Myocontrol in aging

Myoelectric (EMG) signals are used in assistive technology for prostheses, computer and domestic control. An experimental study previously conducted with young participants was replicated with elderly persons in order to assess the effect of age on the ability to control myoelectric amplitude (or myocontrol). Participants performed pointing tasks as the myoelectric amplitude was captured by a surface electrode in two modalities (sustained: stabilize the amplitude after reaching the desired level; impulsion: return immediately to resting amplitude). There was a significant decrease of performance with Age. However, the patterns of performance of young and aged were noticeably similar. The Impulsion modality was difficult (high rates of failure) and the speed-accuracy trade-offs predicted by Fitts' law were absent (bow-shaped patterns as function of target amplitude instead of logarithmic increase). Conversely, the reach phase of the Sustained modality followed the predictions of Fitts' law. However, the slope of the regression line with Fitts' index of difficulty was quite steeper in aged than in young participants. These findings suggest that 1) all participants, young and aged, adapt their reaching strategies to the anticipated state (sustained amplitude or not) and/or to the difficulty of the task, 2) myocontrol in aged persons is more fragile, i.e., performance is markedly degraded as the difficulty of the task increases. However, when individual performance was examined, some aged individuals were found to perform as well as the young participants, congruently with the literature on good aging.     

Mitochondrial bioenergetics in aging

Mitochondria are strongly involved in the production of reactive oxygen species, considered as the pathogenic agent of many diseases and of aging. The mitochondrial theory of aging considers somatic mutations of mitochondrial DNA induced by oxygen radicals as the primary cause of energy decline; experimentally, complex I appears to be mostly affected and to become strongly rate limiting for electron transfer. Mitochondrial bioenergetics is also deranged in human platelets upon aging, as shown by the decreased Pasteur effect (enhancement of lactate production by respiratory chain inhibition). Cells counteract oxidative stress by antioxidants; among lipophilic antioxidants, coenzyme Q is the only one of endogenous biosynthesis. Exogenous coenzyme Q, however, protects cells from oxidative stress by conversion into its reduced antioxidant form by cellular reductases.     

Premature aging in uremia

Guanidinosuccinic acid is an aberrant metabolite isolated 40 years ago in the blood and urine of uremic subjects and a suspect in the toxicity associated with renal failure. It plays a minor role in the bleeding diathesis of uremia, contributes to the methyl group deficiency of dialysis patients, and is a factor in the premature atherosclerosis of end stage renal disease through the induction of hyperhomocysteinemia. As a major player, however, in the diversity and severity of uremic symptoms, it is a disappointment. Recently its source has been identified. It results from the superoxidation of argininosuccinic acid, which leads, also, to the production of gamma glutamic semialdehyde, an advanced glycation end product (AGE), which normally results from from the Maillard reaction, the non-enzymatic browning of protein. AGEs stimulate cross-linkages in protein that lead ultimately to loss of function, phagocytosis, and removal, and are important elements in the premature aging characteristic of renal disease, and diabetes.     

Free radicals in aging

Summary Aging is the progressive accumulation of changes with time that are responsible for the ever-increasing likelihood of disease and death. These irreversible changes are attributed to the aging process. This process is now the major cause of death in the developed countries. This fact is obscured by the protean nature of the contributions of this process to the events which terminate life.The aging process may be due to free radical reations. This theory is supported by: 1) studies on the origin and evolution of life; 2) the numerous studies of the effect of ionizing radiation on living systems; 3) life span experiments in which the diet was modified so as to alter endogenous free radical reaction levels; 4) the plausible explanations it provides for aging phenomena; and 5) the growing number of studies which implicate free radical reactions in the pathogenesis of specific diseases.The relationship between aging and diseases involving free radical reactions seems to be a direct one. Modulation of the normal distribution of deleterious free radical reaction-induced changes throughout the body by genetic and environmental differences between individuals results in patterns of change, in some sufficiently different from the normal aging pattern to be recognized as disease. The growing number of free radical diseases includes the two major causes of death, cancer and atherosclerosis.It is reasonable to expect on the basis of present data that a judicious selection of diets and antioxidant supplements will increase the healthy, active life span by 5–10 or more years.     

Action of estrogens in the aging brain: Dementia and cognitive aging

Background

Menopause is associated with sharp declines in concentrations of circulating estrogens. This change in hormone milieu has the potential to affect brain functions relevant to dementia and cognitive aging.

Scope of review

Focused review of published results of randomized clinical trials of estrogen-containing hormone therapy for Alzheimer's disease treatment and dementia prevention, observational research on cognition across the menopause transition, and observational research on the association of hormone therapy and Alzheimer's disease risk.

Major conclusions

Clinical trial evidence supports conclusions that estrogen therapy does not improve dementia symptoms in women with Alzheimer's disease and that estrogen-containing hormone therapy initiated after about age 65 years increases dementia risk. Hormone therapy begun in this older postmenopausal group does not ameliorate cognitive aging. Cognitive outcomes of midlife hormone exposures are less well studied. There is no strong indication of short-term cognitive benefit of hormone use after natural menopause, but clinical trial data are sparse. Little research addresses midlife estrogen use after surgical menopause; limited clinical trial data imply short-term benefit of prompt initiation at the time of oophorectomy. Whether exogenous estrogen exposures in the early postmenopause affect Alzheimer risk or cognitive aging much later in life is unanswered by available data. Observational results raise the possibility of long-term cognitive benefit, but bias is a concern in interpreting these findings.

General significance

Estrogen-containing hormone therapy should not be initiated after age 65 to prevent dementia or remediate cognitive aging. Further research is needed to understand short-term and long-term cognitive effects of estrogen exposures closer to the age of menopause.     

Cardiac aging

Health care for the elderly in western society has emerged as an increasingly important economic and political issue in recent years. As the elderly proportion of western populations continues to expand, maintaining health and wellness of the aged will continue to be an important research priority in the near future. This review will attempt to briefly highlight what is known about age-related changes in cardiac performance in humans, then focus on recent work on cellular mechanisms of cardiac deterioration in vertebrate models. The final section will discuss the implications of work done in the nascent fruit fly model system for aging cardiac function and conclude by outlining potential future uses for invertebrate cardiac model systems.     

Carcinogenic aging

In ours and other studies, data have been obtained testifying to the fact that, under the action of various classes of chemical carcinogenic agents (polycyclic aromatic hydrocarbons, nitrous compouds, aromatic amines), other mutagens, ionizing radiation, extremely low frequency (50 Hz), electromagnetic fields (EMFs), constant illumination, and smoking, in the basic homeostatic systems of an organism (nervous, endocrine, immune, and energy homeostasis) premature hormonal, and metabolic shifts occur similar to those arising during physiological aging. These shifts create favorable conditions for the promotion and progression stages of carcinogenesis. The use of genetically modified animals (mutant, transgenic, or knockout) opens new possibilities for analyzing the role of individual genes in the interrelationships between processes of natural and accelerated, by environmental factors, aging. For genetically modified mice with phenotypic signs of accelerated aging, as a rule, the frequency of new-growth development increases, then for animals with decelerated aging, an increase in the latent period of tumor development and/or a decrease in the frequency of their appearance is noted. The application of geroprotectors under conditions of increased risk of accelerated aging resulting genetically or from adverse environmental factors (carcinogens, mutagens, peculiarities in diet) can be a first line prevention against cancer.     

Immunological aging

Immune responses decline with age, as assessed by the increasing role of infections in elderly subjects. This decline is, however, very progressive, and usually only clear-cut after 80 years of age. Major difficulties have been encountered to delineate the cellular basis of this immunodeficiency, which is subtle and inconsistent, at the origin of contradictory reports. This is, however, an important challenge in view of the possible therapeutic perspectives of immunotherapy of aged subjects.     

Orthostatic hypotension in aging humans

We tested the hypothesis that hypotension occurred in older adults at the onset of orthostatic challenge as a result of vagal dysfunction. Responses of heart rate (HR) and mean arterial pressure (MAP) were compared between 10 healthy older and younger adults during onset and sustained lower body negative pressure (LBNP). A younger group was also assessed after blockade of the parasympathetic nervous system with the use of atropine or glycopyrrolate and after blockade of the beta(1)-adrenoceptor by use of metoprolol. Baseline HR (older vs. younger: 59 +/- 4 vs. 54 +/- 1 beats/min) and MAP (83 +/- 2 vs. 89 +/- 3 mmHg) were not significantly different between the groups. During -40 Torr, significant tachycardia occurred at the first HR response in the younger subjects without hypotension, whereas significant hypotension [change in MAP (DeltaMAP) -7 +/- 2 mmHg] was observed in the elderly without tachycardia. After the parasympathetic blockade, tachycardiac responses of younger subjects were diminished and associated with a significant hypotension at the onset of LBNP. However, MAP was not affected after the cardiac sympathetic blockade. We concluded that the elderly experienced orthostatic hypotension at the onset of orthostatic challenge because of a diminished HR response. However, an augmented vasoconstriction helped with the maintenance of their blood pressure during sustained LBNP.     

Apoptosis in the aging process

Although many hypotheses have been proposed to explain the aging process, the exact mechanisms are not well defined. Recent accumulating evidence indicates that dysregulation of the apoptotic process may be involved in some aging processes; however, it is still debatable how exactly apoptosis is expressed during aging in vivo. In this review, we discuss recent findings related to apoptosis of individual organs during aging and their significance. We demonstrate that aging enhances apoptosis and susceptibility to apoptosis in several types of intact cells. In contrast, in certain genetically damaged, initiated, and preneoplastic cells, aging suppresses these age-associated apoptotic changes. In various cells, apoptosis enhances the elimination of damaged and dysfunctional cells presumably caused by oxidative stress, glycation, and DNA damage. In these cases, the incidence of apoptosis correlates with the level of accumulated injury. It is concluded that apoptosis plays an important role in the aging process and tumorigenesis in vivo probably as an inherent protective mechanism against age-associated tumorigenesis.     

Recent developments in yeast aging

In the last decade, research into the molecular determinants of aging has progressed rapidly and much of this progress can be attributed to studies in invertebrate eukaryotic model organisms. Of these, single-celled yeast is the least complicated and most amenable to genetic and molecular manipulations. Supporting the use of this organism for aging research, increasing evidence has accumulated that a subset of pathways influencing longevity in yeast are conserved in other eukaryotes, including mammals. Here we briefly outline aging in yeast and describe recent findings that continue to keep this “simple” eukaryote at the forefront of aging research.     

Phosphorylated dolichols in aging.

The age-associated changes in the levels and synthesis of dolichyl phosphate and dolichyl diphosphate derivatives were investigated in brain and liver of 057B1/NNia mice. The total chloroform/methanol (2:1, v/v)-extractable phosphorylated dolichols of brain increased from 1.01 micrograms/g at 3 months to 5.22 micrograms/g at 28 months of age. The long-chain dolichyl diphosphate oligosaccharide (Dol-PP-oligo) levels of brain increased from 0.82 microgram/g in 3 months to 2.8 micrograms/g in 28-month-old animals. However, in liver and in kidney, the levels of these components were unaffected by age. Incorporation of labelled glucose from UDP-glucose into dolichyl phosphate glucose and Dol-PP-oligo in brain microsomes was unaffected by age, whereas, in liver microsomes, the rates of synthesis of both components increased by 50-150%. The increased rate of synthesis and lack of accumulation of Dol-PP-oligo in liver suggest an active utilization and/or catabolism of these glycoprotein precursors. The accumulation of Dol-PP-oligo in aging brain may reflect its decreased utilization for N-glycosylation and/or reduced catabolism.