摘要:

Though intrinsic mitochondrial aging has been considered before as a possible cause of cellular senescence, the mechanisms of such mitochondrial aging have remained obscure. In this article we expand on our hypothesis of free-radical-induced inhibition of mitochondrial replenishment in fixed postmitotic cells. We maintain that the respiration-dependent production of superoxide and hydroxyl radicals may not be fully counteracted, leading to a continuous production of lipoperoxides and malonaldehyde in actively respiring mitochondria. These compounds, in turn, can easily react with the mitochondrial DNA which is in close spatial relationship with the inner mitochondrial membrane, producing an injury that the mitochondria may be unable to counteract because of their apparent lack of adequate repair mechanisms. Mitochondrial division may thus be inhibited leading to age-related reduction of mitochondrial numbers, a deficit in energy production with a concomitant decrease in protein synthesis, deterioration of physiological performance, and, therefore, of organismic performance.

ISSN:0304-324X    

DOI:10.1159/000212510

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Rhythmicity is a fundamental property of living matter: biological rhythms in man as well as in other organisms can be demonstrated at all levels of organization (population, group, individual, organ, tissue, cell and subcellular structure). From a macroscopic point of view a rhythm implies regular periodicity of data displayed as a function of time. With the help of computers and special programs, it is possible to obtain a microscopic characterization and quantification of rhythm. A biorhythm can be characterized by the statistical estimation of several parameters: the period, the acrophase, the amplitude, the mesor. Each of these parameters is expressed as a mean with its confidence limits for a degree of security of 95%. With reference to the period, rhythms can be analyzed as a spectrum with several spectral domains: circadian rhythms (with period of about 24 h) are the most carefully studied, but other rhythms exist such as ultradian rhythms (period 28 h, e.g. circamensual, circannual...). The acrophase is the peak time of the sine function used to approximate the rhythm. The amplitude is equal to half of the total rhythmic variability. The mesor is the mean adjusted rhythm; it corresponds to the 24-hour mean when sampling is performed at equal intervals. Circadian rhythms in blood variables are now fairly well documented in young healthy adults. Reports dealing with circadian rhythms in elderly subjects are few for obvious reasons, including the difficulty of gathering a group of elderly subjects comparable in age and social synchronization and moreover, free of major liver, heart, kidney, bone or any other degenerative disease and, consequently, not requiring medication. Therefore, we have undertaken a comparative study of the circadian rhythms in a group of 7 young healthy medical students (mean age 24 years) and in 18 elderly persons, free of the aforementioned diseases (mean age 80 years; 6 elderly men, 6 elderly women, 6 elderly women and men suffering from senile dementia). All subjects, either young or aged, were synchronized with respect to meal timing, diurnal activity and nocturnal rest. Blood samples were drawn at fixed times, every 4 h, during a single continuous span of 24 h beginning at 07.45 h (circadian rhythm) and the sampling was renewed four times a year to gather data on the circannual variations. Several biochemical variables were assayed, including electrolytes, enzymes, hormones. From these studies, it appears that the parameters characteristic of the biological rhythm may be modified with aging. However, the modifications are different from one function or variable to another. Differences in acrophases, mesors and amplitudes could be demonstrated. For instance, the acrophase may be shifted in the elderly for magnesium, calcium, proteins or some steroids, or on the contrary, it may be remarkably steady, e.g. for adrenal steroids, melatonin. The administration as a function of time of drugs or agents used as a diagnostic tool allowed to ascertain the importance of the time structure in this field. Both validity and interpretation of such administration depend upon the timing of the agent administration in the 24-hour scale. Therefore, the temporal organization of the subjects undergoing such treatments should be taken into account. One may presume that in a near future this type of investigation on various biological variables may lead to an improvement of the desired drug effects. Thus, the important changes observed in total serum proteins in the young and the aged, as well as the differences in the localization of their peak troughs, depending on the group, must be taken into consideration with regard to the roles played by serum proteins, in particular in the binding of several molecules, including hormones and drugs.

ISSN:0304-324X    

DOI:10.1159/000212573

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Among gerontopsychiatric drugs, Hydergine is pharmacologically characterized by agonist action at central dopamine and serotonin receptors. This review presents a summary of the results obtained with Hydergine in numerous controlled trials in patients with senile mental impairment. Assessment was carried out by means of a rating scale (mainly the Sandoz Clinical Assessment Geriatric, or SCAG, scale), psychometric tests (e.g. the Nuremberg Geriatric Inventory, or NGI), and the EEG. Hydergine also lowers serum prolactin, though a correlation with clinical improvement has not been established as yet. In the discussion, the need for objective, measurable and precise indicators in gerontopsychiatry is stressed.

ISSN:0304-324X    

DOI:10.1159/000212511

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

As people grow older, their subjective and objective sleep patterns change: sleep is often experienced as less deep, more broken, less refreshing – and these alterations find their objective correlate in polygraphic sleep recordings. Reductions in high amplitude slow wave sleep, rapid eye movement (REM) sleep and sleep maintenance are the best documented of these. Besides, there are changes in the EEG pattern during sleep (fewer and slower sleep spindels, fewer K-complexes and other phasic events). Daytime EEG recordings in the elderly are characterized by slowing of the dominant alpha rhythm, diffuse or localized slow waves and reduced reactivity to stimuli. Only few studies, however, have addressed the question of how daytime EEG alterations are related to changes of the sleep polygram, and how these electrophysiological parameters relate to measures of mental performance which also undergo changes with aging. A review of published results and data from our own studies suggest that, within the non-pathological range, few correlations exist between polygraphic sleep, daytime EEG and mental performance data if age as an independent factor is kept constant. The only relations that were significant in some of the studies had opposite directions in different subjects’ samples. Thus, until more is known, these 3 areas of assessment should be studied and conceptualized separately. Our lack of understanding in this field is further illustrated by results of drug studies: compounds with confirmed effects on mental performance and mood in young subjects, such as amphetamine, fail to be useful stimulants or antidepressants in the elderly, and drugs like co-dergocrine mesylate (Hydergine ®) which are of use in mentally deteriorating old persons have no effects on vigilance and mental performance in young, healthy subjects. Therefore, extrapolations from one level of assessment to another and from experiments in young subjects to studies in the elderly appear unwarranted at the present

ISSN:0304-324X    

DOI:10.1159/000212574

出版商:S. Karger AG    

年代:1982

数据来源: Karger

ISSN:0304-324X    

DOI:10.1159/000212512

出版商:S. Karger AG    

年代:1982

数据来源: Karger

ISSN:0304-324X    

DOI:10.1159/000212513

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

It is generally agreed that, irrespective of age, patients with sustained hypertension should receive antihypertensive therapy. This general attitude contrasts with the lack of knowledge of how drug response and drug sensitivity are changed in the elderly. Besides pharmacokinetic processes it is the physiology and pathophysiology of the elderly that modify the specific response to antihypertensive drugs and the adverse reactions related. The elderly and in particular those with cerebrovascular disease are susceptible to postural hypertension because they have less responsive baroreflexes. For this reason, adrenergic neuron-blocking drugs should not be used for treatment. The routine use of diuretics implies an enhanced risk of hypokalemia in the elderly especially if digoxine is applied in addition. The glucose tolerance gets more easily deteriorated than in younger patients. Thus, there are relatively few antihypertensive agents left for the optimal treatment of hypertension in the elderly. β-Block-ing drugs and co-dergocrine appear to be appropriate for basic therapy. Both agents are efficacious without inducing postural hypertension or improper sedation. In this paper the results of two studies are demonstrated dealing with the antihypertensive spectrum of the β-blocker pindolol and of co-dergocrine, respectively. The first study comprised 7,062 patients with an age range from ≤ 30 to ≥ 70 years. The comprehensive material offered the opportunity of analyzing the age dependency of the responsiveness to β-blockade. With an initial systolic blood pressure of 180–190 mm Hg the mean pressure drop due to pindolol (15mg/day) decreased by 40 mm Hg on the average in patients ≤ 20 years and by 20 mm Hg in those ≥ 70 years with the age-groups between showing an intermediate response. The diastolic pressure reduction, however, does not show a comparable age dependency. The same applies to the regulation of heart rate at rest. Thus, altogether the antihypertensive pattern of β-blockade is modified by the age factor to a minor degree only. In terms of daily antihypertensive treatment the differences of response due to age can be neglected. The trial on co-dergocrine (6–12 mg p.o./day) in 115 patients revealed similarities to the β-blocking agent regarding the influences on blood pressure and heart rate. Co-dergocrine induced an equieffective reduction of the blood pressure in the sitting and upright positions. The advantage of that drug compared with β-blocking agents is the lack of potential side effects related to cardiac depression. The paper refers to another study that centered on the age-dependency of side effects related to central active hypertensive agents. The corresponding trial on guanfacine (n = 4625) revealed no relevant differences in side effects due to the age factor, either in terms of their frequ

ISSN:0304-324X    

DOI:10.1159/000212575

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

The influence of age and smoking on pharmacokinetics of pindolol and propran-olol was investigated. Although there was a statistically significant difference in certain phar-macokinetic parameters (maximum plasma concentration, area under the curve, elimination constant and elimination half-life) between elderly patients (more than 60 years) and young persons (20–30 years) no significant differences were found as far as smoking and nonsmoking is concerned. This is in contrast with some reports in the literature. The higher plasma concentrations of both investigated drugs may be the result of a decreased metabolism of pro-pranolol in older persons, in a decreased hepatic blood flow and a decreased renal elimination. Because of the lower sensitivity of β-receptors in old persons, the higher plasma concentrations of β-receptor blockers in this group of patients should not result in a diminished dose of the investigated β-receptor blockers in the eld

ISSN:0304-324X    

DOI:10.1159/000212576

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

Wherever the age of an individual can, of course, be precisely indicated, the individual physiological state of every aged person varies greatly and therefore the resultant implications considering absorption, distribution, metabolism and excretion. In animals aging has been described as a factor of modification of metabolism. In the elderly the oxida-tive enzyme activity appears diminished but coupled to a decreased liver mass and liver blood flow. Examples of decreased conjugation for paracetamol and indomethacin are known. Ace-tylation does not seem to be influenced. The net effect of aging appears quite frequently an increase in the blood level of unchanged drug. However, drug metabolism cannot be considered independently from the other factors calling for an individualized treatment of the elderly.

ISSN:0304-324X    

DOI:10.1159/000212577

出版商:S. Karger AG    

年代:1982

数据来源: Karger

摘要:

It can be shown that aged patients need about 2/3 of the dose of younger adult depressive patients to reach a comparable serum level distribution. No difference could be found between younger and aged patients in the correlation between serum level and clinical outcome. This correlation can best be described as a kind of saturation curve. Taking the vast serum level range in patient collectives in therapy with tri- and tetracyclic antidepressives into consideration, a routine screening of serum levels of antidepressives is highly desirable.

ISSN:0304-324X    

DOI:10.1159/000212578

出版商:S. Karger AG    

年代:1982

数据来源: Karger