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 Councilman137 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 (Pringle139). These atrophic changes are far commoner on the backs than on the palms of the hands, and it is noteworthy that among Cheatle’s140 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 Bacon142 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 Cameron143 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 Tarente145 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 Sinclair146 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’s147 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 (Monauni148). 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 Clarke150 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 (Hollis151). 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 (Luciani152), but the latter change is not constant, for in a woman of 93 Salimbeni and Gery153 definitely noted that the cells were not atrophied. That such atrophy of the liver cells is pathological is perhaps supported by D. Symmers’s154 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 Leroux155 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 Weber158 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. Charcot159 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; Councilman160 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. Ophülz161 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 (Hansen163), though some have described a secondary anaemia. Thus in a female centenarian Macnaughton164 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. Rolleston165).

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 Hammar166 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-White167). 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. Findlay168 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 Walker170 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 (Launois171) 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. Nemenow172 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). Hertoghe173 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 Mott174 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 Paul175 has pointed out, be compared with prostatic enlargement in the male.