis. In some cases the lesions are inflammatory and are due to the poisons of microbes. An example of such an origin is the case of syphilitic sclerosis, in which the specific microbes (spirilla of Schaudinn) lead to precocious senescence. In other cases the arteries show phenomena of degeneration resulting in the formation of calcareous platelets which interfere with the circulation of the blood.

Investigations which have been made in recent years have led to very interesting results concerning the origin of atheroma of the arteries. In most cases, attempts to produce such lesions of the arteries by experimental methods have not succeeded, but M. Josué[19] has been able to produce true arterial atheroma in rabbits by injecting into them adrenaline, the secretion of the supra-renal capsules.

This experiment has been repeated many times and is now well known. Later on, M. Boveri[20] obtained a similar result by injecting nicotine, the poison of tobacco. It is obvious, therefore, that amongst the arterial diseases which play so great a part in senescence, some are chronic inflammations produced by microbes, whilst others are brought about by poisons introduced from without.

It is easy to understand, therefore, why these diseases of the arteries are not always present in old age, although they are very common.

The part played by the secretion of the supra-renal glands in the production of arterial disease has brought renewed attention to a theory which supposed that certain glandular organs in the body play a preponderating part in senile degeneration. Dr. Lorand[21] in particular has argued that “senility is a morbid process due to the degeneration of the thyroid gland and of other ductless glands which normally regulate the nutrition of the body.” It has long been noticed that persons affected with myxodema, as a result of the degeneration of the thyroid gland, look like very old people. Everyone who has seen the cretins in Savoy, Switzerland, or the Tyrol, must have noticed the aged appearance of these victims, although very often they are quite young. The condition of cretinism, with its profound bodily changes, is the result of degeneration of the thyroid gland. On the other hand, it is well known that in old people the thyroid and the suprarenals frequently show cystic degeneration. It is quite probable, therefore, that these so-called vascular glands have their share in producing senility. Many facts show that they destroy certain poisons which have entered the body, and it is easy to see that, if they have become functionless, the tissues are threatened with poisoning. It does not follow, however, that their action in producing senility is exclusive, or even preponderating. M. Weinberg, at the Pasteur Institute, made special investigations on this point, and found that the thyroid gland and the supra-renal capsules were almost invariably normal in old animals (cat, dog, horse), although the latter showed unmistakable signs of senility. Similarly in an old man of 80 years, who died from pneumonia, the thyroid gland was quite normal.

It must not be forgotten that the aged very often die from infectious diseases such as pneumonia, tuberculosis, and erysipelas. In these diseases the vascular glands generally, and the thyroid gland in particular, are very often affected, with the result that what is due to infection has been set down as a symptom of old age.[22]

Although the appearance of patients from whom the thyroid gland has been removed, or in whom it has degenerated spontaneously, recalls that of old people, it is possible to exaggerate the similarity. In the masterly accounts of such unfortunates, recently compiled by the well-known surgeon Kocher[23] there are many points which are characteristic, without being typical, of old people.

Oedema of the skin which characterises thyroid patients is by no means usual in old age. The loss of hair, normal in the patients, is not a character of old age. In myxedematous women, menstruation is very active; it ceases in old women. The great muscular development of myxedematous patients distinguishes them from old people.

Physiological investigation does not support the existence of any strong affinity between old age and affection of the thyroid gland. It is known that removal of the thyroid is followed by cachexia only in young subjects, MM. Bourneville and Bricon[24] having shown that the tendency to cachexia after extirpation of the thyroid ceases almost abruptly at the age of thirty. That age may be taken as the limit of youth, of the time when growth is vigorous and the function of the thyroid most active. Cases of cachexia, where the thyroid gland has been removed in old persons from fifty to seventy, are very rare.

Rodents (rats, rabbits) support the removal of the thyroid extremely well, without signs of cachexia, although these are normally short-lived creatures. According to Horsley[25] extirpation of the thyroid is not followed by cachexia in birds or rodents and is followed by it only very slowly in ruminants and horses; it produces the condition invariably but slightly in man and monkeys and extremely seriously in carnivora. If this series be compared with the information given in the next section of this volume on the relative ages which the animals in question attain, it will be seen that there is no correspondence.

In short, whilst I do not deny that the vascular glands may take a share in the causation of senility, in so far as they are destroyers of poisons, I cannot agree with the theory of Dr. Lorand.

I think it indubitable that in senescence the most active factor is some alteration in the higher cells of the body, accompanied by a destruction of these by macrophags which gradually usurp the places of the higher elements and replace them by fibrous tissue. Such a process affects the organs of secretion (kidneys), the reproductive organs, and in a modified form the skin, the mucous membranes, and the skeleton. The testes are amongst the organs which resist invasion by macrophags. I have already given an example (“The Nature of Man,” p. 98) of an old man of 94 in whom active spermatozoa were produced. I know of a similar case, the age being 103 years. Such cases are not rare, and not only in old men, but in old animals, the testes continue to be active. Dr. Weinberg and I have investigated these organs in a dog which died at the age of 22 years after several years of pronounced senility. Many of the organs of the animal exhibited serious invasions by macrophags but the testes were extremely active, the cells being in free proliferation and producing abundant spermatozoa (Fig. 11). In harmony with this condition of the sexual organs, the sexual instincts of the animal remained normal. We have investigated another dog which died at the age of eighteen years. In this case the testes were cancerous and there was no possibility of the production of spermatozoa. None the less, this dog although markedly senile (Fig. 12) still showed sexual instincts until shortly before it died.

It is manifest that the tissues do not invariably degenerate in old age, nor do all the organs that are modified in old age show destruction by phagocytes and replacement by connective tissue. Organs which produce phagocytes, such as the spleen, the spinal marrow and the lymphatic glands, certainly show traces in old age of fibrous degeneration but remain sufficiently active to produce macrophags which destroy the higher cellular elements of the body. I have frequently noticed cell division in such organs, and as an example may give the case of the bone marrow taken from a man of 81 years (Fig. 13).

The eye is an organ that is modified in old age without the action of macrophags. Cataract and the senile arc which appears as a milky ring at the edge of the cornea are frequent in old age. These modifications are due to impregnation of the parts affected by fatty matter which makes them opaque. This deposition of fat[26] has been attributed to defective nutrition. In most organs such fatty degeneration is followed by phagocytosis, but the cornea and the crystalline lens are exempt from this consequence for anatomical reasons. Most organs possess in addition to their higher elements a constant source of macrophags. Such a source of phagocytosis is the neuroglœa in nervous tissues, the sarcoplasm in muscular tissues; the bones contain osteoclasts and the liver and the kidneys are readily invaded by phagocytes from the blood. The lens and the cornea have no cells that are able to become macrophags.

Some infectious diseases bring about precocious senility. A syphilitic child is “a miniature old man, with wrinkled face, skin dull and discoloured and flabby and hanging in folds as if it were too large.”[27] In such a case the active agent is the microbe of syphilis which has poisoned the child on the breast of its mother. It is no mere analogy to suppose that human senescence is the result of a slow but chronic poisoning of the organism. Such poisons, if not completely destroyed or eliminated, weaken the tissues, the functions of which become altered or enfeebled, so that, amongst other changes, there is deposition of fatty matter. The phagocytes resist the influence of invading poisons better than any of the other cells of the body and sometimes are stimulated by them. The general result of such conditions is that there comes to be a struggle between the higher cells and the phagocytes in which the latter have the advantage.

The answer to the question as to whether our senescence can be ameliorated must be approached from several points of view. This course I shall now follow.