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 Lankester3 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. Enriquez4 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. Buehler7 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. Marinesco8 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 article9 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 Brain10 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 Voisin12 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. Matchinsky14 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.

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. Vulpian16 and Douaud17 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. Josué19 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. Boveri20 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. Lorand21 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 supra-renals 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 Kocher23 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 Bricon24 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 Horsley25 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. Testis tissue from a dog Fig. 11.—Testis tissue from a dog aged twenty-two years.
(From a preparation made by Dr. Weinberg.) 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 fat26 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 Fig. 13.—Bone marrow from the sternum of a man aged eighty-one years.
(From a preparation made by Dr. Weinberg.) 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.

PART II

LONGEVITY IN THE ANIMAL KINGDOM

I

THEORIES OF LONGEVITY

Relation between longevity and size—Longevity and the period of growth—Longevity and the doubling in weight after birth—Longevity and rate of reproduction—Probable relation between longevity and the nature of the food

The duration of the life of animals varies within very wide limits. Some, as for instance, the males of certain wheel animalculæ (Rotifera) complete their cycle of life from birth to death in 50 or 60 hours, whilst others, like some reptiles, live more than 100 years, and quite possibly may live for two or three centuries.

Enquiry has been made for many years as to whether there are laws governing these different durations of life. Even the most casual observation of domesticated animals has shown that, as a general rule, small animals do not live so long as large ones; mice, guinea pigs, and rabbits for instance, have shorter lives than geese, ducks, and sheep, whilst these again are survived by horses, deer, and camels. Of all the mammals which have lived under the protection of man, the elephant is at once the largest, and the most long-lived.

However, it is not difficult to show that there is no absolute relation between size and longevity, since parrots, ravens, and geese live much longer than many mammals, and than some much larger birds.

As a general rule it may be said that a large animal takes more time than a small one to reach maturity, and it has been inferred from this that the length of the periods of gestation and of growth were in proportion to the longevity. Buffon28 long ago stated his opinion that the “total duration of life bore some definite relation to the length of the period of growth.” Therefore, as the period of growth is, so to say, inherent in the species, longevity would have to be regarded as a very stable phenomenon. Just as any species has acquired a fixed and practically invariable size, so it would have acquired a definite longevity. Buffon, therefore, thought that the duration of life did not depend on habits or mode of life, or on the nature of food, that, in fact, nothing could change its rigid laws, except an excess of nourishment.

Taking as his standard the total period of development of the body, Buffon came to the conclusion that the duration of life is six or seven times that of the period of growth. Man, for instance, he said, who takes 14 years to grow, can live 6 or 7 times that period, that is to say, 90 or 100 years. The horse, which reaches its full size in 4 years, can live 6 or 7 times that length of time, that is to say from 25 to 30 years. The stag takes 5 or 6 years to grow, and reckoned in the same way, its longevity should be 35 to 40 years.

Flourens29 although supporting his principle, thought that Buffon had been inexact in calculating the period of growth. In his opinion a better result can be obtained by taking the limit of growth as that age at which the epiphyses of the long bones unite with the bones themselves. Using such a mode of computation, Flourens laid down that an animal lived 5 times the length of its period of growth. Man, for instance, takes 20 years to grow, and he can live for 5 times that space, that is to say, 100 years; the camel takes 8 to grow, and lives 5 times as long, i.e., 40 years; the horse, 5 to grow, and lives 25 years.

However, even if we consider only the mammalia, it is impossible to accept Flourens’ law, without considerable reserve. Weismann30 has referred to the case of the horse, which is completely adult at 4, but lives not merely 5 times that period, but 10 or even 12 times. Mice grow extremely quickly, so that they are able to reproduce at the age of 4 months. Even if we take 6 months as their period of growth, their longevity of 5 years is twice as long as it would be according to the rule of Flourens. Amongst domesticated animals, the sheep is slow in reaching maturity; it does not acquire its adult set of teeth until it is 5 years old, and cannot be regarded as adult until then. None the less, at the age of 8 or 10 years, it loses its teeth and begins to grow old, whilst by 14 it is quite senile.31 The longevity of the sheep, therefore, is not quite three times its period of growth.

If we turn to other vertebrates, the variations in the relation of growth and the duration of life are still greater. Parrots, for instance, the longevity of which is extremely great, grow very quickly. At the age of 2 years, they have acquired the adult plumage and are able to reproduce, whilst the smaller species are in the same condition at the age of one. Incubation, moreover, is very short, not more than 25 days, and in some species not three weeks. None the less, parrots are birds which enjoy a quite remarkable longevity. The incubation period of domestic geese is 30 days, and their period of growth is also short. However, they may reach a great age, cases of 80 years and of 100 years being on record. In contrast with these, ostriches, the incubation period of which is 42 to 49 days, and which take 3 years to become adult, have a relatively short life.

H. Milne-Edwards32 many years ago contended that there was no importance in the supposed law of relation between gestation and longevity. He sums up his criticism as follows: “Although the period of uterine life is longer in the horse, that animal does not live so long as a human being; and some birds, the incubation of which only lasts a few weeks, can live more than a century.”

Bunge33 has recently taken up the study of the relations between the duration of growth and longevity, and has suggested a new means of investigation. He has observed that the period in which the new-born mammal doubles its weight is a good index of the rapidity of its growth. He has shown that whilst a human child requires 180 days to reach double its weight at birth, the horse, the longevity of which is very much less, doubles its weight in 60 days; a calf takes only 47 days for this; a kid 15 days; a pig 14 days; a cat 9-1/2; and a dog only 9 days. Although these facts are very interesting, the exceptions are too great to make it possible to base a law of longevity upon them. The period of weight-doubling in the horse is nearly 7 times longer than that in the dog, and yet the longevity of the horse is not more than 3 times that of the dog. The goat, which takes much longer than the dog to double its weight, has a shorter total life.

I observed myself that new-born mice quadruple their weight in the first 24 hours. The doubling of weight in their case requires a time 36 times less long than that of the cat, and yet the cat lives only 5 times as long as the mouse.

It is fair to say, however, that Bunge himself does not draw a definite conclusion from these figures and has published them only to stimulate interest in the subject. He is against the view of Flourens, and points out that although the multiple 5 is valid for man, it is not so in the case of the horse which finishes its growth in 4 years and yet reaches the age of 40 much less often than human beings attain that of 100 years.

Although it is impossible to admit the existence of exact relations between size and the period of growth on the one side, and longevity on the other, in the mode which Buffon and Flourens have followed, it is none the less true that there is something intrinsic in each kind of animal which sets a definite limit to the length of years it can attain. The purely physiological conditions which determine this limit leave room for a considerable amount of variation in longevity. Duration of life therefore, is a character which can be influenced by the environment. Weismann in his well-known essay on the duration of life, has laid stress on this side of the problem. Longevity, according to him, although in the last resort depending on the physiological properties of the cells of which the organism is composed, can be adapted to the conditions of existence and influenced by natural selection, like other characters useful for the existence of the species.

If a species is to remain in existence, its members must be able to reproduce and the progeny must be able to reach adult life so that they in their turn may reproduce. Now, it happens that there are some animals the fecundity of which is extremely limited. Most birds which are adapted to aerial life, and the weight of which is therefore to be kept down, lay very few eggs. This happens in the case of birds of prey, such as eagles and vultures. These birds nest only once a year, and generally rear two or frequently only a single nestling. In such circumstances the duration of life becomes a factor in the preservation of the species, more important since eggs and chicks are subject to many dangers. Eggs are devoured by many kinds of animals, whilst unseasonable cold may kill the chicks. If the members of such a species were incapable of living long, the unfavourable conditions of life would soon lead to extinction. Those animals which reproduce rapidly generally have a relatively brief duration of life. Mice, rats, rabbits, and many other rodents seldom live more than 5 or 10 years, but reproduce with enormous rapidity. It is almost possible to imagine that there is some sort of intimate link, possibly physiological, between longevity and low fertility. It is a current opinion that reproduction wastes the maternal organism and that mothers of many children grow old prematurely and seldom reach an advanced age. This would seem to mean that fecundity was the cause of the short duration of life. However, we must guard ourselves against such a theory. Longevity, at least in the case of vertebrate animals, differs extremely little in the two sexes, although the cost of the new generation to the adult organism is very much greater in the case of the female than of the male parent. None the less, females frequently reach a great age, especially in the human race where women reach 100 years, or live beyond that time, much more often than men.

Low fertility, however, cannot itself be regarded as a cause of longevity, as there are some very fertile animals which none the less attain great ages. There are parrots which lay two or three times a year, producing six to nine eggs in each clutch. The ducks (Anatidæ) are distinguished for considerable longevity and very high fertility, each nest containing rarely less than six and sometimes as many as sixteen eggs. The common Sheldrake lays from twenty to thirty eggs. Tame ducks, in some parts of the tropics, lay an egg daily throughout the season. Wild ducks lay from seven to fourteen eggs in one nest. Ducks and geese, none the less, frequently attain considerable ages, ducks having been known to live for 29 years. Even the common fowl, which is a notoriously prolific bird, may reach an age of twenty to thirty years.

It will be said, however, that these birds are exposed to many enemies during youth. Chickens, ducklings, and goslings are ready prey for hawks, foxes and small carnivora. The longevity is possibly to be explained as an adaptation for the preservation of the species by compensating for the great destruction of the young. Weismann explains in this way the longevity of many aquatic birds and other creatures that are much preyed on. It must be noted, however, that the longevity cannot depend on the risks run by the young birds, but must have arisen independently. If this had not occurred, creatures, the young of which are destroyed in great numbers, would have ceased to exist, as many species have disappeared in geological time. The longevity of prolific animals, the young of which are destroyed in numbers, must be due to some cause which is neither fertility nor the destruction of their offspring. This cause must be sought in the physiological processes of the organism and can be attributed neither to the length of the period of growth nor to the size attained by the adults.

After having discussed various theories of the cause of the duration of life, M. Oustalet,34 in a most interesting essay on the longevity of vertebrates, came to the conclusion that diet was the chief factor. He thinks that there is a “definite relation between diet and longevity. For the most part herbivorous animals live longer than carnivorous forms, probably because the former find their food with ease and regularity, whilst the latter alternate between semi-starvation and repletion.” There are certainly many instances which give support to the view. Elephants and parrots, for instance, are vegetarian and reach very great ages. On the other hand, there exist long-living carnivorous animals. Many observations have made it certain that owls and eagles reach great ages, and these birds live on animal food. Ravens, which live on carrion, are also notorious for the duration of their lives. There is no exact knowledge as to the ages reached by crocodiles, but although these live on flesh, it is certain that their longevity is great.

We must seek elsewhere for the real factors that control duration of life. Before stating my conclusion, I will review what is known as to the duration of life of different animals.

II.

LONGEVITY IN THE ANIMAL KINGDOM

Longevity in the lower animals—Instances of long life in sea-anemones and other invertebrates—Duration of life of insects—Duration of life of “cold-blooded” vertebrates—Duration of life of birds—Duration of life of mammals—Inequality of the duration of life in males and females—Relations between longevity and fertility of the organism

It is wonderful to what an extent the duration of life varies amongst animals, the slightest examination of the facts showing that very many factors must be involved.

As the higher animals are nearly always larger than invertebrates, if there be a definite relation between longevity and size, one would expect to find that vertebrates live longer than invertebrates. However, this is not the case. Amongst animals of extremely simple organisation, there are some which reach a great age. A striking example of this is found in sea-anemones. These animals have a very simple structure, without a separate digestive canal, and with a badly developed, diffused nervous system, and yet have lived very long in captivity. More than forty years ago, I remember having seen in the possession of M. Lloyd, the Director of the Aquarium at Hamburg, an anemone that he had kept alive for several dozen years in a glass bowl. Another sea-anemone, belonging to the species Actinia mesembryanthemum, is known to have lived 66 years. It was captured in 1828 by Dalyell, a Scottish zoologist, and was then quite adult, and probably about 7 years old. It survived its owner for 36 years, and died in Edinburgh in 1887, the cause of death being unknown. Although they are thus capable of living so long, the rate of growth of members of this species is rapid, and their fertility is very high. According to Dalyell, these anemones reach the adult condition in 15 months. The specimen in his possession, in the 20 years from 1828 to 1848 produced 334 larvæ, then after a period of sterility it gave birth, in one night (1857) to 230 young anemones. This extraordinary prolificness decreased with age, but even when it was 58 years old it used to produce from 5 to 20 at a time. In the seven years from 1872 onwards, it gave birth to 150 young anemones.35 This animal, which certainly was not more than the fortieth or the fiftieth of the weight of an adult rabbit, lived six or seven times as long.

Ashworth and Nelson Annandale have published their observations on another sea-anemone, of the species Sagartia troglodytes, which was 50 years old. It differed from younger examples only in being less prolific.

There are other polyps, such as Flabellum, which do not live more than 24 years, although we have no knowledge as to the cause of the different duration of life.

The variation in the length of the life of molluscs and insects is extremely great. Some species of gasteropods (Vitrina, Succinea) live only a very few years, whilst others (Natica heros) can reach thirty years. Some of the marine bivalves, as for instance, Tridacna gigas, can live to sixty or a hundred years.36

Insects are animals as variable in their duration of life as they are in other respects. Some live only a few weeks; some of the plant-lice, for instance, die in a month. In the same order of Insects, however, (Hemiptera) there are species of cicada which live thirteen to seventeen years, that is to say, much longer than such little Rodents as rats, mice, and guinea-pigs. The larva of an American species spends seventeen years buried in the ground in orchards, where it feeds on the roots of apple trees, and the species is known as Cicada septemdecim, because of this duration of life. In the adult stage the insect lives little more than a month, just time enough to lay the eggs, and bring into the world the new generation, which in its turn will not appear above ground until after another period of seventeen years.

Between these extremes of long and short life, there is to be found amongst insects almost every gradation of longevity. Science, in its present state, has failed to find any law governing these facts. Rules which hold good up to a certain point in the case of the higher animals break down in their application to insects. The large grasshoppers and locusts, for instance, live a much shorter time than many minute beetles. Queen bees, the fertility of which is very great, live two or three years and may reach a fifth year, whilst worker bees, which are infertile, die in the first year of their existence. Female ants, although these are small and extremely prolific, reach the age of seven years.37

We know so little about the physiological processes of insects, that we cannot as yet make even a guess at the cause of this great variation in their longevity. It is more probable that we shall find some explanation in the case of vertebrates concerning which we know much more.

Analysis of the facts shows that whilst in the evolution from fish to mammal there has been a great increase in complexity of organisation, there has at the same time been a reduction in the duration of life. As a general rule, it may be laid down that the lower vertebrates live longer than mammals.

The facts about the longevity of fish are not very numerous, but it seems clear that these animals reach a great age. The ancient Romans, who used to keep eels in aquaria, have noted that these fish would live for more than sixty years. There is reason to believe that salmon can live for a century, whilst pike live much longer. There is, for instance, the much quoted instance of the pike stated by Gessner to have been captured in 1230 and to have lived for 267 years afterwards. Carps are regarded as equally long lived, Buffon setting down their period of life as 150 years. There is a popular idea that the carp in the lakes at Fontainebleau and Chantilly are several centuries old, but E. Blanchard throws doubt on the accuracy of this estimate, inasmuch as during revolutionary times most of the carp were eaten when the palaces were overrun by the populace. There is no doubt, however, that the life of carp may be very long indeed. Not very much is known about the duration of life in batrachians, but it is certain at least that some small frogs may live twelve or sixteen years, and toads as many as thirty-six years.

More is known about the life of reptiles. Crocodiles and caymans, which are large and which grow very slowly, attain great ages. In the Paris Museum of Natural History there are crocodiles which have been kept for more than forty years without showing signs of senescence. Turtles, although they are smaller than crocodiles, live still longer. A tortoise has lived for eighty years in the garden of the Governor of Cape Town, and is believed to have reached the age of two hundred years. Another tortoise, a native of the Galapagos Islands, is known to be 175 years old, whilst a specimen in the London Zoological Gardens is 150 years old. A land tortoise (Testudo marginata) has been kept in Norfolk, England, for a century. I am informed that in the Archbishop’s palace at Canterbury, there is to be seen the carapace of a tortoise which was brought to the Palace in 1623 and which lived there for 107 years.38 Another tortoise, brought to Fulham by Archbishop Laud, lived in the Palace for 128 years. I have already referred to a specimen of Testudo mauritanica, the history of which is known for 86 years, but which is probably much older.

Very little is known as to the longevity of lizards and serpents, but it may be inferred from what I have said about other reptiles that reptiles as a class are able to reach great ages.

It is an easy inference that the great duration of life in cold-blooded animals is associated with the slowness of the physiological processes in these creatures. The circulation, for instance, is so slow, that the heart of a tortoise beats only 20 to 25 times in a minute. Weismann has suggested that one of the factors influencing the duration of life is the rapidity or slowness of the vital activities, the times taken by the processes of absorption and nutrition.

On the other hand, the blood is hot and the vital activities are rapid in birds, and yet birds may attain great ages. Although in the last chapter I gave a number of examples, the subject is so important that I propose to go further into details. The possibility of this is due to an admirable set of details brought together by Mr. J. H. Gurney.39 In his list, in which are included more than fifty species of birds, the lowest figures are from eight and a half to nine years (Podargus cuvieri, Chelidon urbica), and a duration of life so short is an exception, a period of from fifteen to twenty years being more common. Canaries have lived in captivity from 17 to 20 years, and goldfinches up to 23 years. Field larks have lived for 24 years, the Lesser Black-backed Gull 31 years and the Herring Gull 44 years. Birds of medium size may live for several dozens of years, whether they live on animal or on vegetable food, whether they are prolific or lay very few eggs. I will quote only a few instances. Of forty parrots the minimum and maximum ages were respectively 15 and 81 years, and the average 43 years. Without accepting the truth of the story mentioned by Humboldt according to which certain parrots survived an extinct race of Indians, at least we may be certain that great ages have sometimes been reached by these birds. Levaillant mentions a parrot (Psittacus erithaceus) which lost its memory at the age of 60 years, its sight at 90 years, and which died aged 93 years. Another individual, probably of the same species, is reported by J. Jennings to have reached the age of 77. Jones, Layard, and Butler are the authorities for instances of Sulphur-crested Cockatoos having reached respectively 30, 72 and 81 years. M. Abrahams states that an Amazon (Chrysotis amasonica) lived 102 years. I myself have observed two cases of great longevity in the same species of parrot. One of these birds died at the age of 82 years, apparently simply from old age, whilst the other, which was in my possession for several years before it died at the age of 70 to 75 years, was vigorous, showing no signs of senility, but died of pneumonia.

Mr. Gurney found that parrots were not the only birds capable of reaching a great age. One raven reached 69 years and another 50, an Eagle-owl (Bubo maximus) 68 years, another 53, a condor 52, an imperial eagle 56, a common heron 60, a wild goose 80, and a common swan 70 years. None of these examples approaches the legendary three centuries attributed to the swan, but it is evident that many different kinds of birds may attain great age. I can add some cases to those of Mr. Gurney. In the Royal Park at Schönbrunn, near Vienna, a white-headed vulture (Neophron percnopterus) died aged 118 years, a golden eagle (Aquila chrysaëtus) aged 104, and another aged 80 (according to Oustalet). Mr. Pycraft (Country Life, June 25th, 1904) reported that a female eagle, captured in Norway in 1829, had been brought to England and had lived for 75 years. In the last thirty years of its life, it had produced ninety eggs. The same writer mentions the case of a falcon having lived to 162 years.