Old Age of Cells and Carcinoma
The relation between ageing of the cells on the one hand and the development of carcinoma on the other hand is a subject of great interest. According to Karl Pearson’s[130] statistical enquiry the incidence of carcinoma reaches its maximum at the age of 46 years in women and 56 years in men; Lazarus-Barlow[131] concluded that the range of years over which cancer is likely to occur is practically the same in the two sexes, namely 46 to 64, and that among 4659 cases of malignant disease there were only 35, or 0·7 per cent, over 80 years of age.[132] The cancer age, therefore, coincides with the waning of maturity and the onset of old age; that carcinoma is rare in very old persons is also shown by the occurrence of one case only among 71 centenarians collected by Sir George Humphry. Laurent[133] considered that whereas longevity depends on a condition of vital equilibrium, the development of cancer is due to a want of this equilibrium, to a state of anarchy, and that the factors disposing to orderly vitality are conducive to longevity and antagonistic to the development of new growth. The reason why malignant growths are prone to appear with the onset of old age has naturally been the subject of much debate. According to Thiersch degeneration lessens the controlling influence normally exerted by connective tissue on epithelium, the inherent proliferative capacity of which then runs riot. Ribbert believed that from loss of resistance or diminution of surface tension in the connective tissues post-natal “rests” of epithelium were produced as the result of irritation and that these displaced cells then grew because there was no controlling opposition. Adami suggested a reversion of the highly specialized epithelial cells to a simpler form with powers of proliferation, the cumulative habit of growth taking the place of the habit of work, and practically anticipated the more modern view. According to Hastings Gilford[134] malignant disease is a premature cell senility and the result of the partial reversion of immature or adult cells to an embryonic or quasi-embryonic state. From a study of senescence in dogs Goodpasture[135] concludes that degenerative changes in the cells lead not only to death of some cells but to dedifferentiation of others, which, becoming simpler in structure and function, recover their juvenile power of growth in varying degrees, and that hence metaplasia and tumour growths occur as accidents of commencing old age. A little later Oertel[136] insisted on his view that cancer is not an embryonic reversion or a specific change in the cell but a phenomenon of senescence—a degenerative proliferation depending upon disturbances in the nucleus plasma relations, specifically upon the loss of nuclear chromosomes; from age or degeneration the tumour cell loses the higher functional chromosomes and retains the genetically older and more resistant ones controlling reproduction and vegetative activities; thus there arises a race of cells without the differentiation of undegenerated cells.
These various expressions of opinion would justify the conclusion that with the onset of old age the degenerative processes in the cells lead to the production of less specialized cells which have the compensating property of more vigorous growth, and that in certain circumstances, one of which is very probably a diminished power of resistance on the part of the surrounding tissues and another, and very important one, irritation in some form or another, riotous proliferation of the cells invades the adjacent parts. That the conditions necessary are usually local is strongly suggested by the appearance of the new growth at one spot only and by the frequent absence of recurrence after free removal. There may be a premature local senescence of the tissues, just as there is premature old age of the body generally, and this would explain the exceptional occurrence of malignant disease in early life or long before the usual time.
VI
NORMAL STRUCTURAL CHANGES IN OLD AGE
Physiological old age, namely a process of involution and atrophy uncomplicated by superimposed pathological changes, is extremely rare; pathological processes may initiate and hurry on a condition imitating old age, and indeed the morbid changes found after death in old people commonly show the lesions of past infections in addition to those of physiological involution, and the longer life lasts the greater the probability that changes due to disease will accumulate. It is therefore difficult to determine accurately where physiological involution ends and pathological lesions begin, and there has been much confusion between physiological old age and pathological senility. It must, on the other hand, be admitted that the ideal condition of physiological involution without some definite evidence of superadded pathological change hardly ever comes before us. In fact at the best old age is almost always but relatively physiological, in other words, as Metchnikoff wrote in 1903, there is at present, from the conditions of inharmonious environment, no chance of a really physiological old age and death for mankind. But the view that old age is invariably the accumulated product of multiple injuries due to infection and poisons, or that it is due to arteriosclerosis (Boerhaave, Haller, Demange) is an entirely different proposition and does not fit in with biological knowledge. While fully recognizing the difficulties an attempt may be made to tabulate the natural changes accompanying and responsible for old age, and to contrast them with the pathological changes commonly complicating the normal structural involution of the human body.
The general atrophy of old age, as grossly shown by loss of weight, does not proceed equally in all parts of the body. The supporting fibrous tissues of the body and organs certainly atrophy less than the nobler, because actively functional, cells of the organs; it is difficult to estimate the atrophy of the fibrous tissues, for from shrinkage of the parenchyma of organs and of muscles the fibrous framework stands out in greater prominence. Some proliferation or replacement fibrosis follows atrophy of the nobler tissues, and pathologically infection may cause fibrosis. But that the fibrous tissue does to some extent share in the general atrophy is rendered probable on the analogy of the change in the allied tissue of bone which undergoes rarefaction and thinning. The subcutaneous and perivisceral stores of fat diminish out of proportion to the fibrous supporting tissues around them. The place of the fat in the fat cells may be taken by fluid—serous atrophy—or the cells may simply revert to the condition of connective tissue cells. In passing it may be pointed out that it is curious that with the diminished metabolism of old age the stores of fat are not increased as they are in similar circumstances in adult life; Is it due to a widespread atrophy of the connective tissue cells that store fat? If so, an accumulation of fat in the liver might be expected, but this is not so. Possibly it is the result of deficient assimilation. The heart, as Councilman[137] has shown, is on the whole better preserved than the other organs; but it might well be argued that the existence of such a cardiac condition is a determining factor in the attainment of advanced age.
The skin is dry, thin, smooth, glossy from atrophy, inelastic like parchment, and is wrinkled from degeneration and disappearance of the elastic tissue, subcutaneous fat and muscular fibre. These changes are most advanced on the face, especially the forehead, and backs of the hands from exposure. The degeneration of the elastic fibres, recently studied by Kissmeyer and With,[138] gives a characteristic mesh-like appearance, depending on the rigid wrinkles, to the skin, which takes a yellow tint. The ivory pallor and coldness are due to the diminution in the capillaries; the skin may show areas of pigmentation and leucodermia—changes described by Sir Lenthal Cheatle as due to the wear and tear of life (biotripsy); in a woman aged 93 Salimbeni and Gery described almost complete disappearance of the papillae and of the collagen fibres. The pigmentation has been regarded as a means of protection, for there is a relation between it and malignant disease, the latter being prone to occur when pigmentation fails (Pringle[139]). These atrophic changes are far commoner on the backs than on the palms of the hands, and it is noteworthy that among Cheatle’s[140] 200 collected cases of malignant disease of the hand there was one only on the palm. The subcutaneous fat is diminished in amount, which is regarded by Sir Arbuthnot Lane, though not with any special reference to old age, as one of the many results of colonic toxaemia. The yellow fat contains excess of cholesterol. There is diminished secretion by the sweat and sebaceous glands, and from this cause and the diminished vascularity there is less loss of heat to correspond with the slower metabolism.
Hair.—Greying or whitening of the hair occurs commonly in old age, but not universally for some centenarians have retained the natural colour of the hair; coarse jet-black hair is specially prone to whiten early. The change in colour has been ascribed by Metchnikoff to the action of phagocytes (chromophages) which invade the roots of the hairs and carry off the pigment granules. Like the arcus senilis it may occur quite early in life and without any other indication of age, and is often hereditary; as the sage of Norwich wrote, “Hairs make fallible Predictions, and many Temples early Gray have outlived the Psalmist’s Period.”[141] Lord Bacon[142] indeed said, “Hasty gray hairs, without baldness, is a token of long time; contrarily, if they be accompanied by baldness.” But baldness is often due to seborrhoea and so only secondarily connected with advanced age. In some rare instances the hair already grey or white has been known to regain its normal colour; the late Sir Charles Cameron[143] recorded this event in his own life after an accident confining him to bed for some months in his eightieth year, and refers to the hair of a man aged 90 years returning to its original brown colour; cases were also reported by Graves.[144] Velasquez de Tarente[145] recorded an abbess who after an illness which promised to be fatal in her hundredth year had a crop of brown hair, and, like Sir Charles Cameron, put on weight. Four other cases are given by Sir John Sinclair[146] in persons aged 80, 104, 105, and 114 years. Baldness may be definitely due to thyroid insufficiency and not to atrophy of the hair follicles and sebaceous glands.
A pensioner aged 75, whom I saw with Major R. J. C. Thompson, in the Royal Hospital, Chelsea, with baldness and a grey beard, was given thyroid extract, as he was thought to have hypothyroidism; his general condition then improved wonderfully, and his scalp became covered with dark brown hair which had to be cut at intervals. Parkinsonian tremor was rather more obvious during the first six months that he was on thyroid treatment.
The hair of the body may become scanty and lose its tendency to curl. Excessive growth of hair (hypertrichosis) in women after the menopause is an indication of disordered endocrine balance (loss of ovarian internal secretion?) and is only so far an accompaniment of age; it may be seen in comparatively young women from various causes.
The nails are often longitudinally ridged, brittle, hard, and thickened; but onychogryphosis is rather the result of neglect or of disease than solely of old age.
The brain as a natural result of atrophy becomes lighter; Boyd’s[147] tables show that the male brain is 3 oz., and the female brain 4 oz., lighter in persons over 80 years of age than in the decade 20 to 30. The convolutions, therefore, become separated and the amount of cerebrospinal fluid greater. The atrophy is not uniform, being less in the posterior third than in the anterior two-thirds. The nerve cells become smaller, pigmented, and degenerate. The brain is said by Cerlette to be affected by a process special to old age—miliary necroses scattered over the cortex and associated with changes in the small arteries which show remarkable knots; a condition which suggests a pathological softening secondary to arteriosclerosis, especially as the change does not come on constantly at a definite age period. Cavities with thickened walls, possibly due to miliary haemorrhages, or to softening around the vessels are also described. Metchnikoff’s description of phagocytic destruction of the nerve cells by macrophages has been seriously questioned and thought to be based on erroneous observation, the glia cells being regarded as macrophages (Marinesco).
The spinal cord shows an increased number of amyloid bodies, some diffuse sclerosis, often obliteration, by epithelial proliferation, of the central canal, and atrophy with pigmentation of the nerve cells, especially in the anterior cornua. The membranes may contain small calcareous plaques.
The arcus senilis, due to infiltration with fats, especially cholesterol and lipochrome, and to degeneration of elastic tissue at the periphery of the cornea, is often associated with arteriosclerosis (Monauni[148]). It is not a necessary accompaniment of age; among 321 persons over 80 years of age, it was absent in 114, or 35·5 per cent (Humphry); and it is well known that like grey hair, it may occur in those young in years. Nascher,[149] the author of Geriatrics, had an arcus senilis as a schoolboy. Rigidity and flattening of the crystalline lens lead to presbyopia, which may be premature and due to toxaemia, among the causes of which Ernest Clarke[150] gives intestinal toxaemia a high place. The power of accommodation is also impaired by weakness of the ciliary muscle brought about in the same way.
Skeleton.—The atrophy characteristic of senescence is well shown in the fixed tissues of the bony skeleton. Though the bones do not as a rule alter materially in size or shape, they do so markedly in substance from rarefaction and absorption, the latter taking place mainly from the inside of the bones and especially the cancellous tissue, the medullary cavity and the Haversian canals becoming larger (senile osteoporosis). Hence fractures near the joints, particularly intracapsular fracture of the neck of the femur, are favoured. The absorption of the alveolar border of the jaw is intimately connected with the loss of the teeth, and brings the mental foramen to the top of the edentulous mandible. The angle of the jaw at the junction of the body and the ramus now opens out and comes to resemble that of an infant. It is often stated that the angle of junction of the neck and shaft of the femur becomes less, more of a right angle, but Humphry regarded this as exceptional.
From muscular weakness the back becomes bent and as a result the vertebrae become altered in shape. Ossification of the anterior common spinous ligament—a change analogous to rheumatoid osteophytes around the more movable joints—is an added and not uncommon change but, like calcification of the costal and laryngeal cartilages, it is a morbid process, and when advanced constitutes spondylitis deformans. The intervertebral discs undergo some loss of elasticity and atrophy, thus contributing to the loss of height. The cranial bones are usually thinned, and the parietal bones may show symmetrical or nearly symmetrical oval areas of excessive absorption of the outer and even of the inner table, so that the epicranium and the dura mater may be in contact. These areas which are close to the longitudinal fissure must not in the case of ancient skulls be mistaken for examples of early trephining. The bony sutures tend to become obliterated. Instead of thinning and loss of weight the skull, especially the vault, may show thickening and be heavier than normal—a change involving chiefly the inner surface and ascribed by Sir George Humphry to shrinkage of the brain.
Calcification of the costal and laryngeal cartilages, which have a yellow tint from fatty change, is, like a similar change in the arteries, pathological and not part of the process of senescence. Thus among 10 recorded necropsies on centenarians the costal cartilages were calcified in 2 only. Calcification of the costal cartilages interferes with the respiratory movements and was regarded by Sir George Humphry, who tested for it by estimating the elasticity perceived when gentle pressure is exerted on the lower part of the sternum, as a bad omen for the future.
The teeth are usually, but not invariably, few in the aged, for care or lack of it, the accumulated effect of long-continued mechanical injuries, altered calcium metabolism, and diminished resistance to infection will necessarily influence the amount of decay. Statistics, especially Humphry’s, show that in extreme old age very few teeth are present, and it is tempting to correlate the diminished provision for mastication with the lessened need for food. Sir Isaac Newton, however, at the age of 85 was said to have lost one tooth only. The numerous reputed instances of a third dentition can be explained only by the appearance of a previously buried tooth through the atrophying gums, for a genuine third dentition would necessitate the presence of dental germs which do not exist.
The gastro-intestinal tract shows atrophy of the muscular coat and its secreting glands, so that dilatation of the thin-walled, pale stomach and colon occur on less provocation than in adult life and digestion is impaired; from lack of mucous secretion combined with loss of motor vigour constipation is common. It may be added that hypertrophy of the prostate by interfering with peristalsis of the colon has been thought to cause gerontal constipation (Hollis[151]). The pancreas shows fibrotic atrophy and becomes smaller and harder. From the loss of fat and muscular atrophy visceroptosis is not uncommon.
The liver diminishes in size and weight by about one half; atrophy of considerable areas may expose the vessels and ducts on the surface of the organ. Boyd’s tables show a difference of 18 oz. between the weights in persons in the decade 20–30 and in those over 80. Microscopically atrophy of the lobules and of the cells in the centres of the lobules have been described (Luciani[152]), but the latter change is not constant, for in a woman of 93 Salimbeni and Gery[153] definitely noted that the cells were not atrophied. That such atrophy of the liver cells is pathological is perhaps supported by D. Symmers’s[154] observation that in the pancreas of such cases the islands of Langerhans may show moderate enlargement, as if to compensate for failure of the glycogenic function of the liver. Pigmentation of the cells by a lipochrome is excessive, and the name brown atrophy has been applied to the condition which is seen in the other viscera of the old.
The lungs become smaller, lighter, and the elastic tissue degenerates; this is atrophous emphysema, and the chest capacity diminishes. Roussy and Leroux[155] found that these lungs commonly show endarteritis obliterans and fibrosis, conditions which favour infarction, infection, and the terminal bronchopneumonia to which the aged are so prone.
The voluntary muscles, according to Durante,[156] contain many fibres with large globules of fat; but Jewesbury and Topley,[157] who describe coarse fat globules mingled with brown pigment in the immediate neighbourhood of the muscle nuclei in 50 per cent of cases of various kinds, and almost constantly in old subjects, regard this condition as independent of true fatty degeneration, and are doubtful if it has any pathological significance. Excessive fatty and fibrotic change is found in cases of senile paraplegia without any lesion in the spinal cord or brain.
Heart.—Some difference of opinion exists as to the condition of the heart; Parkes Weber[158] says that the only true senile change is diminution in size and weight; this as it is worded is no doubt correct; but pure atrophy is less rare in the heart than in most parts of the senile body. Charcot[159] indeed stated that it does not atrophy in old age, but preserves the dimensions of middle life. The heart may even hypertrophy in old people; this is pathological; Councilman[160] found it in 248, or 43 per cent, of 580 persons over 60 years of age, and could not refer it to aortic or renal arteriosclerosis or to the diminished capillary area in the skin; but the average blood pressure 158 systolic/88 diastolic of the cases with cardiac hypertrophy was higher than that 130/78 of the others.
Fatty degeneration of the myocardium is very frequent; Charcot stated that at the Salpêtrière it was almost constant in old women, but according to Councilman there is no clear evidence that it produces permanent injury or functional insufficiency; he noted some fibrosis in 15 per cent of his cases. Atrophy of the epicardial fat—serous atrophy—is common, and increase of the so-called lipochrome pigment in the muscular fibres which become smaller and fewer—brown atrophy—is frequent as it is in the other organs in old age.
Chronic valvulitis and subendocardial fibrosis are, like arteriosclerosis, common morbid changes.
Arteriosclerosis, contrary to what has been stated by Huchard and others, is not constant in a considerable degree in old people, and therefore cannot, as Demange and others considered, be regarded as the cause of the atrophic changes seen in old age. Arteriosclerosis is due to several factors, namely, infection and intoxication of various kinds and to damage caused by long-continued high arterial blood pressure. The primary changes are degeneration and weakness, however brought about, in the middle coat. Ophülz[161] has recently discussed the question whether the degeneration is entirely or largely a senile change; if it were so, the curve of the incidence of arterial sclerosis would begin gradually about the age of 40 years, so as to include premature cases, and rise slowly until the age of 55 years, when there would be a sudden increase to 80 or 90 per cent, and at the age of 70 it would be improbable that any one would be free from well-marked arteriosclerosis. He found that the curve of incidence was very different from this; beginning much earlier its rise is gradual all the way without any sudden increase, and indeed seems, if anything, to be retarded by old age. Old persons may have practically healthy arteries, so, although arteriosclerosis may undoubtedly produce atrophy and senile changes in the tissues and organs by diminishing the blood supply, for example in the case of the red granular kidney, it cannot be regarded as the causal factor in healthy old age.
The primary calcification of the middle coat, sometimes called Mönckeberg’s sclerosis, which leads to the formation of regular rings in the degenerated muscular media and the “pipe-stem” arteries associated with senile gangrene, may be independent of, or combined with, endarterial sclerosis. It follows fatty degeneration of the media, which is the commonest form of medial degeneration in the aged, and specially picks out the elastic fibres.[162] The femoral, tibial, radial arteries and the aorta are most often affected. It is difficult to estimate its incidence, but that it is not very common, at any rate in a high degree, seems probable from the comparative infrequency of its detection in x-ray examinations of the lower limbs in old people. It would be natural to associate its occurrence with the rarefaction of bone that goes on in advanced life, and so to consider it as in some respects different from the secondary calcification in endarteritic sclerosis; in answer to an enquiry Professor W. T. Councilman of Harvard kindly wrote to me that he did not regard calcification as characteristic of any particular type of arterial disease, lime salts being in certain cases more easily deposited in any pre-existing lesions. Klotz describes fatty and calcareous change in the middle third of the media of the aorta as quite characteristic of senescence.
Cazalis’s famous aphorism “man is as old as his arteries” is true in so far that the state of the arteries is a good index of the general condition, for they are extremely prone to suffer as the result of infection, toxaemia, and strain; strictly speaking, therefore, the state of the arteries is not so much an index of the individual’s age as of his adventures.
Phlebosclerosis, analogous to arteriosclerosis, is common, and dilatation, often due to stagnation and lack of the normal vis a tergo, of the veins is a familiar change in the aged.
The capillary area is diminished in the skin and elsewhere, but not uncommonly there are dilated venules or angiomas on the skin; the latter, commoner on the trunk and upper limbs and in men, were formerly known as “de Morgan’s spots” and were thought to accompany cancer, but the association is only due to a rough correspondence of their age incidence.
The blood of healthy octogenarians may not show any departure from that of the earlier periods of life as regards the number of the reds and the amount of haemoglobin (Hansen[163]), though some have described a secondary anaemia. Thus in a female centenarian Macnaughton[164] found slight secondary anaemia with a normal number of leucocytes, the differential count showing a relative lymphocytosis. The red bone marrow diminishes, its place being taken by fat cells.
The lymphoid tissues undergo atrophy all over the body including the leucoblastic bone marrow, but though it does not appear that the blood shows any definite change in the leucocyte count it is tempting to correlate the diminution of resistance to acute infections, such as pneumonia and erysipelas, with the atrophy of the lymphoid tissue. The alimentary canal often shows lymphoid atrophy in a high degree, but two normal Peyer’s patches were present in a man reputed to be 106 years old (G. Rolleston[165]).
The spleen, in common with the lymphoid tissues elsewhere, shows atrophy, sometimes to an extreme degree, so that instead of the normal weight of 7 oz. it weighs a few drams only. The capsule is thrown into folds, and is somewhat opaque; from atrophy of the pulp and Malpighian corpuscles the vessels and fibrous trabeculae become prominent. The thymus, contrary to the general opinion that it undergoes involution long before puberty, has been found by Hammar[166] to increase in size up to puberty when involution begins, but proceeds so gradually that even in old age it is functional.
The thyroid, unless there is cystic change, is smaller than natural; thus out of 40 thyroid glands from individuals between the ages of six months and 77 years the smallest was in a woman aged 77 (Hale-White[167]). In colour it is darkish brown and on section rather dry. Dr. Donaldson, Lecturer on Pathology at St. George’s Hospital, has specially examined 19 thyroid glands from patients between the ages of 57 and 93; of these five showed cystic change; they all showed increase in the amount of fibrous tissue which was progressive with age, and in the absence of cystic change the size of the vesicles and amount of colloid material were diminished.
The Parathyroids.—From examination of a number of specimens Dr. Donaldson finds that in old people the parathyroids appear to be free from retrogressive changes, but he cautiously requires further experience before concluding that this is the rule.
The adrenals show involutionary atrophy in common with the body as a whole, but sometimes the cortex is enlarged from excess of lipoids, usually associated with considerable atheroma, and may also show adenomas. As the increase in size of the adrenals is cortical its relation to high blood pressure, if any, is that of a remote result, namely from arteriosclerosis, and not causal as has been suggested. According to G. M. Findlay[168] the amount of lipochrome in the cells of the adrenals increases with advancing years and is accompanied by the appearance of melanin in their nuclei.
The kidneys show definite atrophy, and Councilman,[169] who has recently made a study of them in 580 persons over 60 years of age, calls the condition chronic atrophic nephropathy. The fat in the renal pelvis is more obvious than usual, the capsules are slightly thickened and occasionally but by no means always adherent, the surface finely rough and sometimes showing small cysts, but the large and irregular depressions characteristic of a granular kidney are not common. There are, however, areas of fibrosis, and the cortex and medulla are equally atrophied. Microscopically some glomeruli are fibroid, others smaller than natural. In three-fourths of his cases the renal vessels showed arteriosclerosis due to primary atrophy of the media with compensatory hypertrophy of the intima; but Councilman gives reasons for hesitation in accepting the obvious conclusion that the senile kidney is the result of the vascular change.
The prostate shows some degrees of enlargement after the age of fifty in the vast majority of men, but in only a percentage of these are there symptoms referable to it. Kenneth Walker[170] finds that the maximum size is reached at the age of 60 and that from then onwards there is a slow diminution in size; among 340 men between 80 and 90 there were 11, or 3·2 per cent, and among 92 men between 90 and 100 one only with hypertrophy of the prostate (Humphry). The causation of prostatic hypertrophy has been much discussed; that its association with arteriosclerosis (Launois[171]) is anything more than a coincidence, the two conditions being common in the later years of life, seems improbable; Walker found the two associated in 10 per cent, and he regards the change as part of a general enlargement and thickening of the peri-urethral, sub-cervical, and sub-trigonal glands, and, as the interstitial cells in the testes become fewer and degenerated, he considers that the prostatic enlargement is possibly a degeneration connected with a disturbance of the endocrine balance. Nemenow[172] argued that prostatic enlargement was due to proliferation of the interstitial cells following senile atrophy of the seminal tubules of the testes, but K. Walker found that in prostatic enlargement the interstitial cells are diminished rather than increased in number. An interesting parallel has been drawn between the involutionary changes in the mamma and the prostate, and it is probable that the same underlying factor is at work in both (Walker, Paul). Hertoghe[173] regarded some cases of prostatic hypertrophy as due to senile dysthyroidism, and recently benefit has been reported from thyroid medication and also from prostatic extract. Dr. Leonard Williams has told me of cases, as yet unpublished, showing well-marked relief of symptoms and diminution in the size of prostatic enlargement after doses of thyroid extract (½ grain once) and colloidal iodine (one dram three times) daily. The prostatic plexus of veins is often enlarged and may contain phleboliths.
The testes become smaller, softer, and commonly show some atrophy of the tubules with disappearance of the epithelial lining and thickening of the basement membrane; but the testes of old men may be free from any such change and the spermatozoa in the vesiculae seminales may be active. According to K. Walker the interstitial cells gradually diminish in number from the age of 30, but they may be present in men over 80, and Mott[174] remarks that their persistence may account for an increased and perverted sexual appetite, due to stimulation of the desire without the power to perform the sexual act.
The penis becomes smaller, often retracted, the glans harder, and the scrotum smaller.
The ovaries become shrivelled and fibrotic; the ova disappear or small cysts may form. It is difficult to find statements about the presence or absence of interstitial cells in the senile ovary. Professor Turnbull has kindly informed me that in old women an occasional cell which might be, but is not certainly, an interstitial cell is visible, and that if they are interstitial cells their number must be small and their development poor.
The uterus becomes small, its cavity round, and the cervical canal may be obliterated. The external genitals atrophy.
The mamma in women shows involution changes and when excessive (cystic disease) these may, as Paul[175] has pointed out, be compared with prostatic enlargement in the male.
VII
PHYSIOLOGY OF OLD AGE
The basis of the physiology of old age is progressive diminution in functional activity, which corresponds to the characteristic structural atrophy of the organs and tissues. Thus the lowered functional activity of its glands is manifest in the dry skin; according to Haneborg[176] there is usually a fall in the percentage of hydrochloric acid in the gastric juice, though Bell[177] disputes this. The lessened amount of mucus from the intestine probably plays some part in the tendency to constipation. Other evidences of lowered metabolic rate are seen in the diminished efficiency of the acid-base equilibrium (MacNider[178]) and the increased degree of urea-nitrogen in the blood, as shown in 50 per cent of 41 persons between 70 and 88 years of age examined by Rappleye.[179]
Temperature.—Before the era of the clinical thermometer it was supposed that the body temperature of the aged was below normal. This belief was part of the ancient view that the cause of old age was exhaustion by the natural heat of the radical moisture which, like lamp oil, supported the innate heat and with the passage of years could not be supplied as perfectly as before; as a result of this loss of radical moisture the body was thought gradually to dry and cool.[180] But it is now known that the internal temperature is almost constant at all ages, and Charcot proved that the only real difference is that the axillary is lower than the rectal reading; this is due to the diminished vascularity of the skin and to the corresponding fall in the loss of heat, which again may be correlated with the lower metabolic rate of old age. Aub and Dubois’[181] observations on six men between 77 and 83 years of age, mainly with arteriosclerosis, granular kidney, and emphysema, showed that the basal metabolism was 12 per cent below the average for men between 20 and 50.
Blunting of sensibility to pain is a beneficent process, suggesting that with the gradual process of involution and approach to a physiological death the need for the warning normally conveyed by symptoms is no longer needed. This is connected with the simultaneous atrophy of the nervous tissues which look after the conduction, perception, and reference of pain. The latency of disease, as shown by an absence of the characteristic symptoms observed in earlier adult life, is often remarkable in the aged. Thus death may occur suddenly from extensive but entirely unsuspected pneumonia; the passage of biliary or urinary calculi may be unaccompanied by the violent colic of these events in ordinary cases, and extensive malignant disease may exist without any definite localizing discomfort. This failure in the power to react is also shown in fevers and infections (vide p. 142).
Cutaneous sensation is little affected, and indeed the aged are very sensitive to cold. Taste and smell are impaired, and presbyopia is due to changes in the crystalline lens. The pupils are contracted and the iris sluggish. From weakness of the orbicularis palpebrarum muscle ectropion and epiphora may noticeably change the facial appearance. With advancing years hearing commonly becomes less acute from various causes, and after 60 there is a successive decrease in the number of persons with normal hearing. According to Albert Gray[182] there is probably a characteristic form of deafness for the higher notes of Galton’s whistle in all old people, even when for all practical purposes there is no obvious defect or tinnitus; this he regards as due to progressive atrophy of the ligamentum spirale. Chronic progressive labyrinthine deafness, due to atrophy of the auditory nerve and fibrosis of the ductus cochleariae, is the most common condition in persons over 60. Fixation of the stapes frequently causes deafness, and the sequels of middle-ear disease accumulate with advancing years. Gouty eczema of the external auditory meatus and collections of wax may seriously interfere with hearing. Tinnitus in the elderly is commonly associated with high blood pressure and arteriosclerosis.
Appetite for food is sometimes capricious; old people may eat excessively, possibly because the pleasures of the table are the only ones to which they feel equal.
Muscular movement is slow and somewhat uncertain, and the reflexes are diminished except in the presence of sclerosis of the spinal cord. According to Moebius the knee-jerk is often absent in normal old persons, but Sternberg, by employing methods of reinforcement not available in Moebius’ time, found that it was invariably present even in the tenth decade.
The sleep of the aged is less continuous, and from interruptions often appears to them to be much less than it really is. There is often a tendency to irregularity, bad and good nights alternating. But too much attention to disturbed sleep in the aged must be avoided, as hypnotics are inadvisable, and it has been urged by Sir Hermann Weber and others that too much sleep is more harmful than too little.
In old age the mental condition varies in different individuals according to their previous character and their present physical state. Freedom from sexual and other perturbations often renders the minds of old people calm, tolerant, less susceptible to disappointed ambition, and philosophic when the part of spectator has been accepted in place of that of actor in life’s drama. In what may be regarded as normal old age psychical activity diminishes; not only do initiative, elasticity, and originality fail, but new ideas and fresh lines of thought are assimilated with difficulty; hence the old are commonly conservative and laudatores temporis acti. Mental fatigue occurs more readily and the power of concentration and attention is impaired so that the old may appear deaf; the mind begins to show disintegration and a return to the primitive condition in which each act demands individual care; it has indeed been said that old age is nothing but progressive fatigue. A less agile memory for names is commonly one of the early symptoms of senescence, and long precedes the characteristic loss of memory for recent events while that for the remote past remains, as if the nerve cells were photographic plates which in course of time have all become occupied with impressions. With commencing failure of memory there is often a tendency to make the same remark or tell the same story repeatedly, to mislay things, and unconsciously to become careless about personal appearance and habits. As a kind of protest against the inevitable there may, in the early stage of old age, be a tendency to ape the young and to conceal the true age; thus a man may remove the date of his birth from Who’s Who and books of reference, and a mother may delay the “coming-out” of her daughter. On the other hand, at a later stage there may be the opposite desire to appear a wonderful prodigy of senescence. The old are notoriously less subject to feel the loss of relatives and friends by death; they become more self-centred; this may be because retirement from active work switches their minds on to their own feelings, and possibly in part depends on loss of touch with the external world, resulting from failure of the sense organs. This when exaggerated develops into selfish dependence and demands on relatives. Senile vanity is not uncommon, and Eden Phillpotts[183] remarks that all old people love to be in the centre of the stage, one of the pathetic things in life being that they are seldom allowed to be there. The ego-centric frame of mind may lead to hypochondriasis with fads and meticulous attention to details of personal health and to experiments in diet and patent medicines. Loss of control, due to failure of the higher centres, engenders restlessness, garrulity, emotional weakness, and peevishness. There may be considerable variation in the moods, so that the deep depression of one day may vanish the next, and irritability and apathy may alternate.
Regression, which closely corresponds to the “devolution” of Hughlings Jackson, who argued that in disease the organism tends to retrace the steps of its development, accounts for the phenomena of “the second childhood.” Thus the old are prone to nervous apprehension, and liable to suggestion and to hysteria which Rivers[184] defined as a protective mechanism representing a recrudescence of the reaction to danger in an early stage of animal development. Will power, like their gait, becomes hesitant and uncertain. This devolutionary change progresses partially and not universally; memory for personal names, as mentioned above, is often the first to fail, because, like the mathematical faculty, it has from the attendant difficulty a high place in the order of mental processes; hence forgetfulness of personal names is a criterion of psychical fatigue and neurasthenia (Dupuis[185]).
In old animals it is natural for the instinct of self-preservation to fade, as is exemplified in the day-flies which in their larval stage are well endowed with this property, and as their end draws near animals seem to acquire an instinct for death comparable to that for sleep. But in human beings, although they usually dislike old age, there is generally what Matthew Arnold[186] called “a passionate, absorbing, almost bloodthirsty clinging to life.” Metchnikoff specially investigated this point and found hardly any instances in which death was anticipated with the same feelings of pleasure as is sleep by the weary. Considering the discomforts of many old people it is rather remarkable how very seldom they endorse the words of the burial service: “We give thee hearty thanks for that it hath pleased thee to deliver this our brother out of the miseries of this sinful world.” Various explanations have been offered for this want of harmony between the mental and physical states of the old; it has been ascribed to the idea of eternal punishment, and to the presence of pathological conditions which bring on senility and death prematurely and thus alter what should be the normal mental attitude of healthy old age. In speaking of the usual fear of death in old people it should be mentioned that shortly before death this commonly disappears and, as G. E. Day,[187] R. W. Mackenna,[188] and Thompson and Todd point out, the aged when seriously ill commonly regard death as a welcome release; the famous William Hunter’s last words in his sixty-fifth year expressed his sense of resignation: “If I had strength enough to hold a pen, I would write how easy and pleasant a thing it is to die.”
The Cardio-Vascular System.—The pulse rate is usually rather increased in frequency as compared with that in adult life; extra-systoles are so common in persons who appear otherwise normal that they cannot be regarded as having any important significance. Among Sir George Humphry’s collection of 824 persons over 80 years of age one-fifth had an irregular or intermittent pulse.
Although, like arteriosclerosis, a well-marked high blood pressure without evidence of renal disease, to which Sir Clifford Allbutt has given the name of senile plethora or hyperpiesia, is common in the decline of life, it is a pathological and not a physiological change; and a distinction must be drawn between the gradually rising blood pressure seen from birth onwards and an increase above that normal to an arterio-vascular system that has been active for over half a century. In the same way the venous pressure increases with age (Hooker[189]). That a definitely high blood pressure in the aged is pathological appears to be shown by observations quoted by Councilman from the Peter Bent Brigham Hospital, Boston; among 94 patients (male and female) averaging 66 years of age, 44 per cent with cardiac hypertrophy as shown by necropsy, had an average blood pressure of 158 systolic / 88 diastolic, whereas the 56 per cent without cardiac hypertrophy had an average blood pressure of 130/78. In both series the differences between males and females were never more than 7 mm. Hg. From observation of 102 Chelsea pensioners over 75 years of age Thompson and Todd found that the average blood pressure was 145 systolic / 80 diastolic, estimations varying from 190/100 to 115/70, and that the average pulse pressure, or difference between the systolic and diastolic pressures, was 67 mm. They came to the conclusion that it was not possible to arrive at a normal blood pressure for old people on account of the varying conditions of the heart and arteries.[190]
The urine, in consequence of the lowered metabolism and general atrophy, is somewhat diminished in quantity with a fall in the solids, though the specific gravity remains about normal. The chlorides are stated to be normal and the phosphates and urea to be diminished. Slight glycosuria as a result of a low sugar tolerance (vide Spence[191]) is not uncommon, especially in obesity. Prolonged confinement to bed has been thought to be responsible for casts in the urine. A trace of albumin is not rare; this may be due to various factors, and in itself is not a cause for anxiety; but a well-marked fall in the specific gravity is a sign of renal inadequacy which may be preceded and anticipated by the discovery of nitrogen retention in the blood.
Sexual activity in man wanes generally speaking after 50, but there are great variations in this respect, and sometimes there are periods of considerable excitement in old men, often thought to be associated with prostatic enlargement.
It would naturally be expected that wounds and fractures of bones would heal more slowly in the old than in the young, and, according to Carrel and Ebeling,[192] the cicatrization of human wounds varies inversely, if accurately measured, with the age of the patient; Humphry, however, found that, provided sloughing did not occur, wounds and ulcers in the aged heal as quickly as in middle life, and that the failure of union in intracapsular fracture of the neck of the femur is due to want of apposition and not to the age of the patient.
In some respects the reaction to drugs in the senescent body is different from that in ordinary adult life. In old people absorption from the alimentary canal is slow and this is particularly so with gelatin-coated pills and drugs, such as cinchona, containing tannin, which should therefore be avoided. The physiological response to drugs is slower and more prolonged than in early life, so that for this reason and from the frequency of constipation an accumulated action is thought to be more likely to occur in the aged. It is sometimes said that large doses are not borne well by the old and that morphine is dangerous as it is in infants, but Nascher[193] states that if, in order to obviate the paralysing effect of morphine on a weakened respiratory centre, atropine is given before the morphine so that their action can be timed to coincide, instead of giving them at the same time when the effect of the atropine comes later, morphine can be given in the same doses as in maturity. Purgatives may be required in larger doses than in ordinary practice. According to Leonard Williams[194] bromides are likely to produce mental confusion in old people and if persisted in, even in ordinary doses, may be followed by vascular thrombosis and permanent impairment of the intellectual powers. Sedatives and hypnotics when necessary should be given in small doses and discontinued as soon as possible; but they may be necessary for restlessness which would otherwise seriously exhaust the failing strength.
VIII
THE DESCRIPTION OF OLD AGE IN THE TWELFTH CHAPTER OF ECCLESIASTES
When first approaching the subject of old age every one must recall the famous description in the first six verses of the twelfth chapter of Ecclesiastes beginning “Remember now thy Creator in the days of thy youth while the evil days come not, nor the years draw nigh when thou shalt say I have no pleasure in them.” Formerly ascribed to King Solomon (977 B.C.) the book of Ecclesiastes (in Hebrew Koheleth = the preacher) has been shown by the higher criticism to date only from the end of the third century B.C., and from internal evidence, namely references to the brain, spinal cord, and other anatomical structures, though expressed with poetic imagery, it may fairly be assumed that a medical man was concerned with its construction. In his attractive work, A Gentle Cynic,[195] the late Professor Morris Jastrow, jun., of Philadelphia explained that the book of Ecclesiastes as it appears in the authorized version, consists of (i.) the original, cynical, but good-natured obiter dicta of the unknown dilettante who preferred to veil his identity under the name of Koheleth, and (ii.) additions and modifications made by various hands to render it more orthodox and compatible with the tradition that it was written by Solomon; thus the admonition “of making books there is no end and much study is a weariness of the flesh” may very probably have been intended as a hint that Koheleth’s views should not be taken too seriously. Following this conception Jastrow reconstructed the text of the book of Ecclesiastes to what he argued was its original form, and compared it with the more modern writings of Omar Kháyyám and Heinrich Heine. As we all must have speculated over the correct interpretation of the various metaphors in this description of the last stage of life, the explanations offered by others, such as Andreas Laurentius (1599),[196] Master Peter Lowe (1612),[197] founder of the Faculty of Physicians and Surgeons of Glasgow, Bishop J. Hall (1633),[198] John Smith (1665),[199] Richard Mead (1775),[200] and Jastrow may be very briefly mentioned. The second verse, “While the sun, or the light, or the moon, or the stars, be not darkened, nor the clouds return after the rain,” is regarded by Laurentius, Lowe, and Hall as referring to the ocular disabilities of old age, whereas Smith and Mead consider that mental failure and depression are meant. As regards the third verse, “In the day when the keepers of the house (the hands) shall tremble, and the strong men (the legs) shall bow themselves (become bent), and the grinders (teeth) cease because they are few, and those that look out of the windows (the eyes) be darkened,” there is general agreement, Lowe specially designating cataract as meant in the last sentence. “And the doors shall be shut in the streets,” is regarded as referring to the mouth by Laurentius and Mead, and to the various orifices including the results—constipation and dysuria—by Smith; “when the sound of the grinding is low,” is considered by Jastrow to mean impaired hearing, and by Smith as a lowered rate of metabolic processes, such as assimilation, blood formation, and various secretions. “And he shall rise up at the voice of the bird,” implies, according to Smith and Mead, the early waking of the elderly; “and all the daughters of music shall be brought low” signifies to Laurentius the failure of voice, to Mead deafness, and to Smith all the organs concerned with sounds, namely the lips, tongue, larynx, and the auditory apparatus. “Also when they shall be afraid of that which is high, and fears shall be in the way” is regarded by Smith as describing the general mental attitude of anxiety for things both small and great and a bad head for height, but a more modern commentator suggests that “afraid of that which is high” refers to dyspnoea on climbing a hill. “And the almond tree shall flourish” is by Laurentius, Hall, and Smith thought to refer to the white hair or “churchyard flowers” of the old, but Mead argued that loss of smell is meant. “And the grasshopper shall be a burden” has been very variously interpreted: Hall is content to accept the literal meaning that the least weight is a nuisance; Laurentius and Lowe understand oedema of the legs; John Smith that the aged body undergoes the reverse change of shrivelling, hardening, and angularity; Mead suggests scrotal hernia, and Jastrow, as according to the Talmud the grasshopper is a symbol for the male sexual organ, considers that the sentence refers to the loss of sexual activity. In the sixth verse the words “Or ever the silver cord be loosed,” refers, according to Laurentius, Lowe, Mead, and Jastrow, to kyphosis, but Smith translates them into paralysis of the spinal cord and nerves. “Or the golden bowl be broken,” signifies cardiac failure to Laurentius and Lowe, but cerebral haemorrhage to Smith, who thus explains the next line, “or the pitcher (the veins) be broken at the fountain (the right ventricle), or the wheel (the arterial circulation) broken at the cistern” (the left ventricle), and therefore concludes that King Solomon was perfectly acquainted with the circulation of the blood discovered by William Harvey in 1616. “The pitcher” is regarded as the vena cava by Laurentius, and as the urinary bladder by Mead and Jastrow; “the wheel broken at the cistern” suggests the kidneys and bladder to Laurentius and Lowe, cardiac failure to Mead, and intestinal and hepatic insufficiency to Jastrow.
IX
DISTINCTION BETWEEN HEALTHY AND MORBID OLD AGE
In any individual instance the exact line which separates healthy old age (senescence) from old age complicated by a morbid process, i.e. by some factor other than the gradual atrophy and restriction of functional activity, or senility, may be difficult or impossible to draw. The dictum of Terence, Cicero, and Sanatorius that old age is a disease probably still finds acceptance with many. It is indeed clear that exposures to infections and poisons would produce changes more easily in cells that are beginning to fail in vitality. Healthy old age should be a normal process of involution with progressive atrophy and loss of vitality, and free from any morbid change due to other factors whether extrinsic, such as infection, or intrinsic and due to abnormal metabolism. As the bodies of the aged usually show a number of changes additional to those of normal involution, some of which, such as arteriosclerosis, are so frequent that they have sometimes been erroneously regarded as part or even the cause of old age, it is essential to recognize and to try to draw a distinction between physiological old age and senility from the effects of disease (Senium ex morbo). But about the anatomy and physiology of normal old age much remains to be learnt; more indeed is known about the pathology of the aged, a subject which includes the damage done in the past, perhaps in youth, and morbid processes starting during advanced life.
In attempting to decide when old age should be regarded as a disease or merely as a process of involution or retrogression which naturally follows the earlier and progressive stage (youth) of development, it may be well to refer to the meaning of “disease” and “health.” Disease, or want of ease, has been variously defined as evidence of imperfect function, as discord, and as maladjustment between the individual and his environment (Moon[201]), and Health as the indication of perfect functional activity, as harmony between the individual and his environment. In the different stages of life’s cycle there should be a correspondence between the individual’s desires and his powers so that there is harmonious co-ordination; this should hold good in normal old age as it does in youth.
The frequent complaints of old people show that there is maladjustment and disease, for if the decline of vitality were uniform throughout the body the equilibrium would, though altered as a whole, still be maintained, and there would no longer be a discordant desire for activity, for which other parts of the body are, from a more advanced state of atrophy or morbid change, unable. Thus it would appear that the conscious disabilities of old age are not the necessary results of a true physiological involution, and that the late Sir Andrew Clark’s definition of Old Age as “the period at which a man ceases to adjust himself to his environment” should be regarded as true of senility or morbid old age but not of senescence or healthy old age.
The organs of the body do not all start to grow old at the same time or progress at the same time. That such variations in involution may be so exaggerated as to become morbid without any very obvious cause is highly probable, but the latter event is clearly a departure from the progress of normal old age. The precocious atrophy of some tissues or organs may be ascribed to several factors, such as inherent weakness, the effects of overstrain, though without producing gross changes, or to the influence of a definite infection or intoxication in the past. Thus deafness may be hereditary, senile paraplegia has been known to occur in energetic walkers, and thyroid deficiency may be the outcome of a past attack of enteric fever. These errors in the chronometry of life, as Sir James Paget[202] termed the different ageing of organs, cannot be regarded as a physiological process.
X
DISEASES IN AND OF OLD AGE
Strictly speaking, it cannot be said that there are any diseases special to length of days, for premature senility shows the changes and diseases usually correlated with ordinary old age. Inherent want of vitality and the resulting degenerative atrophy, or Gowers’s abiotrophy, may imitate the results of prolonged wear and tear of the tissues, and thus it appears that Charcot’s[203] group of diseases special to old age, namely senile marasmus, senile osteomalacia, senile atrophy of the brain, senile heart weakness, and arteriosclerosis, are not confined to senescence. Old age, however, is prone to the incidence of diseases which are chiefly but not exclusively seen in the evening of life, such as those due to the degenerative changes resulting from the accumulated effect of past infections and from metabolic disturbance. Thus arteriosclerosis, granular kidney, cardiac failure, cerebral haemorrhage, emphysema, hepatic cirrhosis, prostatic enlargement, and carcinoma commonly appear in the sixth decade. In a series of five publications dealing with the diseases of the age of fifty, which he calls the critical age, Leclercq[204] describes, in addition to some of the above, gout and paragouty affections, obesity, diabetes, cardio-aortic diseases, and albuminuria. Old age, moreover, modifies the manifestations and course of infections, notably of pneumonia and erysipelas. It would be unnecessary and from reasons of space impossible to refer to all the diseases that may attack the aged, but a few remarks will be made about some disorders that appear to call for special notice.
Senescence has some nosological compensations; thus some acute infections, such as measles, scarlet fever, enteric fever, and diphtheria, are very rare, probably because immunity has gradually been developed in the course of time; pneumonia and erysipelas, however, are notable exceptions in being specially prone to occur in the aged. Migraine usually becomes less troublesome or disappears with the march of years. As mentioned on p. 86, malignant disease is comparatively rare in very advanced age; lymphadenoma and leukaemia are rarer than in early life; and as pathological, like normal, processes are slower, carcinoma, especially of the breast, may become stationary.
Diseases of the Skin.—From atrophy of the skin and its secretory glands the skin is less resistant to infection and accordingly has been thought to be more susceptible to parasitic attack, such as pityriasis versicolor. The aged who are often less scrupulous in cleanliness than their juniors are more prone to skin affections, such as eczema, erythema, and erysipelas. The so-called senile prurigo is largely due to the presence of lice. From the atrophic condition of the skin the cutaneous nerves are more exposed, and this has been regarded as playing a causal part in senile pruritus, which is an exception to the general rule that sensory impressions are less prominent in the aged than earlier in life. It may, like prurigo, be due to an external cause, such as pediculi, or it may be metabolic in origin. In almshouses and institutions for the aged epidemics of scratching may develop from imitation of a genuine case of pruritus. Senile pruritus is usually general and from its obstinate resistance to treatment may be a terrible affliction. Sir Gilbert Blane (1749–1834) suffered from it for the last 13 years of his life, and was obliged to take opium in increasing quantities until his daily dose reached the equivalent of a dram of the solid drug.
Erysipelas, like pneumonia, with which or with bronchopneumonia it may be combined, is less obvious in its symptoms than in ordinary adult life on account of the diminished power of reaction, as shown by the slight degree of leucocytosis in the aged in erysipelas (Lamy) and by its longer course. From want of resistance and arteriosclerosis, especially Mönckeberg’s form with calcification of the media, senile gangrene may follow slight accident or injury, such as occurs in cutting the toe nails. Absorption from the gangrenous area may cause toxic glycosuria, and such cases, when they come under observation at this stage, are sometimes regarded as diabetic gangrene. It is remarkable how well amputations for diabetic gangrene do; in July 1922 I saw with Professor F. H. Edgeworth a man with double amputation of the legs perfectly healed, and in good health though the glycosuria persisted.
Herpes zoster, though far from confined to advanced life, has in the old the unfortunate tendency to leave persistent pain in its site. Rodent ulcer, although sometimes seen comparatively early in life, is specially common in advanced years. It often supervenes on the dry yellow or brown spots (senile keratosis) seen on the face in persons over 60 years of age.
Vertigo is extremely common in later life and may be due to various causes; the most frequent form is that of aural origin, such as labyrinthine or nerve lesions and chronic changes in the middle ear. Increased blood pressure and cerebral arteriosclerosis are frequently responsible. Attacks of giddiness may occur in Stokes-Adams disease or follow exertion in the aged, as if from cerebral anaemia; and gastric disturbance may apparently also be a determining factor. In rare instances epilepsy or migraine may be represented or initiated by vertigo.
Senile tremor, rare under the age of 70, begins in the hands, especially in that most used, and spreads to the neck and head, rarely occurring in the lower limbs. It is a slow intention tremor, from 4 to 5 per second, and is distinguished by its relation to movement from that of paralysis agitans which is continuous but diminished on muscular contraction. The tremor of the jaw resembles that of munching food; that of the lips is fine. It is compatible with good health.
Paralysis agitans, described by James Parkinson, surgeon and palaeontologist, in 1817 as “the Shaking Palsy,” has now about a century later been shown, largely as a result of S. A. K. Wilson’s work, to be one of the forms of the extra-pyramidal symptom complex and due to degenerative changes in the efferent motor system of the globus pallidus system. Although juvenile forms occur and encephalitis lethargica may show the Parkinsonian syndrome, paralysis agitans is a disease of the early part of the later period of life, the great majority of the cases beginning between 50 and 70 (Gowers[205]), after which there is a small incidence only. It is twice as common in males as in females. Though unfortunately, from the degenerative nature of the lesion, incurable, it is a chronic disease; thus Maclachlan[206] refers to a Chelsea pensioner aged 107 years in whom it was known to have existed for 47 years.
Vascular lesions, haemorrhage or thrombosis, are the most important factors in the production of grave nervous disease between the ages of 50 and 70; among 500 cases of cerebral haemorrhage 321, or 64 per cent, and of 110 cases of cerebral thrombosis 67, or 61 per cent, occurred in the sixth and seventh decades (Michell Clarke[207]). Cerebral haemorrhage increases with frequency from the fourth decade and the largest number of cases occur between 50 and 60. From analysis of 154 cases at St. Bartholomew’s Hospital F. W. Andrewes[208] found that the apparent maximum is in the middle of the sixth decade, but that correction for the age distribution of the population shows that the liability of the individual to this form of death increases steadily up to old age. Thrombosis of atheromatous vessels is an accident of later incidence than cerebral haemorrhage, and thus contrasts with hemiplegia due to syphilitic endarteritis which occurs about the prime of life.
The physiological involution of the mind and accompanying organic changes in the brain gradually shade off into senile dementia. A regression to the mental state of childhood, which Dupré[209] called puerilism, may occur in widely different conditions, such as structural change of the brain, hysteria, and toxaemia. It may be acute and be transient or come on slowly and be permanent. Just as an old man may relapse into the speech and accent of his youth, so if he had a hard pecuniary struggle in his early days may he become miserly in the evening of his life.
Senile dementia is an exaggeration of the mental changes occurring in old age and due to further changes in the brain from vascular disease or toxic influences. It varies much in its features; some patients are maniacal, others depressed and melancholic, some feeble, some delusional, and a few immoral. The senile mania may be mainly nocturnal and was compared by Clouston[210] to the night delirium of a febrile neurotic child; it may pass into dementia. Of the melancholic group in which suicide may occur Clouston found that 30 per cent recovered.
Senile paraplegia may be divided into four etiological groups: (1) The functional dysbasias or pseudo-paraplegias described by Marie and Léri,[211] which in general terms resemble those met with during adult life, but the varieties are less distinct in the old. Quesnel[212] recognizes three groups of functional disturbance of walking in old people: (a) the slight and usually curable, (b) severe functional disturbance depending essentially on the mental state of the patient, and (c) the organo-functional in which a bony, articular, or nervous lesion is present; thus confinement to bed for a fracture may cause a functional paraplegia. (2) Spastic paraplegia due to sclerosis in the lateral and posterior columns of the spinal cord; the influence of arteriosclerosis, as advocated by Oppenheim, has been the subject of some debate, and Lejonne and Lhermitte point out that the nervous lesions are not necessarily perivascular and that there is a want of proportion between the vascular and the nervous changes. (3) Paraplegia of cerebral origin with descending degeneration in the cord and mental deterioration. (4) Paraplegia from muscular fibrosis and contracture, the central nervous system being intact.
From the presence of emphysema bronchitis is prone to occur in the old. Lobar pneumonia and bronchopneumonia. Lobar pneumonia has always been considered the great enemy of the aged; it is often latent, and may be found after sudden death and in persons supposed to have died of old age, because they were walking about or complained not at all or only of trivial symptoms. In spite of Charcot’s[213] considered opinion to the contrary, it is probable that pneumonia has been often used to describe what was really bronchopneumonia. For Roussy and Leroux[214] found that among 300 necropsies at the Hospice Paul Brousse there were 164 cases, or 55 per cent, of bronchopneumonia and only 4 cases, or 1·4 per cent, of lobar pneumonia. The bronchopneumonic areas are triangular with the base towards the pleural surface, and indeed are infarcts, due to pre-existing endarteritis obliterans which disposes to secondary infection. In 110 out of the 164 cases of bronchopneumonia there was arterial thrombosis, which was of older date than the infected areas of infarction and bronchopneumonia.
Senile tuberculosis, contrary to what has sometimes been stated, is fairly common though it is often latent; a patient with pulmonary tuberculosis may have little or no cough, expectoration, fever, or night sweats, and the physical signs, if present, may be regarded as those of bronchitis and emphysema or bronchiectasis, unless the sputum is available and examined for bacilli. Such unrecognized cases are an obvious danger in institutions, and it may be added that hereditary disposition plays a much less important part in the aged than in early life. Senile tuberculosis, however, is usually either a persistence of that infection or a recrudescence of quiescent infection, and is seldom primary. The disease may be chronic or acute, and either local or generalized.
The senile heart has attracted much attention, and myocardial degeneration and fibrosis due to past infections or to coronary arteriosclerosis are extremely common. The myocardial change is of great importance in reducing the reserve power of the heart, so that cardiac failure is prone to supervene in acute infections, such as influenzal pneumonia. Chronic valvulitis akin to and associated with arteriosclerosis is common; the mitral valve is often affected and incompetent, with a loud systolic murmur at the apex which is displaced outwards; but the most characteristic lesion of advanced years is pure aortic stenosis; this is commonly regarded as part of the arteriosclerotic process in the aorta, but, as I have often noticed, the aorta may be remarkably healthy and even thinner than usual in old people with extensive calcification of the valves reducing the aortic orifice to a chink; it has indeed been thought that such stenosis of the aortic valves may protect the aorta from strain and so from arteriosclerosis. Although involvement of the bundle of His giving rise to the symptom complex of Stokes-Adams disease, and angina pectoris may complicate aortic stenosis, the presence of this valvular defect is compatible with remarkable prolongation of life. This may be due to the more placid life of these old patients, as is suggested by Sir Clifford Allbutt,[215] who regards aortic stenosis as more unfavourable in persons under 55 years of age than in their elders.
Aneurysm of the large arteries is rare in the aged, although arteriosclerosis is common. Diffuse dilatation especially of the arch of the aorta and of the common iliacs is not infrequent, and occasionally latent saccular aneurysms are present. In rare instances large abdominal aneurysms causing pain or remaining latent until rupture occurs are reported. Among 112 abdominal aneurysms collected by Nunneley[216] 15 were over 50 years of age; these figures included 32 from St. George’s Hospital, three of them being over 65 years of age. Miliary aneurysms are of course extremely common in the subjects of cerebral haemorrhage.
Spasm, especially of arteriosclerotic vessels, may be responsible for attacks of giddiness or faintness, particularly on exertion, and there may be some doubt whether such symptoms are the outcome of cerebral anaemia or of cardiac insufficiency. Frequent transient attacks of aphasia or paralysis, due to spasm of arteriosclerotic middle cerebral arteries, may occur in patients with high blood pressure (Peabody,[217] Osler[218]).
Varicosity either localized, like aneurysms, or throughout the length of veins, are common, especially in the lower limbs of women who have borne children and done much standing; this condition disposes to varicose ulcers in the lower third of the leg, and to acute phlebitis. As pointed out by Trousseau, who was an illustration of his own dictum, venous thrombosis may occur in the course of intra-abdominal malignant disease.
Though dyspepsia of adult life often diminishes or passes away in the more tranquil conditions of old age, it is common; Fenwick[219] estimated that it occurred in 21 per cent of the population over the age of 65. Oral sepsis may be responsible for chronic gastritis and much debility in the old. Constipation often comes on after 60 and is mainly due to atonic dilatation and failure of peristalsis in the colon, though diminished secretion of mucus may play a part. Prostatic enlargement has been thought to interfere with peristalsis (Hollis[220]), and in women large fibromyomas of the uterus may have this effect. Gerontal constipation is usually more troublesome in women than in men. Faecal accumulation in the rectum is a frequent cause, especially in bed-ridden subjects, of what they describe as diarrhoea, the real significance of which may be easily overlooked unless digital examination of the rectum is undertaken. The pecten band of fibrous tissue arising in the submucosa of the pecten, inside the external sphincter, narrows the anal orifice and so prevents complete evacuation of the rectum and diminishes the size of the faeces which are generally voided in short pieces. It is usually, but not always, associated with internal piles and due to the attendant congestion. W. E. Miles,[221] who described the pecten band, tells me that it may be regarded as a pathological development of advancing years, and that he has found that it may so reduce the anal orifice in the elderly that it is with difficulty the little finger can be introduced. Pruritus ani, due to piles and local congestion, is not uncommon in the aged.
Piles are common in the aged and are related to the frequency of constipation. Like other diseases, they do not give rise to discomfort so soon or so forcibly as in younger persons. From muscular atrophy hernia, umbilical in both sexes, in men inguinal and in women femoral, is prone to occur.
Gallstones are more frequent in advanced life, especially in women, than at other times of life, gallstones being found after death in about a third of persons over 70 years of age, though, as mentioned elsewhere, biliary colic is comparatively rare in old age.
The urinary bladder in cases of prostatic enlargement shows hypertrophy succeeded by dilatation, fasciculation, and sacculation in response to the obstruction to micturition and degeneration of the muscular fibres. The ureters in similar circumstances become dilated, and the incidence of cystitis and pyelonephritis is thus favoured.
Arthritic Affections.—Although gout is due to a defect in protein metabolism analogous to diabetes mellitus as regards carbohydrate metabolism and to obesity as a manifestation of disordered metabolism of fat, reference to this disease may be made here. Heredity has a potent influence on the incidence of the disease particularly in early life, but acquired gout is essentially a disease of the latter part of life or the early stage of old age when degeneration is beginning. The first attack may not occur until old age, and is then usually mild in character, and, in Sir William Roberts’s[222] words, appears almost as if it were an incidence of senescence. How far the various conditions spoken of as irregular gout, goutiness, or paragouty diseases, which are so numerous as to recall Murchison’s lithaemia, should be regarded as gouty is uncertain, but that they depend on disordered protein metabolism is highly probable. The connexion of gout with infection, as urged by Llewellyn,[223] has a bearing on the fibrositis and Dupuytren’s contraction often regarded as gouty phenomena. Dupuytren’s contraction of the palmar fascia, which has been thought in some instances to be secondary to arteriosclerosis of the medulla oblongata (Jardini[224]), often accompanies the fibrous pads on the interphalangeal joints of the fingers described by Garrod[225] and Hale-White.[226] The tendency of focal infections, especially oral sepsis, to become more frequent with advancing years also has a distinct bearing on the occurrence of chronic infective arthritis of various forms. The most characteristic is morbus coxae senilis which is not uncommonly associated with Heberden’s nodi digitorum, and sometimes with Morrant Baker’s cysts due to distension of synovial bursae with fluid; it may be confused with sciatica. Heberden’s nodes are unimportant and commonly free from attendant symptoms.
Spondylitis deformans with ankylosis of the articulations and ossification of the ligaments of the spine, in some cases further complicated by an extension of the process to the proximal joints of the limbs (rhizomelic spondylitis), may occur in the aged though also earlier in life.
Osteitis deformans or Paget’s disease of bone begins as a rule in the later half of life, the average age being 50 years. Lannelonge[227] and Fournier[228] argued that it is a lesion due to congenital syphilis; but although luetic periostitis and osteitis may imitate it, there is no convincing evidence in favour of their contention.