Another approach to the quantitative assessment of aging, based on the same definition – reducing overall viability with age, is to consider the overall viability of the system as an integral of the viability of its parts, which, as applied to the organism, means that the overall viability of the body consists of maintaining vitality (functional resource) of its main organs and systems:
Х = k1 х1 + k2 х2 +….+kn хn, where k is the coefficient, x1 … n is the viability of organs and systems. The definition of individual aging as a biological age is based on this.
The common single cause of aging is manifested by the Main types (common mechanisms) of aging.
A fully formed organism has many non-updated elements at all its hierarchical levels: unique genes, non-dividing cells (for example, nerve cells, including autonomic control centers), non-regenerating structures of organs (alveoli, nephrons, etc.), organs themselves and etc. The loss of non-regenerating elements with age is probabilistic, and therefore in the simplest case, it is described by the same type of formula (Gompertz) as the loss of overall viability. It is the 1-st General Type of Aging. The only possibility at present to combat this aging mechanism: replacement of lost structuring units – mechanical prostheses (e.g., dental care) and transplantation of organs and tissues. l
Age-accumulated of non-functional and toxic elements of different nature is 2-nd General Type of Aging. Activation of the organism’s “cleaning” systems is a well-known and widely used tactic to influence this aging mechanism.
Aging of self-renewing elements of the organism structure (skin, mucous, parenchymal organs, etc.) is determined by a decrease in the rate of their self-renewal by reducing growth factors is the 3-d Main type of aging – regulatory aging. Optimal is the impact on the regulatory centers and the introduction of tissue growth factors.
Global mechanisms of aging are manifested in the form of a variety of particular mechanisms for different structural units of the body, depending on the specific conditions and their structure. The effect on them is symptomatic. However, according to the common mechanisms, private mechanisms are grouped into aging syndromes, common to all effects (and diseases). Effects on them is the most promising at the moment, as you can use conventional remedies.
We have proposed a general model of growth an development and regulatory aging, which consists in disinhibition in the vegetative regulatory center (hypothalamus?) of stimulating cells when inhibiting cells die, which determines growth and development, but if death also affects stimulating regulatory cells, then over time the development program is depleted – regulatory aging. This is essentially and very simple model that describes changes in viability (and mortality as a quantitative criterion of aging in general) during all periods of an organism’s life.
Our formula is analogous to the formula of Gompertz-Makeham:
our formula: m=R*1/ (Ho*Exp (-k1*t) —So*Exp (-k2*t) + c) + A;
Gompertz-Makeham formula: m = Ro * Exp (k*t) + A.
The most important formal differences are:
1. The exponent component, reflecting the age dependent mortality rate, is the result of the interaction of 2 exponents, reflecting stimulatory and inhibitory effects. This allows to simulate the initial shape of the mortality rate charts (1—25 years), characterized by a complex U-shaped.
2. The exponent component is influenced (mainly in its final segment) by the coefficient “c”, reflecting the presence of long-livers persons with a genetically reduced rate of aging. This allows to simulate the final shape of the mortality charts (80—110 years), characterized by a complex S-shaped.
Our it is not empirical, and is based on fundamental biological processes and connects the aging process with the processes of growth and development. Regulatory non-dividing cells of the hypothalamus that produce growth factors in blood can be real morphological substratum (the “h” and “s” cells) of the described mechanism; for peripheral mechanisms – a variety of growing and self-updating proliferating somatic cells, the growth of which is regulated by the level of growth-stimulating factors.
The systemic nature of aging also requires a systematic approach to the diagnosis of aging and its effects.
The book describes the feature requirements for the indicator of Biological age, the components of bioage and the computer system determining of bioage and related indicators, including automatic processing of bioage biomarkers using elements of artificial intelligence.
Another computer system described in the book makes it possible to study aging in detail by studying the dynamics of population mortality using the formula of Gompertz-Makeham and its derivatives.
The use of mortality rate unless the external mortality component (“m-A”) graphs and the mortality rate increment (“d (m)”) graphs reflect the actual biological aging and show that the linear form of the graph (on a logarithmic scale) from the period of the end of growth and development remains the same, and decline in the rate of aging of centenarians.
The superposition of curves, reflecting the actual aging rate, shows that the aging is the same in history until 1950 for a number of countries, however, since the middle of the 20th century, the indicators of biological aging are constantly decreasing. Also increases maximum lifespan and reduces the coefficient k of Gompertz chart.
The effect of reducing the aging rate (“d (m)”) for middle ages is accompanied by the phenomenon of inversion of the overall mortality rate (“m”) for ages of long-livers: the natural “m” decrease, observed for all countries in earlier historical periods, is replaced by an increase in modern times. However, in the “d (m)” charts, it can be seen that the decrease in the aging rate of the long-livers is preserved throughout all historical periods. The latter means that the phenomenon of mortality inversion is associated with the external influences on mortality, and not with a change in the aging rate at this time.
Ways to restore regulatory programs – the most promising direction for the impact on aging.
The problem of recovery and correction of regulatory programs of the brain is central to age biology, since many body functions (sexual, immune, metabolic rate, total hormones and the balance of different types of hormones, nervous trophism, growth program, etc.) undergo drastic changes throughout life precisely because of the programmed changes in the regulatory centers, primarily at the level of the hypothalamus.
The methods of brain embryonic tissue transplantation developed in recent years make it possible to begin work on the restoration of depleted regulatory programs in old animals. The results indicate the fundamental possibility of restoring development programs lost or exhausted with age, as well as, possibly, imposing new programs (for example, during interspecific transplants) in order to influence the aging process in the right direction. An alternative to surgical intervention are the methods of pharmacological or physiotherapeutic activation of the corresponding nuclei of the hypothalamus, as well as the creation of new regulatory centers and pacemakers, including the use of psychotherapeutic techniques, hypnosis, etc.
The regulation of cellular growth at different levels of hierarchical structures