Age-associated Losses Research Articles

Supplemental Material for Age-Associated Losses of Brain Volume Predict Longitudinal Cognitive Declines Over 8 to 20 Years

Supplemental Material for Age-Associated Losses of Brain Volume Predict Longitudinal Cognitive Declines Over 8 to 20 Years

Effects of age and caloric intake on glutathione redox state in different brain regions of C57BL/6 and DBA/2 mice

The main purpose of the present study was to determine whether specific regions of the mouse brain exhibit different age-related changes in oxidative stress, as indicated by glutathione redox state and the level of protein-glutathionyl mixed disulfides. Comparison of 3- and 21-month-old mice indicated an age-related decrease in the ratio of reduced to oxidized glutathione (GSH/GSSG) as well as a pro-oxidizing shift in the calculated redox potential (ranging from 6 to 15 mV) in the cortex, hippocampus, striatum and cerebellum, whereas there was little change in the brainstem. This pro-oxidizing shift in redox state was due to a modest decrease in GSH content occurring in all the brain regions examined, and elevations in GSSG amount that were most pronounced in the striatum and cerebellum. The regional changes in glutathione redox state were paralleled by increases in the amounts of protein-mixed disulfides. A reduction of caloric intake by 40% for a short period (7 weeks), implemented in relatively old mice (17 months), increased the GSH/GSSG ratio and redox potential at 19 months in the same brain regions that exhibited age-related decreases. The effects of age and caloric restriction were qualitatively similar in C57BL/6 and DBA/2 mice. However, young DBA/2 mice, which do not show extension of life span in response to long-term caloric restriction, had lower GSH/GSSG ratios and higher protein-mixed disulfides than age-matched C57BL/6 mice. The current findings demonstrate that oxidative stress, as reflected by glutathione redox state, increases in the aging brain in regions linked to age-associated losses of function and neurodegenerative diseases.

Compensation for age-associated chemosensory losses and its effect on the pleasantness of a custard dessert and a tomato drink

Differences between elderly subjects (n=52, 60-85 years) and young subjects (n=55, 18-35) in their food liking and their olfactory capability were investigated. Two food systems were used: custard desserts and tomato drinks. Flavor enhancement/enrichment, textural change, and/or irritant addition were incorporated as compensatory strategies into these foods. The addition of low concentrations of both cherry flavor and cream flavor to the custard desserts influenced their pleasantness for the majority of the elderly. The addition of cream topping increased the pleasantness of the custard desserts for both the elderly and the young. The elderly equally liked the tomato drinks with no or with low irritant addition, whereas the young generally disliked an irritant addition. However, the food liking of the elderly was not generally increased by these different compensatory strategies. Instead, subgroups were observed for each compensatory strategy, in which applied compensatory strategies led to an increase in product pleasantness. Age-associated losses in olfactory capabilities did not sufficiently explain differences in food liking, as only elderly with similar olfactory capabilities to the young demonstrated a liking of enhanced flavor. The present study does not support the assumption that age-associated impairment in olfactory capability will inevitably lead to changes in food liking.

Role of oxidative stress and protein oxidation in the aging process 1,2

The hypothesis that the rate of oxygen consumption and the ensuing accrual of molecular oxidative damage constitute a fundamental mechanism governing the rate of aging is supported by several lines of evidence: (i) life spans of cold blooded animals and mammals with unstable basal metabolic rate (BMR) are extended and oxidative damage (OxD) is attenuated by an experimental decrease in metabolic rate; (ii) single gene mutations in Drosophila and Caenorhabditis elegans that extend life span almost invariably result in a generalized slowing of physiological activities, albeit via different mechanisms, affecting a decrease in OxD; (iii) caloric restriction decreases body temperature and OxD; and, (iv) results of studies on the effects of transgenic overexpressions of antioxidant enzymes are generally supportive, but quite ambiguous. It is suggested that oxidative damage to proteins plays a crucial role in aging because oxidized proteins lose catalytic function and are preferentially hydrolyzed. It is hypothesized that oxidative damage to specific proteins constitutes one of the mechanisms linking oxidative stress/damage and age-associated losses in physiological functions.

Selectivity of protein oxidative damage during aging in Drosophila melanogaster

The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.

Selectivity of protein oxidative damage during aging in Drosophila melanogaster.

The purpose of the present study was to determine whether oxidation of various proteins during the aging process occurs selectively or randomly, and whether the same proteins are damaged in different species. Protein oxidative damage to the proteins, present in the matrix of mitochondria in the flight muscles of Drosophila melanogaster and manifested as carbonyl modifications, was detected immunochemically with anti-dinitrophenyl-group antibodies. Aconitase was found to be the only protein in the mitochondrial matrix that exhibited an age-associated increase in carbonylation. The accrual of oxidative damage was accompanied by an approx. 50% loss in aconitase activity. An increase in ambient temperature, which elevates the rate of metabolism and shortens the life span of flies, caused an elevation in the amount of aconitase carbonylation and an accelerated loss in its activity. Exposure to 100% ambient oxygen showed that aconitase was highly susceptible to undergo oxidative damage and loss of activity under oxidative stress. Administration of fluoroacetate, a competitive inhibitor of aconitase activity, resulted in a dose-dependent decrease in the life span of the flies. Results of the present study demonstrate that protein oxidative damage during aging is a selective phenomenon, and might constitute a mechanism by which oxidative stress causes age-associated losses in specific biochemical functions.

Age Differences in Perceived Positive Affect, Negative Affect, and Affect Balance in Middle and Old Age

Meta-analysis was used to synthesize findings from 125 studies on age differences in positive affect, negative affect, and affect balance. We found a small age-associated decline of positive affect and affect balance, and a small age-associated increase of negative affect. In addition, a quadratic age trend emerged, showing stronger declines of positive affect and stronger increases of negative affect in older subjects. Looking at changes of specific emotions, we found an age-associated decline of those positive and negative feelings that are associated with high arousal (e.g., feeling excited or upset), and an age-associated increase of positive and negative low-arousal emotions (e.g., feeling relaxed or depressed). Furthermore, older adults from the former communist Eastern European countries showed the strongest age-associated decline of positive affect and the strongest age-associated increase of negative affect. We conclude that age-associated losses in the oldest old and economic hardship make the optimization of subjective well-being increasingly difficult.

Prevention and treatment of osteoporosis in the elderly.

Due to age-associated bone losses, all elderly are prone to osteoporosis, which often leads to fractures. Fractures frequently result in dependency and institutionalization, as well as physical deformities that may lead to respiratory and cardiovascular problems. Currently, no drugs exist to promote new bone formation. Thus care of the elderly focuses primarily on lifestyle modification and increased dietary intake of calcium and vitamin D; decreased intake of caffeine, phosphates, and alcohol; smoking cessation; increased exercise; and drugs. Drugs for preventing osteoporosis include supplemental calcium and vitamin D, hormone replacement therapy, and alendronate. Drugs that enhance bone loss or increase the likelihood of falls should be eliminated, if possible, or the dosages adjusted. Making residences safer will also help to minimize the potential for falls. Drugs for treating osteoporosis include hormone replacement therapy, alendronate, and nasal calcitonin. The prevention and treatment plan is individualized for each patient, taking into account personal preferences, risk factors for osteoporosis and fracture, concomitant diseases and drug therapies, efficacy and tolerance of osteoporosis therapy, quality of life, life expectancy, finances, and health insurance coverage.

Life-span development of odor identification, learning, and olfactory sensitivity.

In the first of three studies, children (aged 8 to 14 years) were found to perform worse than young and middle-aged adults in unprompted identification of doors, with average performance much like that of elderly adults. Comparisons on other tasks, specifically odor threshold, prompted odor identification, and object naming (Boston Naming Test), across the life span (five groups) revealed that children have the same excellent olfactory sensitivity as young adults and merely lack odor-specific knowledge that accumulates slowly through life. Such knowledge apparently accumulates so slowly that age-associated discriminative losses, measurable by early middle age, begin to wear away gains obtained through experience before odors can become overlearned. In the second study, a novel adaptive psychophysical method, the step procedure, confirmed the equivalent sensitivity of children and young adults. In the third study, a paired-associate task illustrated the sluggish course of odor learning. Young adults outperformed children, though the youngest group, first graders, made up ground relatively fast. For children and adults, common odors facilitated performance relative to novel odors. The outcome highlighted the relevance of semantic factors in odor learning irrespective of age.

Dietary Arginine Supplementation Does Not Enhance Lymphocyte Proliferation or Interleukin-2 Production in Young and Aged Rats

Recent studies indicate that supplemental arginine may enhance in vitro lymphocyte mitogenesis. To determine whether dietary arginine could reverse age-associated losses in immune functions, we fed purified amino acid diets to young (2-mo-old) and aged (24-mo-old) Fischer 344 rats. Rats receiving control (1.12% arginine) or supplemented (3% arginine) diets were pair fed to intakes of deficient (0% arginine) rats. Another group was fed the supplemented diet ad libitum. On d 15, responses of splenocytes to phytohemagglutinin (PHA), concanavalin A (Con A), and pokeweed mitogen (PWM) were lower (P less than 0.01), but interleukin-2 (IL-2) production was higher (P less than 0.05) in aged rats than in young rats. At mitogen doses producing maximal stimulation, supplemental arginine did not enhance PHA-, Con A- or PWM-stimulated lymphocyte proliferation; PWM responses at sub-maximal doses were higher in pair-fed supplemented rats than in control or ad libitum supplemented rats (P less than 0.05). Arginine supplements did not increase thymus weights or IL-2 production above controls. In another experiment, weanling rats received control and supplemented diets in amounts equal to the intake of deficient rats for an average of 37 d. Splenocytes were cultured with mitogens at various arginine levels. No diet effect was observed. Mitogenesis was maximal when media arginine approximated normal plasma levels. Our results suggest that supplemental arginine has little effect on lymphocyte proliferation or IL-2 production in healthy young and aged rats.

The age function of hearing—aspects of the epidemiology

This paper gives a general perspective of age changes in hearing thresholds and reviews possible mechanisms for these age-associated hearing losses. Ways in which new technologies might be able, either now or in the foreseeable future, to determine to what extent the various structurally demonstrable age changes are responsible for these measured losses are suggested. It is hoped that, eventually, the extent to which deteriorations in these various structural components of the auditory system contribute to the ageing process in hearing will be quantified.

Testicular function and sexual activity in senescent mice.

The steroidogenic potentials of testes from 6-mo-old and approximately 28-mo-old CB6F1 mice were compared by measuring the secretion rate of 11 steroids produced by testes perfused in vitro. Testes from 6- and 28- to 30-mo-old mice secreted similar amounts of testosterone, but marked differences in the secretion of testosterone biosynthetic intermediates were discovered. Testes of old mice produced significantly more (P less than 0.01) delta 5-steroids than young male mouse testes. The presence or absence of sexual activity among old male mice was not correlated with changes in testicular steroidogenesis or plasma steroid levels. The results suggest that selected alterations in androgen biosynthesis occur during aging, but that the decline in reproductive performance among old mice is not attributable to deficits in testicular steroidogenesis. Rather, age-associated losses in sexual activity may be mediated by disturbances in the central nervous system.

Decline and Restoration of Antibody-Forming Capacity in Aging Beagle Dogs

Abstract The production of antibody to coliphage was studied in young (1 1/2 years) and old (7 to 11 years) beagles. In five old dogs given a single injection of T2 coliphage three of them showed a severe deficiency of antibody-forming capacity as compared to five young controls. When three injections of T2 or T4 coliphage were given in 5 days, 15 old dogs produced the same amount of antibody as did 15 young control dogs. Thus, antibody-forming capacity was restored to aging dogs by giving multiple injections of antigens. The relative serum titer to the cross-reacting antigen, T4 coliphage, was equal in young and old dogs given T2 coliphage. Our results are interpreted in accord with the Antigen Selection Hypothesis (33). They showed that one of the age-associated losses in antibody-forming capacity results from a decline in the proliferative activity of antigen-stimulated cells because the proliferative state can be maintained by repeated injections of antigen. We also concluded that the precursor cells suffer no loss with age in sensitivity to antigenic stimulation because there is no relative increase in the fraction of cross-reacting antibody.