Effects of aging on the kidney.

A host of abnormalities of renal structure and function accompany advancing age. This presentation briefly surveys the renal anatomical and functional changes associated with senescence. Four areas of renal functional change have been selected for in-depth discussion: a) renal blood flow; b) glomerular filtration rate; c) renal sodium handling; and d) renal concentrating ability. The methodologic considerations including population selection which confound the assessment of the effects of aging on renal function are discussed. In addition, the functional changes associated with senescence are discussed in the context of longitudinal studies and studies utilizing appropriate patient cohorts, including potential kidney transplant donors. The clinical implications of senescent changes with regard to adjusting "normative" standards to fit the age of the patient are addressed. Furthermore, the implications of age-related renal functional alterations in predisposing the elderly patient to a number of fluid and electrolyte derangements are considered.--Epstein, M. Effects of aging on the kidney.     

Profiles of random change during aging contain hidden information about longevity and the aging process.

Many different morphological and physiological changes occur during the yeast replicative lifespan. It has been proposed that change is a cause rather than an effect of aging. It is difficult to ascribe causality to processes that manifest themselves at the level of the entire organism, because of their global nature. Although causal connections can be established for processes that occur at the molecular level, their exact contributions are obscured, because they are immersed in a highly interactive network of processes. A top-down approach that can isolate crucial features of aging processes for further study may be a productive avenue. We have mathematically depicted the complicated and random changes that occur in cellular spatial organization during the lifespan of individual yeast cells. We call them budding profiles. This has allowed us to demonstrate that budding profiles are a highly individual characteristic, and that they are correlated with an individual cell's longevity. Additional information can be extracted from our model, indicating that random budding is associated with longevity. This expectation was confirmed, providing new avenues for exploring causal factors in yeast aging. The methodology described here can be readily applied to other aspects of aging in yeast and in higher organisms.     

Glutathione contents of tissues in the aging mouse.

1. Previous results from this laboratory demonstrated that the erythrocyte content of reduced glutathione (GSH) decreased as a function of both increasing cell age and mouse age [Abraham, Taylor & Lang (1978) Biochem. J. 174, 819-825]. In the present investigation glutathione concentrations were determined in other tissues of the C57BL/6J mouse of different ages (6--31 months) throughout the life-span. 2. At all ages the total glutathione and the GSH concentrations in liver were 3 times that in kidney and 10 times that in heart. In the old (31 months) mouse the GSH contents were lower by 30% in the liver, 34% in the kidney and 20% in the heart than in the mature (17--23 months) animals. 3. The oxidized glutathione (GSSG) concentrations of the tissues did not vary with age and constituted less than 3% of the total glutathione. 4. The decreased in GSH concentrations were not due to changes in organ weights, which were constant from 10 to 36 months of age. 5. These findings extend our previous results and indicate that a general characteristic of aging tissues may be a decrease in GSH concentrations. Further, this is consistent with our hypothesis that the reducing potential of tissues decreases in senescence.     

Muscle-specific atrophy of the quadriceps femoris with aging.

We examined the size of the four muscles of the quadriceps femoris in young and old men and women to assess whether the vastus lateralis is an appropriate surrogate for the quadriceps femoris in human studies of aging skeletal muscle. Ten young (24 +/- 2 yr) and ten old (79 +/- 7 yr) sedentary individuals underwent magnetic resonance imaging of the quadriceps femoris after 60 min of supine rest. Volume (cm3) and average cross-sectional area (CSA, cm2) of the rectus femoris (RF), vastus lateralis (VL), vastus intermedius (VI), vastus medialis (VM), and the total quadriceps femoris were decreased (P < 0.05) in older compared with younger women and men. However, percentage of the total quadriceps femoris taken up by each muscle was similar (P > 0.05) between young and old (RF: 10 +/- 0.3 vs. 11 +/- 0.4; VL: 33 +/- 1 vs. 33 +/- 1; VI: 31 +/- 1 vs. 31 +/- 0.4; VM: 26 +/- 1 vs. 25 +/- 1%). These results suggest that each of the four muscles of the quadriceps femoris atrophy similarly in aging men and women. Our data support the use of vastus lateralis tissue to represent the quadriceps femoris muscle in aging research.     

Biotransformation of drugs during aging.

Although the biological half-lives of many drugs appear to be longer in the elderly than in the young, the reasons for these longer half-lives are seldom clear, because the pharmacokinetic data obtained in humans are seldom sufficient to make a proper pharmacokinetic analysis. In the present paper are outlined the kinds of data required, the reasons they are required, and the possible consequences resulting from misinterpretation of inadequate data.     

Drosophila with postponed aging as a model for aging research.

Species of the genus Drosophila, commonly known as "fruitflies," are good model systems for research in aging. Drosophila are extremely well-known genetically, developmentally, and otherwise. They are also genetically analogous to mammalian species in most important respects. Previous work with Drosophila has been hampered by inbreeding depression, but more recent work using selection has created Drosophila with postponed aging that is inherited normally. Genetic transformation has also increased Drosophila life spans in some cases. Several biologic approaches have been applied to the analysis of genetically postponed aging in Drosophila: quantitative genetics, organismal physiology, and protein electrophoresis. Ultimately, these different approaches will be integrated into an overall analysis of aging in Drosophila, one that could be valuable for research with other taxa as well.     

Free radical theory of aging.

Free radical reactions are ubiquitous in living things. Studies on the origin and evolution of life provide a reasonable explanation for the prominent presence of this unruly class of chemical reactions. These reactions have been implicated in aging. This phenomenon is the accumulation of changes responsible for the sequential alterations that accompany advancing age and the associated progressive increases in the chance of disease and death. Aging changes are attributed to the environment and disease, and to an inborn process, the aging process. The latter produces aging changes at an exponentially increasing rate with advancing age. Past improvements in general living conditions have decreased the chances for death so that they are now near limiting values in the developed countries. In these countries the intrinsic aging process is the major cause of disease and death after about age 28. The free radical theory of aging postulates that aging changes are caused by free radical reactions. The data supporting this theory indicate that average life expectancy at birth may be increased by 5 or more years, by nutritious low caloric diets supplemented with one or more free radical reaction inhibitors.     

Neuroendocrine mechanisms and aging.

Evidence describing altered neuroendocrine function during aging from this and other laboratories is reviewed, with focus on changes in the brain-pituitary-ovarian-adrenal-hepatic and in the brain-pituitary-ovarian systems. Difficulties in interpreting the discordant data on age-related changes in pituitary function are discussed. Among mechanisms of reproductive aging are changes at both the ovarian and hypothalamic level (including reduced catecholamine levels, turnover, and synaptosomal uptake). However, it cannot yet be concluded that impairments of hypothalamic catecholamine metabolism are the primary cause for the loss of regular cycles. Evidence for dopaminergic impairments in the basal ganglions of humans and rodents during normal aging suggests that these changes may be a general phenomenon of aging. Although the origins of the changes are not yet known, neuronal cell loss in the substantia nigra would not seem to be the only cause.     

Erythrocyte aging and malaria.

The human malaria parasite, Plasmodium falciparum, ages the red blood cell during its intracellular development. During this process of erythrocyte senescence the parasitized cell becomes less dense and deformable, its biconcave disc shape becomes more spherical and is covered with microscopic protuberances (knobs); the amounts of membrane cholesterol and phospholipids are altered and phosphatidylserine (PS) is externalized. The malaria-infected cell is osmotically fragile, more permeable to a wide variety of molecules via new permeation pathways (NPP), and there is surface deposition of immunoglobulins and complement. There are declines in sialic acid, reduced glutathione, tocopherol and ATP. Hemichromes are deposited on the inner surface of the red cell membrane and there is clustering of the anion transporter, band 3 protein, as well as exposure of neoantigens which contribute to antigenic variation and adhesivity of the parasitized erythrocyte. These time-dependent changes result from oxidative assault and a combination of factors, including a decline in levels of anti-oxidants and ATP coupled with an enhanced flux of ions especially calcium. Despite these parasite-induced age effects P. falciparum is able to avoid destruction by splenic removal through microvessel sequestration in the deep tissues via PS, clustered band 3 protein and adhesive neoantigens.     

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.     

Forecasting the obesity epidemic in the aging U.S. population

Objective: The objective was to forecast BMI distribution in the U.S. population along with demographic changes based on past race‐, sex‐, and birth cohort‐specific secular trends. Research Methods and Procedures: We compiled data from 44,184 subjects from 4 National Health and Nutrition Examination Surveys (NHANES; 1971 to 2004). By race and sex, we fit regression models to create smoothed mean BMI curves by age for 1970 to 2010. Linking corresponding birth cohorts across age‐ and year‐specific mean BMI projections, we estimated the trajectory of relative BMI throughout each cohort's lifetime. These projections were validated using actual cohorts in the Nurses’ Health Study and Health Professionals Follow‐up Study. Combined with U.S. census, we predicted BMI distributions in 2010 and examined the joint impact of the obesity epidemic and population aging. Results: BMI secular trends in the past 3 decades differ significantly by birth cohort, sex, and race. If these trends continue, the prevalence of obesity is expected to reach 35%, 36%, 33%, and 55% in 2010 among white men, white women, black men, and black women, respectively, far from the Healthy People 2010 goal of 15%. Such forecasts translate into 9.3 million more obese adults 20 to 74 years of age than in 2000, 8.3 million of whom would be 50 years of age or older, and 8.5 million of whom would be white. The mean age among obese men and women is also expected to rise from 47 to 49 years among whites and from 43 to 44 years among blacks. Discussion: As the baby boom generation approaches retirement age, the continuing obesity epidemic signals a likely expansion in the population with obesity‐related comorbidities. A framework to combine BMI and demographic trends is essential in evaluating the burden and disparity associated with the epidemic in the aging U.S. population.     

Problems in the aging of females using the Os pubis.

The Gilbert-McKern method for aging the female Os pubis has attained popularity following Gilbert's ('73) demonstration that the McKern-Stewart male standards are not directly applicable to females. In order to assess the reliability of the method, forensic anthropologists were asked to age a set of 11 pubes of known age. There was a great deal of variability in the responses of the 23 participants. Three, four, and five different responses (out of a 6-scale system) were given for each component of each pubic bone. Only 51% of the assessments yielded age ranges which would include the known age of the specimens. Analysis of the errors showed that one of the focal problems of the Gilbert-McKern system was the difficulty in judging whether the ventral rampart was building up or breaking down.     

Changes of the brain synapses during aging. New aspects

The process of brain aging is an interaction of age-related losses and compensatory mechanisms. This review is focused on the changes of the synaptic number and structure, their functional implications, regarding neurotransmission, as well as the electrical activity of neuronal circuits. Moreover, the importance of calcium homeostasis is strongly emphasized. It is also suggested that many neuronal properties are preserved, as a result of adaptive mechanisms, and that a series of interdependent factors regulate brain aging. The "new frontier" in research is the challenge of understanding the effects of aging, both to prevent degenerative diseases and reduce their consequences. New aspects are considered a) the role of nitric oxide, b) free radicals and apoptosis, c) impaired cerebral microcirculation, d) metabolic features of aging brain, e) the possible neuroprotective role of insulin-like growth factor-1 (IGF-1) and ovarian steroids and e) stress and aging. These numerous multifactorial approaches are essential to understand the process of aging. The more we learn about it, the more we realize how to achieve "successful" aging.