Senescence, the Biological Problem of
The problem of the senescence of organisms is linked to the condition of the life cycle (v. BIOLOGICAL CYCLES). Each species has its own developmental cycle: it grows, reproduces, and then, after a period of senescence, dies. There is also a relationship between senescence and growth, in the sense that, as long as there are manifestations of growth, there is no senescence.
A problem of natural interest and one that helps to clarify the concept of senescence is that which arises in the case of protozoa. According to WEISSMANN’s concept, these animals would be immortal, in the sense that (naturally from a theoretical point of view) they never age and never die because, through reproduction, they escape the fatal destiny of all living beings. Indeed, a protozoon, at a given moment, and still in the fullness of its vitality, divides and gives rise to two organisms, which are also young like the parent. Two new organisms are thus formed, without the first having aged or died. If one cannot speak of senile phenomena in these unicellular organisms, the phenomenon of death can, however, be observed in the sense that, after a certain number of generations, nothing remains of the matter that constituted the body of the initial parent. In multicellular animals, on the other hand, a life cycle is established that culminates in death. Generally, death is preceded by a period of senescence.
It has been suggested that the phenomenon of senescence can be explained by a process of dehydration to which the organism is subject from the earliest age, or, to be more precise, even before birth, during embryonic and fetal development. Consider that, while in a human embryo 97% of its body weight is due to water (almost all water), at 8 months of intrauterine life the water constitutes 80% of the newborn, 70% in the adult, and almost 58% in the elderly. The phenomenon of “colloidal hysteresis” has also been considered as a factor in senescence: this term indicates the increasing difficulty of a hydrophilic colloidal substance to pass from a gel to a sol condition and vice versa, i.e., the increasing difficulty of reversibility. And since it has been demonstrated that in the living cell there is a continuous reversibility, and on the other hand that all colloids are subject to this law of aging, it is easy to understand how this phenomenon has been applied to explain aging in a biological sense. Other factors invoked are that of gradual mineralization and that of the gradual accumulation of catabolites in relation to a growing difficulty of permeability of the cell membrane to the passage of these products, which are thus retained within the cells themselves.
While these facts can certainly be recognized during the phenomena of senescence, they should not, however, be attributed the value of causal factors. The true and only factor is another, and all the phenomena so far considered are merely consequences. The true factor is cellular differentiation: this is a notable privilege of multicellular animals, which allows for the highest functions but condemns the organism to a limited life cycle. The cells of metazoan associations of higher organization, by the principle of the division of labor, differentiate by assuming the structures most suited to the various functions for which they specialize. But with this cellular specialization, the cell loses the ability to divide and reproduce, and this leads to the senescence of the cell, during which the now-described phenomena of dehydration, colloidal hysteresis, mineralization, etc., occur and inevitably lead to death.
That this is the true cause of senescence and death is demonstrated by many experiments: if one cultures the cells of a higher organism, as Carrel did with cells from the heart of a chicken embryo, and prevents these cells from differentiating by means of embryonic juices, they multiply theoretically indefinitely: a strain has been cultivated for over 26 years, a period well beyond the normal life cycle of the chicken. This also explains why, with their multiplicative activity, senescent conditions do not occur in the cells of the germ line, and theoretically all could give rise to new organisms; this condition led Weissmann to extend his principle of immortality even to the germ-line cells of metazoans.
By studying the life cycle of an animal and the cycle of cells, it is found that only in a few tissues do the cycles coincide. Among these are nervous tissue and striated muscle tissue. In these tissues, the cells lose the ability to multiply from the first days of embryonic life and differentiate, accompanying the individual throughout life. These are the tissues that Bizzozero defined as “permanent elements.” In the cells of these tissues, senile phenomena are observed that coincide with the senescence of the organism. But in very many other tissues, the life cycle of the cells is very short, and many are produced, differentiate, age, and die within the space of a few weeks. These are the tissues of “labile elements” of Bizzozero, those in which functional wear necessarily leads to a short life cycle. The cells of our epidermis are cited as an example: they continuously die and, after forming the horny layer, detach and are eliminated from the organism. This continuous “death” of our tissues is possible because there is a zone of the tissue in which cell differentiation does not occur and in which proliferative activity is preserved. Thus, even these cells of the “cambial” tissues, to use the botanists’ term, which are always actively multiplying, never age, just as the cells of the germ line do not age. It is the multiplicative activity, which continuously renews them, that prevents the fatal process of senescence from manifesting itself. Thus, the germinal layer of the skin of an octogenarian has the same structure and the same youthfulness as that of a newborn.
Therefore, to study the phenomena of cellular senescence, we must refer above all to the permanent cells, i.e., those that accompany the individual throughout the entire life cycle. For example, the picture of senescence in nerve cells is interesting: the cell shape changes, special outgrowths, the so-called paraplasms, are produced, “fenestrated” cavities form, and accumulations of melanin pigment and fat droplets occur. The accumulation of pigment and fat are two of the most striking and common manifestations of cell senescence.
If one considers the organism as a whole, it is found that, more than the general phenomena now recalled,