III

MECHANISM OF SENILITY

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

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

1

fragments, or disappears completely. M. Matchinsky 1 has studied the series of events in my laboratory, and I am myself well assured of the importance of the action of macrophags in the atrophy of the ovary.

The phenomena of atrophy in general and of senile decay afford other cases of tissue destruction in which the phago

FIG. 8.-Ovum of a Bitch in process of destruction by Phagocytes, which are full of fatty granules.

cytic character of the process is more modified and obscure than in nerve-cells and ova.

It is well known that progressive muscular debility is an accompaniment of old age. Physical work is seldom given to men over sixty years of age, as it is notorious that they are less capable of it. Their muscular movements are feebler and soon bring on fatigue; their actions are slow and painful. Even old men whose mental vigour is unimpaired admit their muscular weakness. The physical

1 Annales de l'Institut Pasteur, 1900, vol. xiv. p. 113.

correlate of this condition is an actual atrophy of the muscles, and has for long been known to observers. More than half a century ago, Kölliker,1 one of the founders of histology, devoted some attention to this matter, and described the senile modification of muscular tissue in the following words :-"In old age there is a true atrophy of the muscles. The fibres are much more slender; there are deposited in their substance numerous yellow or brown granules and many globular nuclei. These nuclei are frequently arranged in longitudinal series and present such signs of active division as are found in embryonic tissue." Other investigators afterwards made similar observations. Vulpian and Douaud3 have stated that a multiplication of nuclei takes places in the atrophying muscles of the old.

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

The investigators who had recorded these facts thought of them only as curious. It is plain, in the first place, however, that this remarkable and rapid multiplication is a proof that senile atrophy is not due to failure of cell pro

1 Eléments d'histologie humaine, French translation, 1856, p. 222. 2 Leçons sur la physiologie du système nerveux, 1866.

3 De la dégénérescence graisseuse des muscles chez des vieillards. Paris, 1867.

liferation, although the latter has frequently been suggested as the mechanism of senescence. In muscular atrophy, cellmultiplication, so far from failing, greatly increases. We may add muscular atrophy to the blanching of hair and the decay of nerve-cells as another instance showing that senile degeneration is not the result of cells ceasing to be able to

FIG. 9.-Degeneration of striated muscle Fibres from the auricular muscle of a man aged 87 years.

(From a preparation made by Dr. Weinberg.)

multiply. Just as in the atrophy of the brain there is an increase in the volume of neurogloa, the substance in which the neuronophags are found, so also in the atrophy of the muscles there is an increase of muscular nuclei. Along with the increase of nuclei, however, there is an increase of the protoplasmic substance of the fibres known as sarcoplasm. The latter replaces the myoplasm, the specific striated substance of muscles, by a process which must be

regarded as parallel with phagocytosis. In a normal muscle the two substances and the sarcoplasmic nuclei are in equilibrium, but in old age the sarcoplasm and its nuclei increase at the expense of the myoplasm. The equilibrium is destroyed with the result that the muscular power is weakened. In these conditions the sarcoplasm acts phagocytically with regard to the myoplasm, just as the chromophag becomes the phagocyte of the pigment of the hair, or the neuronophag devours the nerve-cell.

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

It is one of the curiosities of senile atrophy that whilst there is hardening or sclerosis of so many organs, the skeleton, the most solid part of our frame-work, becomes less dense, so that the bones are friable, the condition often leading to serious accidents in old people. The bones become porous, and lose weight. It is difficult to believe that macrophags, although they destroy softer elements such as nerve-cells or muscle fibres; can be able to gnaw through a hard material like bone impregnated with mineral salts. As a matter of fact, the mechanism of bone atrophy must be placed in a different category from the phagocytosis of other organs. It is brought about, however, by the agency of cells very like some of the macrophags. These cells contain many nuclei, and are known as osteoclasts. They form round about the bony lamellæ and lead to their destruction, but are incapable of breaking off fragments of bone and dissolving them in their interiors. Although the intimate mechanism of this destructive action