The functions of an aging individual show in the totality of the changes of the metabolic and neurohormonal modulation.
The dominant feature in elderly people is a great liability under stressful conditions', as a consequence there is a decrease in the total water content of the body and hydroelectrolytic turnover, as well as cellular and humoral dysmetabolisms. Advancing age brings about a general anabolic deficit, a reduction of tolerance of carbohydrates, an increasing in biochemical values of lipids and hemocoagulation components, and a diminution of the cellular energetic potential. Each of the functions having its own development and aging time-table.
Gerovital-H3 ® has a positive effect on the cell metabolism and on the cell membrane. There are studies where the emphasis was placed on Gerovital-H3 ® intervention in the intermediate metabolism favoring ATP synthesis (1). This hypothesis was based on the discrepancy between the favorable trophic effect and the reduced O2 consumption. This finding seems to point out procaine similarity with antioxidative abilities. Since 1962, Ficher and Klotz (2) insisted on procaine's antioxidative effect. Other studies carried out on yeast (3) pointed out procaine action on the enzymes involved in oxireduction. Research on liver homogenate revealed procaine intervention on oxidative phosphorilation of glucidic metabolism (4).
ENERGETIC METABOLISM (EM)
EM undergoes modifications during the life cycle at the level of energy production, storage, transformation and liberation. The cell oxygen consumption decreases progressively with age: At the age of 20: a man's basal metabolism is of 42.5 1.6 cal/sq.m./h; A female's metabolism is of 36.7 2.7 cal./sq. m./h. At the age of 40: a man's metabolism is of 38 2.9 cal./sq.m./h and 35.9 2 cal./sq.m./h. in females.
However, this diminution of the cellular oxygen consumption is neither regular nor uniform; as a compensation, while tissular activity of oxidative phosphorylation decreases, the glycolytic activity increases and some anaerobic energy-generating processes are intensified.
The reduction of the energetic potential is brought about by the diminution in the number and volume of the mitochondria, of the oxidation substrate and of respiratory enzymes. Unlike other structures, the heart tissue shows an accentuation of oxidative and phosphorylating couplings. The low capacity of an aging organism in pathological conditions reflects the low energetic potential of the cells.
The controversial results of the studies on basal metabolism in the elderly depend on the normal and pathological factors that may influence it. The elderly's physical state, the muscle activity one develops, as well as one's bone pathology, neuromuscular coordination, psychological state and integument's aging degree may influence on production or loss of heat.
With the advance in age, in parallel to the decrease of oxygen consumption, we also may see modifications of the thermoregulation. In conditions of average temperature, the body maintains constant temperature even in advanced ages. However, it presents difficulties for its adaptation to extreme temperatures. As the years pass by, as a consequence of a poorer blood flow in the skin, temperature records has a tendency to decrease, so that the response to the low environmental temperatures will be slower. On the other hand, by the integument aging through atrophy, dryness, reduced elasticity and modifications of the capillaries structure, this diminishes the capacity of water elimination through the skin, explaining the elderly's difficulty of adaptation to caloric stress.
The normal indicators of the lipids metabolism inscribe themselves on a curve with maximum values in the 6th and 7th decades of life. In long-lived people, biochemical constants are significantly equal to those of young adults. Directly related to the quantity of cholesterol, total blood lipids increase at the age of 70 as compared to the values recorded at 30 years. The increase is especially on account of the esterified cholesterol (low density) and of the cholesterol bound to beta-lipoproteins (with a tropism to the vascular wall). The relation of lecithin to cholesterol decreases. Kurth's studies (5) on procaine action on the lipids metabolism recorded favorable results in atherosclerotic subjects in whom the function of the cell membrane was corrected. Also, the arteriosclerotic dysproteinemias became normal as a result of procaine administration. The author noticed the clearing of serum as well as the decrease of cholesterol levels.
In order to point out the antiatherogenous action of Gerovital-H3 ®, Aslan carried out a study on 25 subjects aged 72-90 to procaine treatment for 4-11 years (1); an equal number of patients were used as controls. The author studied lipoprotein lipase activity in vitro as well as different lipids-fractions after both heparin injections and the activation of the endogenous lipoprotein lipase. Lipoprotein lipase activity reached the average values 13.01 2.01 in the treated subjects, as against 8.75 1.77 in the controls (the normal value is 15 1.6). An obvious dislocation of the lipoproteins fractions was noticd after the heparin injection, with the modification of the beta/alpha-lipoprotein gradient (80% in the treated subjects, as against 15% in the controls). The modifications of the coefficient beta/alpha specific to the post-heparin lipoproteins tallied with the lipoprotein lipase enzymatic activity in vitro.
The inference maybe thus drawn is that one of the important links in the atherosclerotic dyslipoidosis chain is also subjected to the eutrophic treatment with Gerovital-H3 ®. This data may be correlated with the reduced number of trombotic accidents in aged subjects treated with Gerovital-H3 ®.
Comparative studies on Gerovital-H3 ® and procaine action carried out by Greppy and Sgardigli (6) showed the higher efficiency of Gerovital-H3 ®. Gordon and colleagues (7,8) conducted comparative studies on American procaine and Gerovital-H3 ®. The experiments revealed too the higher efficiency of Gerovital-H3 ®.
Enzymatic structures and protein biochemistry undergo modifications in elderly people. Quantitative modifications are noted in the activity of monoaminooxydase (MAO), aldolase, myosin, adenosine-triphosphatase and phosphofructokinase. Studies published (9,10) draw attention to the modification induced by aging in the enzymatic activity of the nerve cell as well as to the intervention of procaine at this level. The increased MAO activity could play an important role in the biochemical modifications induced by aging and depressive states. Depressive states have been correlated with the reduction of central amines (11) which is due to the increase of MAO. The anti depressive effect of Procaine (Gerovital-H3 ®) has been pointed out by Bucci and Saunders (12), Siggelkow (13), Cambel (14), MacFarlane (9,10), Zung (15) and other researchers.
The total contents of seric proteins remain unchanged. A modification in the ratio of albumin to globulin will be observed: from 1.38 0.03 at the age of 25 it becomes 1.02 0.02 at the age of 75.
Quantitative modifications are observed in the protein contents of muscles, brain and liver. The net muscle mass decreases. Cytoplasm proteins tend to form inactive complexes, so that the fibrils protein structures increase. A diminution of active protoplasmic mass, and along with it, a reduction of the total potassium content of the body will be observed.
CARBOHYDRATES METABOLISM (CM)
CM presents two important phenomena in the aged:
The accentuation of the anaerobic phase of glycolyse, and in consequence the diminution of oxidative phosphorilation processes;
The reduction of the tolerance to glucose.
The aspects related to the statement of a tolerance reduction to glucose with the advance in age, and to the physiological or physiopathological mechanisms which lead to this situation are not yet completely elucidated. It was considered that there is a "real" decrease of the tolerance to glucose with the advance in age, in both sexes, this being shown by glycemia (fasting blood sugar) and by dynamic tests. Some researchers consider that for each decade of age after 50, the fasting blood sugar increases by 1 to 2mg./dl., and postprandial blood sugar increases by 5 to 6 mg./dl.
There are four age-related factors that are incriminated in bringing about modifications in CM: (Carbohydrate Metabolism)
An inadequate Insulin Input;
Decrease of the body net muscle mass;
Increase of the adipose mass tissue, and
Reduction of the cell sensitivity to Insulin independently of any effect of adiposity.
It is considered that previous estimation as to the influence of age upon the decrease of the tolerance to glucose have been exaggerated, as it is not taking into account among other parameters, the correlation of diabetes mellitus, overweight and other existing chronic diseases.
However, the correlation between fasting blood sugar and advance in age was statistically proved, considering the modifications due to overweight.
As years pass by, a slight unbalance will be observed in the glucose homeostasis. However, this is not an absolute rule and it is more or less accentuated by the frequent association of chronic diseases and obesity.
THE INADEQUATE INSULIN INPUT
A reduced insulin secretion has been initially considered as an important factor in reducing the tolerance to glucose in the elderly. This opinion is being revised today considering the following:
Most of the studies show that the advance in age does not lead to reducing the insulin liberation by a stimulation with glucose;
It has even been demonstrated that plasmatic insulin concentration increase in the old, whence it may be deducted that their intolerance to glucose could be determined by a diminished capacity of plasmatic insulin to stimulate the utilization of plasmatic glucose. It is also supposed that there may be a deficient insulin metabolization- a supposition based on data showing a diminution with age of the plasmatic insulin clearance.
REDUCTION OF THE BODY NET MUSCLE MASS
With the advance in age, a correlation has been stated between a reduction of the muscle mass and the reduced tolerance to glucose.
INCREASE OF THE ADIPOSE TISSUE
It is known that the process of hypertrophy and hyperplasia at the adipocyte level is accompanied by a reduced insulin-receptivity, but the inner mechanism by which obesity is determining it is not explained. On the other hand, during the aging process an increased frequency of obesity is observed. However, replacement of the muscle-mass by adipose tissue takes place even if the body weight remains unchanged. Specific transformation in the adipose tissue, associated to above mentioned, may cooperate in modifying the glucidic homeostasis.
DECREASE OF THE CELL SENSITIVITY TO INSULIN
It was emitted the hypothesis that, with age there might exist a decrease of the cell sensitivity to insulin in the target organs, independently of the degree of obesity.
However, there is not sufficient proof to support this hypothesis which is contradicted by the fact that it is a normal sensitivity to insulin associated to a normal tolerance to orally administered glucose.
On the basis of the above considerations it may be said that:
Glucidic homeostasis is not necessarily modified by the aging process.
When glucidic homeostasis appears to be modified by the aging process, a modification manifested by a reduced tolerance to glucose and apparition of the age-related hyperglycemic syndrome, there may exist a loss of the insulin normal action "in vivo".
A parallel drawn between diabetes mellitus and the aging process suggests that diabetes mellitus could represent a model for the latter and some common elements being observed:
The rigidity of the arterial wall;
An increased incidence of coronary atherosclerosis;
The thickening of the basal membrane of the capillaries;
Anomalies of lipids metabolism.
Gerovital-H3 ®, as an intact molecule, and through diethylaminoethanol (DEAE) and paraaminobenzoic acid (PABA) intervenes in the metabolic regulation.
According to Laborit, substances having this type of action, play an important role in the cellular reactivating, and thus we may deduce an enhancement of activity at the cellular level leads to improved energy levels.