Age Related Diseases of the Human Retina

It is very common to encounter senile lesions of the eyes and therefore a reduction in the acuity of vision and also peripheral chorioretinal lesions, which cause severe retinal lesions such as senile retinal detachment. The interest in studying geriatric changes to vision lies in identifying the first lesions as early as possible. Not that it is possible, at least up to now, to impede the inexorable evolution of the degenerative phenomena, but an early diagnosis can at least allow us to...

Zebrafish as Aging Models

Zebrafish (Danio rerio) are well recognized as a powerful model for genetic studies in developmental biology. The zebrafish system has also given insights into several human diseases such as neurodegenerative, hematopoietic and cardiovascular diseases and cancer. The aging process affects these and various other human disorders, and it is important to compare age-related disfunctions at the organismal levels among vertebrates. From the point of view in comparative and evolutionary biology of...

The Honeybee Society

In contrast to the classic models of biological aging research, honeybees represent a species in an advanced state of social evolution. They live their entire lives as part of a complex society, the colony, and cannot survive or reproduce as solitary individuals. The honeybee society rivals traditional human societies in many societal parameters, such as group size, cohesiveness, information exchange, integration, and differentiation of roles (Wilson, 1980), including reproductive division of...

Table 561

Select biological alterations in tissues with slow turnover rate. (Adapted from Mooradian, A.D. (1988). J. Am Geriatr. Soc. 36, 831-839, with permission from the American Geriatrics Society and Blackwell Publishing.). NC No change Decrease Increase. Cognitive function Blood-brain barrier Transport of glucose, choline Transport of neutral amino acids NC NC Na K-ATP ase or Mg-ATP ase NC NC Endothelial barrier antigen Conjugated dienes Hormone stimulated adenylate cyclase activity Neurochemical...

References

Witter (1989). The three-dimensional organization of the hippocampal formation A review of anatomical data.'' Neuroscience 31(3) 571-591. Barnes, C.A. (1994). Normal aging Regionally specific changes in hippocampal synaptic transmission. Trends Neurosci 17(1) 13-18. Bozzao, A., R. Floris, et al. (2001). Diffusion and perfusion MR imaging in cases of Alzheimer's disease Correlations with cortical atrophy and lesion load.'' AJNR Am J Neuroradiol 22(6) 1030-1036. Braak, H.,...

Lh Levels And Aging

LH levels increase slightly with aging (Baker et al., 1976 Morley et al., 1997). Tenover and coworkers studied older men and noted that pituitary secretion of LH was intact, but testicular secretion of T was impaired in some older men (Tenover et al., 1987). They noted that the normal diurnal variation in T levels is blunted in aging men (Tenover et al., 1988). However, the majority of hypogonadal men over age 60 have low or inappropriately normal LH levels (Korenman et al., 1990). Older men...

Info

Gavrilova Mathematical models of systems failure are critically important for understanding the mechanisms of aging because aging of organisms is associated with increased risk of failure of its physiological systems. Theoretical analysis of systems failure in aging leads naturally to apply the existing general theory of systems failure, which is also known as the reliability theory. Reliability-theory approach to biological aging is useful for three reasons....

Glia Alterations

Glial cells are very numerous and in some parts of the brain they outnumber the nerve cells by 10 to 1. The well-known classification of this type of cells into astrocytes, oligodendrocytes, and microglia in addition to referring to their morphological features also categorizes their specific functions that include providing structural support for nerve cells, isolation and grouping of nerve fibers and terminals, participating in metabolic pathways that modulate the ions, transmitters, and...

Conducting Research For The Good Of Elderly Persons

The principle of beneficence requires that investigators maximize benefit and minimize harm to human research subjects. This principle also demands that investigators protect subjects from exploitation. Indeed, the Belmont Report states that ''the appropriateness of involving vulnerable populations in research should be demonstrated'' (The Belmont Report, 1979). Elders, especially those with diminished cognition and living in nursing homes or other institutions, are vulnerable to exploitation...

Analytical Epidemiology

The aim of analytical epidemiology is to identify risk factors or protective factors for diseases and functional impairments, and to quantify their impact on disease (or functional impairment) occurrence by measures such as the relative risk, the risk difference or more recently developed measures which may be particularly relevant for aging research, such as risk advancement periods (Brenner et al., 1993). In the simplest case of a binary exposure and a binary outcome (disease), the data...

Selection Of Modern And Classic Textbooks In Epidemiology

Epidemiology. (4th ed.). Saunders, Philadelphia. Kleinbaum, D.G., Kupper, L.L., and Morgenstern, H. (1982). Epidemiologic Research. John Wiley and Sons, New York. Last, J.M. (2001). A Dictionary of Epidemiology. (4th ed.). Oxford University Press, New York, Oxford. Lilienfeld, D.E., and Stolley, P.D. (1994). Foundations of Epidemiology. (3rd ed.) Oxford University Press, New York, Oxford. Rothman, K.J., and Greenland, S. (1998). Modern Epidemiology. (2nd ed.) Lippincott-Raven...

Nutritional Programming

This topic is most often raised in response to the question ''What if any are the fetal origins of individual differences in aging and the incidence of age-related diseases '' During pregnancy, dietary requirements change because a mother must consume or synthesize all that is required for the growth and development of her baby. Factors like poverty, moral or religious taboos, or poor education are major influences on dietary habits in pregnancy. If, for reason of poor diet or placental...

MtDna Replication

To balance the loss of mtDNA molecules by degradation, mtDNA must be continually copied. This replication is independent of the cell cycle, and occurs in all cells, including postmitotic cells. The total number of mtDNA molecules replicated, ncopy, in a time span At must be equal to the mean number lost to degradation plus any additional growth, ngrow, which would be needed in dividing cells. ncopy nd) + ngrow N(ln(2)At Thaif) + ngmw (4) Little is known about the control of the mtDNA...

Caspase Regulation

Caspase-3 is markedly activated after HI in the immature rat brain (Zhu et al., 2000 Wang et al., 2001 Benjelloun et al., 2003) compared to ischemia in the adult brain (Namura et al., 1998). In P7 rat brain, caspase-3 activation contributes substantially to cell death after ischemia with reperfusion not only in the penumbra but also in the core (Benjelloun et al., 2003 Manabat et al., 2003), and cells with the cleaved active form of caspase-3 colocalize with markers of DNA fragmentation in...

Basic mtDNA Biology

Human mtDNA is a circular double-stranded molecule that is 16,569 bp long (other sequenced mammalian mitochondrial genomes have similar lengths see Figure 41.1). It carries 37 genes, of which two encode rRNAs, 22 encode tRNAs, and 13 encode polypeptides. All 13 mitochondrially encoded polypeptides represent components of the electron transfer chain (ETC). Of these, seven are subunits of complex I (NADH dehydrogenase), three are subunits of complex IV (cytochrome c oxidase), two are subunits of...

Apoptotic Protein Activation Following Cerebral Ischemia Newborn versus Adult

It is now well accepted that immature neurons may be more prone to apoptotic death, whereas terminally differentiated neurons exhibit pyknosis or die by necrosis. Both neuronal apoptosis and necrosis have repeatedly been observed in neonatal HI (Pulera et al., 1998 Renolleau et al., 1998 Nakajima et al., 2000), whereas neuronal degeneration in the adult cerebral nervous system exists as a continuum between apoptosis and necrosis (Charriaut-Marlangue et al., 1996a Liu et al., 2004). This...

Aging of the Whole Retina Experimental Results

In our experiments, only samples of the retinas coming from living humans and not from autopsies were used because post-mortem phenomena may bring about early modifications in the morphometric data obtained from the retinas. Our studies were approved by the local Ethical Committee, and patients or their relatives gave their informed written consent. The investigations were performed according to the guidelines of the Declaration of Helsinki. After removal, the eye-bulb was dissected with a...

Aging and the Perceptual Organization of Sounds A Change of Scene

Dyson, and Joel S. Snyder The peripheral and central auditory systems undergo tremendous changes with normal aging. In this review, we focus on the effects of age on processing complex acoustic signals (such as speech and music) amid other sounds, which requires a set of computations known as auditory scene analysis. Auditory scene analysis is the process whereby the brain assigns parts of the acoustic wave derived from an amalgamation of physical sound sources into...

Table

Useful Web-based resources for investigators engaged in research involving elderly persons 1. The World Medical Association Declaration of Helsinki http www.wma.net e7policy b3.htm 2. Belmont Report 3. Common Rule 4. American Geriatrics Society ''The Responsible Conduct of Research'' 5. American College of Physicians Ethics Manual, 5th edition 6. American Psychiatric Association ''Guidelines for Assessing Decision-Making Capacities of Potential Research Subjects with Cognitive Impairment'' 7....

Table 601

Changes in structure and function of the aging human respiratory system Structural disruption and possible loss of elastin Altered cross-linking of elastin and collagen Loss of alveolar surface area Enlargement of terminal airspaces Decreased number of capillaries per alveolus Decreased diameter of small bronchioles Increased interalveolar pores (pores of Kohn) Other respiratory system changes Decreased chest wall compliance Decline in respiratory muscle function Changes in measures of lung...

Neurophysiological Resistance

Bats exhibit an unusual ability to tolerate potentially ischemic conditions in both the cardiovascular and neurophysiological systems during arousal from hibernation and or daily torpor. Lee et al. (2002) reported that oxygen consumption during arousal thermogenesis increased from near zero to 11.9 ml kg h. They also reported a rise in body temperature from 7 to 35 Celsius, suggesting potentially ischemic conditions in the heart, brain and other vital organs and tissues. Glucose related...

Musculoskeletal Disorders

Musculoskeletal disorders represent another group of diseases whose incidence steeply increases with age and which are rarely fatal by themselves, but which account for a major share of detriments in quality of life, disability and costs for medical and nursing care among older adults. Up to 10 of cases of severe disability are mainly caused by these disorders (Ramroth et al., 2005). The most important disabling musculoskeletal disorders include osteoporosis and osteoarthrits. The former is the...

Longer Life Expectancy In Organisms Belonging To The Same Cohort Group Is Associated With Relatively Higher Levels Of

All houseflies lose the ability to fly prior to death. Therefore, in an aging population, shorter-lived flies can be identified as flightless crawlers in contrast to their longer-lived cohorts, the fliers. The average lifespan of crawlers is about one-third shorter than the fliers. Levels of antioxidant defenses (superoxide dismutase (SOD), catalase (CAT), and glutathione) and products of oxygen free radical reactions (inorganic peroxides and thiobarbituric acid TBA -reactants) were compared...

Compare Percentiles

An alternative approach is to compare percentiles or quantiles across groups. Quantile regression is such an approach (Koenker and Bassett, 1978). It is used to estimate conditional quantile functions by minimizing the weighted sum function. Redden et al. (2004) recently developed a simplified quantile regression method using logistic regression which has an appropriate type I error rate and good power. For comparing maximum lifespan, one needs to first find the 90th percentile for all animals...

Collecting Virgin Females

Female Drosophila store sperm after mating and are capable of laying fertile eggs for many days. Therefore in order to set up a cross between males and females of known genotypes, it is essential to collect virgin females. To do this, in the morning, empty all the flies from bottles that have adult flies just emerging from pupae. Then collect flies that eclose over the next 8 hours and separate into sexes. Virgins have dark meconium in the gut, visible through the ventral abdominal wall. Virgin...

Beneficence

The Hippocratic maxim ''First, do no harm'' is important but not sufficient to guide the ethics of research. The risk of harm must be compared with the potential benefits, through a form of cost-benefit analysis which takes place on three levels for the sake of the individual research subject, for all those affected by the protocol, and for society-at-large. Good research design and execution are ethical, insofar as they minimize harm and maximize benefit. The metaphor of ''balancing'' risks...

Aging of the Macroglia Mller Cells and Astrocytes

The functional weakening of the CNS that occurs with aging and age-related neurodegenerative disorders has been partially attributed to a decline in mitochondrial function. In particular, it has been demonstrated that oxidative damage occurs to mitochondrial DNA in elderly human brains. Recently, it has been shown that mito-chondrial DNA is particularly sensitive to damage that accumulates due to the loss of protective histones, the reduction in repair systems, and the vicinity of the internal...

Bats as a Novel Model for Aging Research

Rossinni Despite small body size and high metabolic rate, bats are exceptionally long-lived mammals. This longevity, the ecological, behavioral and morphological diversity, and the unique life history traits of this multispecied order of mammals make bats well-suited as model systems for aging research. Including bats in comparative investigations may provide insight into universal mechanisms of senescence as well as reveal mechanisms that confer resistance...

Plasma Leptin

Plasma leptin concentrations are known to reflect body fat content (Niswender and Schwartz, 2003). At the age between 6 and 8 months, plasma concentrations did not significantly differ among rat groups, although the fat content was slightly lower in (tg tg) rats compared with Figure 31.5. (A) Body fat content, and (B) plasma leptin and (C) adiponectin concentrations. The body fat content represents the combined wet weights of perirenal and epididymal fat normalized by body weight (g 100 g body...

General Characteristics and Life History Traits of the Order Chiroptera

With over 1100 species of bats worldwide, the order Chiroptera is the second most multispecied among mammals, accounting for almost one-fourth of all mammalian species. The order is divided into two suborders. The Megachiroptera is a group of just under 200 species, which includes the flying foxes and fruit bats of the Old World. The Microchiroptera with over 900 species includes all the bats of the New World and some Old World species. The two suborders differ in sensory and feeding...

F344bnf1

Different parental alleles at many loci produces the pay-off of improved health. Tables 33.1 and 33.2 compare the median lifespan and the average maximum body weight of some of the inbred and hybrid mouse and rat strains included in the NIA's aged rodent colonies. Genetically heterozygous (HET) mice are another alternative to inbred strains. HET mice are mixtures of four (F2 generation) or eight (F3 generation) strains of mice. They have more genetic diversity, with individuals in the...

Aging Of The Reproductive System In Females

The rhesus monkey (Macaca mulatta) has been a biomedical model for reproductive studies in women since the early 1900s (Heape, 1900). Female rhesus monkeys are pubertal by 2.5 to 3.5 years of age and exhibit menstrual cycles approximately 28 days in length, similar to humans. Furthermore, rhesus monkeys experience a reproductive decline much like that of human menopause around 24 years (Gilardi et al., 1997 Bellino and Wise, 2003). Urinary hormone profiles demonstrated that, like women,...

Recommended Links

Sleep disorders in the elderly. 000064.htm visualContent Describes the normal sleep and its aging, and common sleep disorders and their treatment. UniversityAlliance. Sleep Disorders of the Elderly American Academy of Family Physicians Management of Sleep Disorders in the Elderly. Veterans Affairs Canada. steannes pub_research bgroulx_04

Osteoporosis

One of the common degenerative diseases of aging is osteoporosis. Bone density is decreased in an age-dependent fashion after it reaches its peak at young adulthood. The prevalence of osteoporosis and fractures increases with age. In women, estrogen withdrawal accompanying menopause plays a major role in the first 10 years. Diabetes also is associated with increased risk of fracture of the hip, proximal humerus, and foot (Inzerillo and Epstein, 2004 Schwartz, 2003). Type 1 diabetes is...

Frequency Of Chromosome Errors In Primates

It is well established that aneuploidy is common in human oocytes and IVF embryos, and that the frequency of these anomalies increases with age, especially after age 25 (Munne and Cohen, 1998 Munne et al., 2002). Several studies have reported frequencies up to 50 for aneuploidy (Gras et al., 1992) and as high as 48 for mosaicism (Munne et al., 2002). In the latter study, as many as 84 of cells in ''chaotic mosaic'' embryos were abnormal. However, all the data are from oocytes and IVP embryos of...

Stem Cells Of The Spleen

Diabetes is an insulin insufficiency disease that affects over 6 of the U.S. population. People with diabetes are at higher risk for heart disease, blindness, kidney failure, and other chronic conditions. Diabetes cost the United States an estimated 132 billion in 2002 in direct medical and indirect expenditures (Hogan et al., 2003). Pancreatic -cell death directly leads to Type I diabetes, causing a misregulation of glucose homeostasis. Patients with Type I, insulin-dependent diabetes require...

What Are the Limitations to Place Cell Research

Single-cell recordings allow the study of information processing by individual neurons of a particular region within the brain with enough temporal precision to correlate activity of individual neurons with particular behaviors. The power of single-cell recordings is limited, however, by the facts that the electrodes sample a very small selection of the neurons from only one subregion of the brain, monitoring numerous brain regions simultaneously is difficult (but see Lee et al., 2004), and the...

Schema Driven and Attention Dependent Processes

Current models of auditory scene analysis postulate both low-level automatic processes and higher-level controlled or schema-based processes (Alain and Arnott, 2000 Bregman, 1990) in forming an accurate representation of the incoming acoustic wave. Whereas automatic processes use basic stimulus properties such as frequency, location, and time to segregate the incoming sounds, controlled processes use previously learned criteria to group the acoustic input into meaningful sources and hence...

Aging Research on Bats

Few studies have examined bat longevity, and due to continually improving lifespan data, it is not surprising that some of these studies have reached contradictory conclusions. Some of the earliest work that considered the question of why bats live so long was a comparative survey of lifespans by Bourliere (1958). Addressing the question from the standpoint of the rate of living theory (Pearl, 1928 Sacher, 1959), Bourliere described the extreme longevity of bats as a simple consequence of...

Zebrafish Model Of Ataxia Telangiectasia

A-T is an autosomal recessive disorder characterized by progressive cerebellar degeneration, immunodeficiency, cancer predisposition, gonadal atrophy, growth retardation, premature aging, and hypersensitivity to IR (Lavin and Shiloh, 1997 McKinnon, 2004). Cells from A-T patients generally have short telomeres and are also highly sensitive to IR (Kishi and Lu, 2002 Metcalfe, et al., 1996 Meyn, 1995 Pandita et al., 1995 Shiloh, 1995 Smilenov et al., 1997). The molecular cloning of the gene...

Health Precautions For Researchers Handling Bats

Rabies is a significant concern for researchers handling bats, not because bats exhibit a higher incidence of rabies infection than other wild mammals, but because without prompt treatment rabies is nearly always fatal in humans. The virus is most commonly transmitted via contact with infected saliva through a bite, but other means of transmission include contact of infected saliva and nervous tissue with mucous membranes of the mouth, nose and eyes. There have also been two cases of...

The Simplest Reliability Model Of Aging

In this section we show that a system built of nonaging components demonstrates an aging behavior (mortality growth with age) and subsequent mortality leveling-off. Consider a parallel system built of n nonaging elements with a constant failure rate and reliability (survival) function e- x (see also Figure 5.3b). We already showed (see the system's failure and reliability structure section) that in this case the reliability function of the entire parallel system is This formula corresponds to...

Life Course Approach

Life course epidemiology studies the long-term effects on later health- or disease-risk of physical or social exposures during gestation, childhood, adolescence, young adulthood, and later adult life (Kuh et al., 2003). It allows the integration of biological, behavioral, clinical, psychological, and social processes that interact across a person's life (Ben-Shlomo et al., 2002). This is not a new concept in aging research. Over 50 years ago Nathan Shock wrote, ''In the broadest sense, problems...

Muscle Biopsy

The use of percutaneous muscle biopsy represents one of the few ways in which the effects of aging on human muscles can be studied at the biochemical, molecular, or cellular level. A single biopsy can yield 25 to 75 milligrams of tissue, which can then be analyzed in multiple ways including via microscopy or biochemical assays (Coggan, 1995). Muscle biopsy involves the use of a biopsy needle, such as the one developed by Bergstrom, which consists of a closed hollow cylinder with a pointed tip...

Aging And Longevity Of Species

Reference conditions An involvement of the molecular chaperones in the definition of species longevity can be assumed from the observed influences of genotypes, levels of Hsp expression, and mutational defects. Thus, a modifier of life span linked to chromosome 4 has been identified as a haplotype marker within the microsomal transfer protein complex comprising the chaperone protein disulfide isomerase (PDI). An influence of genotype can be supposed also from the observation that for Hsp70 the...

Tests of Cognitive Function and Brain Regions Important for Cognitive Function

One of the most controversial issues pertaining to management of the perimenopausal transition is that of neuroprotection and maintenance of cognitive function. The rhesus macaque provides a highly useful model for performing tasks that provide specific information on neural systems. This allows for characterization of age-related changes in cognitive function with females during the perimenopausal transition and with surgical removal of ovarian steroids. Moreover, selected interventions may be...

Sclerodermalike Skin Changes

Skin changes were first clearly described in the patient series reported by Thannhauser, who distinguished changes in WS patients from those commonly seen in scleroderma patients or in patients with RothmundThomson syndrome (Thannhauser, 1945). The histologic appearance of skin biopsies from WS patients reveals an interesting mix of atrophic and proliferative changes. There is epidermal atrophy that extends to include skin appendages (e.g., hair follicles, sweat and sebaceous glands), in...

Cones And Rods

The acromeres of the cones and the rods become disorganized, and the internal segments fill with refractant bodies, presumably lipofuscin. The dislocation and partial loss of photoreceptor nuclei happens without significant modifications to the RPE, the Bruch's membrane, and the choriocapillaries (Curcio et al., 1993). Gao and Hollyfield (1992) suggest that the loss of rods begins early in adult life, and the density of cones diminishes gradually in the extreme retinal periphery. On the...

Role Of Genes

Saying that the frailty phenotype arises from geneenvironment interactions doesn't move us very far forward as these interactions are pervasive throughout biology. Nonetheless, the emerging work on the genetics of aging, age-associated diseases, and age-associated functional decline will become increasingly relevant to our understanding of frailty (Johnson et al., 1996 Hamet et al., 2003 Gurland et al., 2004 Martin 2005 Hadley et al., 2005). Although genes likely influence the development of...

Auditory Scene Analysis

The root of the auditory scene analysis problem is derived from the inherent complexity of our everyday acoustic environment. At any given moment, we may be surrounded by multiple sound-generating elements such as a radio playing music, or a group of people speaking, with several of these elements producing acoustic energy simultaneously. In order to make sense of the environment, we must parse the incoming acoustic waveform into separate mental representations called auditory objects or, if...

Role Of The Social Environment As People

Gerontological research on social environments is seeking to identify in what ways qualitative as well as quantitative features of an individual's social contacts and social network contribute to the individual's functioning and life quality (Lang and Carstensen, 1998 Pinquart and Sorenson, 2000 Rook, 2000). The theoretical conceptions about the role of social environments across adulthood are manifold and range from macro-theoretical approaches such as the age stratification theory (Riley,...

Aging and Replicative Senescence

Cellular or replicative senescence (in vitro) is often utilized as a model for the aging process (in vivo) due to the hypothesis that cellular aging recapitulates organismal aging (Wadhwa et al., 2005). The central dogma of repli-cative senescence holds that cultures of vertebrate fibroblasts have a limited capacity for proliferation. After a finite number of cell divisions, proliferation slows and culture arrest ensues. The barrier represented by culture arrest, termed the Hayflick Limit, is...

Introduction

Life expectancy has increased markedly during the last century, which resulted in the augmentation of the elderly population. Among this elderly population the proportion of those over 85 years has increased even more dramatically. This phenomenon is accompanied by the enhancement of the incidence and prevalence of age-related diseases. The most common age-related diseases are infections, cancers, cardiovascular diseases and type 2 diabetes mellitus. Data from the epidemiological studies show...

Models of Immune Function in Aging

The most prevalent rodent models used in aging research are relatively healthy long-lived rats and mice and shortlived mice. The short-lived mice typically spontaneously develop a particular disease or are genetically altered. This review focuses on the most prevalent disease model, the autoimmune-prone mouse, to study the impact of diet on aging. The benefit of these mice is that their life span is half that of the long-lived strains, allowing for data to be generated faster. Specifically,...

Mouse Models of Accelerated Aging

Mouse mutants displaying aging phenotypes much earlier in time than normal control animals offer the opportunity to develop and test interventions to reduce aging-related morbidity and mortality in humans. However, the few natural mouse mutants identified in the past as accelerated aging models have been criticized as less suitable for studying mechanisms ofnormal aging because neither the nature of the mutational defect nor the genetic background was accurately defined. A more general critique...

Developing Highthroughput Methodologies For Lifespan Analysis

Until recently, discovery of genetic and environmental determinants of longevity in any organism has been driven largely by gene-specific studies based on prior knowledge or hypotheses. The development of new methods and technologies for moderate to high-throughput longevity phenotyping in yeast offers the promise of analyzing the replicative and chronological aging properties of thousands of strains simultaneously (see Chapter 10 Application of High-Throughput Technologies to Aging-Related...

Experimental Animal Models

Currently there exist several experimental animal models for the study of diabetes (Mathews, 2002). The most currently used are from rodents. All these animal models mainly reproduce by genetic engineering single specific alterations found in type 2 diabetes. These models try to elucidate one particular pathological aspect of the disease. The most widely used are the leptin-deficient ob ob_ mice, db db+ + mice, KATp-channel mutated, ApoE deficient mice with other deficiencies, several knock-out...

Methods for the Study of Bats

WILD BAT POPULATIONS MONITORING AND CATCHING Bat roost selection varies considerably they will roost in caves, mines, occupied and unoccupied buildings, trees, under leaves, under bark, under rocks and in cliff crevices (Kunz, 1982). Usually, roosts occupied by colonial species are easier to find because of the number of bats present and because some of these species exhibit high fidelity to their roosts. This is especially the case for species that form nursery colonies, as roosts that provide...

Sensitivity Of Respiratory Centers And Clinical Symptoms

Lower sensitivity of respiratory centers to hypoxia or hypercapnia in older subjects results in a diminished venti-latory response in case of acute disease such as heart failure, infection, or airway obstruction, and thus delays important clinical symptoms and signs such as dyspnea and tachypnea, which are important for the diagnosis of pneumonia and appreciation of its severity (Kronenberg et al., 1973 Peterson et al., 1981). Aging is also associated with a decreased perception of added...

Animal Models Of Macular Degeneration

Limited access to appropriate biological materials, especially eye samples from affected donors at different stages of the disease, are an absolute necessity to study mechanisms underlying the macular degenerations. Because it is nearly impossible to obtain these human retinal tissues from patients or from normal controls, animal models play a crucial role for investigating the biological pathway of disease development and for testing therapeutic strategies. Because age-related macular...

Bone Marrow Stem Cells

The vast majority of bone mass is achieved in the human adult by the age of 18, with a small amount accumulated up to the age of 30. In a healthy adult, bone remodeling is a balance between bone resorption, via osteoclasts, and bone formation, by osteoblasts. Changes in levels of endogenous hormone and mechanical load, due to age-related changes in physical activity, determine the extent of bone remodeling. The prospect of bone repair and prevention Reduced activity of osteoblasts observed with...

Ischemia Of The Inner Retina

Ischemia of the inner retina, caused by the presence of naked or acellular vessels (formed from a thickening of the basal membrane of the capillaries), will be aggravated by the difficulty of diffusion of nutrients across the inner limiting membrane, and the elimination of catabolites. In the group of people with AMD, the changes are more severe than those in normal individuals of the same age. The changes to the inner retina in individuals with AMD are equivalent to those of the outer retina...

Genetic Models Of Hypertension

Spontaneously hypertensive rat (SHR) Males. The SHR is a commonly used model of hypertension (Reckelhoff, 2001). These animals develop increases in blood pressure beginning at six to seven weeks of age and reach a stable level of hypertension by 17 to 19 weeks of age. Inhibitors of the renin-angiotensin system reduce blood pressure in SHR, suggesting a role for the RAS in mediating the hypertension. Removal of the renal nerves also reduces blood pressure in SHR, suggesting that the sympathetic...

Animal Models Of Poag

Overview Difficulty of modeling the human eye Limited access to appropriate biological materials, especially eye samples from affected donors at different stages of the POAG, is an impediment to the study of mechanisms underlying the disease. Because of the extreme difficulty in obtaining such diseased eyes from both patients and normal controls, animal models play a crucial role in investigating the biological pathway of disease development and in testing therapeutic strategies. Different...

Failure Laws In Survival Studies

Attempts to develop a fundamental quantitative theory of aging, mortality, and lifespan have deep historical roots. In 1825, the British actuary Benjamin Gompertz discovered a law of mortality (Gompertz, 1825), known today as the Gompertz law (Finch, 1990 Gavrilov and Gavrilova, 1991 Olshansky and Carnes, 1997 Strehler, 1978). Specifically, he found that the force of mortality increases in geometrical progression with the age of adult humans. According to the Gompertz law, human mortality rates...

Age Related Hippocampa Dysfunction Early Alzheimers Disease vs Normal Aging

As we age, all of us will experience an inexorable slide into forgetfulness. Age-related memory decline localizes, in part, to the hippocampal formation, a brain circuit made up of separate but interconnected hippocampal subregions. Human studies have established that Alzheimer's disease targets the hippocampal circuit early in its course, and since Alzheimer's disease affects older individuals it is one cause of age-related hippocampal dysfunction. Animal studies, however, have established...

Relationship between Replicative and Chronological Aging

Cells that have been maintained in stationary phase for a sufficient length of time (chronologically aged) demonstrate reduced replicative capacity (Ashrafi et al., 1999), suggesting that chronological and replicative aging are linked in some way. This link appears to be unrelated to ERCs, as chronologically aged cells do not have a detectable increase in ERC levels relative to young cells (Ashrafi et al., 1999). One attractive hypothesis is that accumulation of oxidatively damaged proteins...

Highthroughput Longevity Phenotyping

Alternatives to standard life-span assays that accelerate the normal aging process can be useful tools for rapidly screening genes and compounds for effects on longevity. These methods suffer, however, from the fact that they are not true aging assays and putative aging effects must be verified in each case. A more satisfying, but also more difficult approach, is the development of automated, high-throughput methods for standard life-span measurements. The system most amenable to...

Atherosclerotic

Figure 72.1 Swine model of atherosclerosis. Histologic samples from normal and atherosclerotic pig arteries demonstrate the hallmark characteristics of atherosclerosis, including cholesterol deposition, calcification, foam cell accumulation, and development of a fibrous cap. Figure 72.1 Swine model of atherosclerosis. Histologic samples from normal and atherosclerotic pig arteries demonstrate the hallmark characteristics of atherosclerosis, including cholesterol deposition, calcification, foam...

Cytogenetic Analysis Of Rhesus Macaque Oocytes And Embryos

Aneuploidy analysis can be done in two ways. First, standard karyotyping analysis can be performed on metaphase II oocytes exhibiting a first polar body. Karyotyping was previously used to examine age-related defects in rhesus monkey oocytes (Schramm et al., 2002). In that study, no statistically significant difference was found between young vs. old rhesus monkeys in aneuploidy frequency of oocytes. However, the number of oocytes examined was very small, totaling only 30 oocytes for both...

Glucose Tolerance

At a young age, time-dependent alterations in blood glucose in the glucose tolerance test (GTT) were similar among ( ), (tg ), and (tg tg) rats when fed ad libitum (Figure 31.3A). In ( ) rats, aging impaired glucose tolerance, particularly in the AL group (Figure 31.3B) in the CR group, it was mostly inhibited. In (tg ) rats, glucose intolerance was also observed in the AL group at old age (Figure 31.3C) CR inhibited aging-related impairment. In (tg tg) rats, time-dependent changes in blood...

Domestic and Wild Bird Models for the Study of Aging

Comparative gerontologists now recognize that birds as a group are exceptionally long-lived for their body sizes, especially given their lifetime energy expenditures, and that domestic and wild avian models hold significant potential for understanding basic aging processes. Some domestic birds, including chickens, pigeons, quail and small cage bird species, are actually already well developed as laboratory models, and have been used for years in studies of neurobiology, reproductive biology,...

Technical Challenges and Advances What Are Tetrodes and Microdrives

Action potentials of single cells are recorded by bringing small-diameter wires close to the soma of neurons (see Figure 37.1). Because the pyramidal cells of the hippocampus are so tightly packed, a single 13-micron diameter electrode will detect action potentials from many neurons. This is good, except that with a single electrode, one cannot differentiate action potentials from individual neurons. To solve this problem, hippocampal researchers twist several electrodes together into a tetrode...

Methods of Age Determination in Bats

Bats are difficult to age once they reach adulthood, and the currently available methods of age determination have several limitations. To begin with, bats show no visible markers of aging, and the few traits that have been correlated with age to establish reference standards show significant variation due to genetic structuring of populations and environmental variation which impacts development. Additionally, available reference standards lack data from very old bats, likely because the...

Co

The values in Table 3.1 were calculated as follows The cost of a 3-month-old mouse is estimated as 7. The cost per month thereafter is calculated as 7 times the number of mice alive at the start of the month. The colony size is 1000 mice initially. It is assumed that no mice die until age 12 months. Mortality rate doubling time is taken as 0.3 years. The risk of death in any given month (after age 12 months) is calculated as m(t) 0.01 * exp(2.31 * f 12), where t (number of months of age 12)....

Inbred Strains

One of the most important considerations in choosing a rodent model is the genetic background. There are advantages and disadvantages of different genetic backgrounds that must be weighed equally. Inbred strains have the advantage that all individuals of the strain are genetically identical, providing a uniform population for study. Small sample sizes are sufficient for most studies because of the genetic homogeneity. Care must be taken to note the substrain being used, as there can be genetic...

Microsatellite Instability

The influence of DNA repair capacity on genomic integrity is suggested by the positive correlation between life span and DNA repair capacity and evidenced by progeroid syndromes in which DNA repair defects can cause phenotypes resembling premature aging (Lombard et al., 2005). The accurate maintenance of nuclear DNA is critical to cell and organism functions, and therefore numerous DNA repair pathways have evolved for the different types of DNA lesions. Among these pathways, the nucleotide...

Consideration of Zebrafish as Models for Aging

Since its introduction by Streisinger, the zebrafish has become a popular genetic model for studying development and disease because of its many advantages (Jagadeeswaran et al., 2005 Streisinger et al., 1981). One advantage is that zebrafish embryos are transparent, so a developing embryo and its morphology could be easily observed. Breeding zebrafish under laboratory conditions is extremely easy the embryos grow for 72 hours until they hatch. Other advantages include high fecundity (the...

Zebrafish And Hsps

A variety of heat shock proteins and the heat shock transcription factor Hsf1 have been identified and cloned from zebrafish (Krone et al., 1994 Graser et al., 1996 Lele et al., 1997b Santacruz et al., 1997 Rabergh et al., 2000). Many of these heat shock genes exhibit complex patterns of constitutive and inducible expression during embryonic development (Krone et al., 1997). For example, the Hsp90alpha gene is expressed at low levels constitutively but is strongly upregulated during heat shock,...

Allostatic Load And Hormesis

The concepts of allostasis and hormesis deal with the relationship between an organism and its environment. They may have particular relevance to frailty and could explain how early life events could have late-life consequences. Allostasis (literally meaning ''achieving stability through change'') is a dynamic regulatory process that allows the organism to adapt to the challenges of its environment. It is an extension of the concept of homeo-stasis (the ability or tendency of an organism or a...

Atherosclerosis

Atheroma is the term used to define the caseous material, containing high amounts of lipids, found in plaque-like thickenings of the interior portion of the vessel wall. Accordingly, the term atherosclerosis reflects the fibrous character of these pathologic alterations affecting large and small peripheral arteries in aging. Atherosclerosis begins as a disease of the innermost layer of the vessel wall the intima , where the main lesions responsible for its development have been categorized as...

Benign Prostatic Hyperplasia

Luts Increase With Age

Benign prostatic hyperplasia is a common disease of aged males. It is associated with low urinary tract syndrome and can result in serious complications including renal failure. The main pathophysiological factors, and consequently, therapeutic targets, are sex hormones and sympathetic activity. Testosterone, dihydrotestosterone, and estradiol play crucial roles, and their effects are influenced by several genetic factors. The models of benign prostatic hyperplasia can be divided into in vivo...

Cancer In Werner Syndrome

WS patients are at increased risk of developing cancer Goto et al., 1996 Monnat, 2001 Monnat, 2002 . The elevated risk of neoplasia in WS patients is of particular biological interest. As discussed later, neoplasia may be an expression of important mechanistic links between WRN function in vivo, genome stability assurance, and the limitation of cell proliferation defects. The elevated risk of neoplasia in WS is selective in that only a small subset of neoplasms are clearly elevated in incidence...

Nonhuman Primate Models Old World Monkeys

Nonhuman primates NHP are classified as Old World monkeys, New World monkeys, and Great Apes. The Old World monkeys OWM are most commonly used in biomedical research, and, of these, the Asian macaques and the baboons of Africa are most frequently used. OWMs have a genetic makeup approximately 92.5 to 95 similar to humans and undergo similar reproductive processes as humans. The NHP reproductive cycle is approximately 28 to 30 days, with a follicular, prolif-erative, and luteal phase that...

Atherosclerosis and Aging

There are two explanations for the increased prevalence of vascular disease in the elderly 1 the increased risk represents a longer duration of exposure to conditions that promote atherosclerosis i.e., the time-dose product of the risk factors and 2 atherosclerosis is a specific aging-associated process. It is important to note that these possibilities are not mutually exclusive and that from the perspective of a given elderly individual at risk for vascular disease, this distinction may not...

Bacterial Pneumonia

In recent clinical studies of older patients with either CAP or NHAP, the most frequently identified microorganisms were S. pneumoniae, H. Influenzae, Enterobacteriacae, and S. aureus. S. pneumoniae is by far the predominant pathogen isolated in hospital-based studies of elderly patients with either CAP up to 58 or NHAP up to 30 Riquelme et al., 1996 Lieberman et al., 1997 Marrie et al., 1997 Riquelme et al., 1997 Lim et al., 2001 Kaplan et al., 2002 Zalacain et al., 2003 . In older subjects...

Hemorrhagic Stroke Model

Several animal models of intracerebral hemorrhage ICH have been developed in mice, rats, rabbits, cats, and nonhuman primates. A widely used method that produces ICH by injection of bacterial collagenase into the basal ganglia was first introduced in the rat and was subsequently studied in the mouse Rosenberg et al., 1990 Clark et al., 1998 . This enzyme digests the collagen present in the basal lamina of blood vessels and causes bleeding into the surrounding brain tissue. However, another...

Immune Surveillance And Susceptibility To Infection

Respiratory infections are recognized as the fifth leading cause of death for individuals over age 65 National Vital Statistics, 2001 . There are many factors that make the elderly more susceptible to lung infections. These include declining immune function, impaired oral and mucociliary clearance, neurologic disorders, malnutrition, chronic organ dysfunction syndromes, and the presence of parenchymal lung disease Meyer, 2004 . Although various aspects of systemic immunity decline with...

The Replicative Lifespan Assay

The goal of the replicative life-span assay is to determine how many times each mother cell buds before senescence. Cell division in yeast is an asymmetric budding process resulting in the production of a larger mother cell and a smaller daughter cell. The mother and daughter cells can be easily differentiated by an experienced researcher using a standard light microscope total magnification 160 x such as the Zeiss Axioscope 40 or another comparable model. Physical separation of daughter cells...

Neonatal Models Of Stroke

Neonatal Stroke

These models generally require a permanent occlusion of one of the two major cerebral arteries in association with a transient occlusion of the other one to produce low cerebral blood flow, because of the presence of the Circle of Willis. In the Renolleau model Renolleau et al., 1998 see Figure 42.1B , anaesthetized rats were positioned on their backs, and a median incision was made in the neck to expose the left common carotid artery. Rats were then placed on the right side, and an oblique...

Aging Of The Functional Morphology Of The Bruchs Membrane

Investigations have shown that the areas of reduced perfusion have an elevated threshold of adaptation to the dark and a pattern of changes similar to those observed in cases of Vitamin A deficiency. The second group of studies arrived at the same conclusions by demonstrating that Sorsby's dystrophy, an illness that causes loss of central vision at a young age, is characterized by the presence of rich deposits of lipids in the Bruch's membrane. The conclusion of these studies is that the loss...

Depression in Older Patients

Major depressive disorder is frequently undiagnosed and untreated in older patients, and can be associated with high morbidity and mortality in this patient group, who are particularly prone to completed suicide or self-neglect. Grief, pain, sleep issues, concurrent medications, altered physiology, and the presence of comorbid medical and psychiatric conditions can complicate the management of depression in older patients. Comorbid medical conditions, including cardiovascular events, stroke,...

Animal Models Of Agerelated Cataracts

Since cataractogenesis is a complex process accompanied by numerous secondary changes, animal models may provide useful information for delineating the causes of senescent and other cataracts. Hereditary cataracts in rodents have been especially useful in this regard Graw and Loster, 2003 . One example is the Philly mouse, which displays an autosomal dominant cataract in which there is a deficiency of B2-crystallin polypeptide. The B2-crystallin mRNA has a deletion of 12 nucleotides, resulting...

Cataracts

Bilateral ocular cataracts are a consistent feature of WS and first appear or are reported in many patients by the second or third decades of life. The cataracts consist of posterior cortical and subcapsular opacification. Vacuoles and small punctate opacifications in other parts of the lens have also been noted, though are not a consistent part of the lens changes. This type of cataract, often referred to as juvenile, can be readily distinguished from the more common opacification of the lens...

Skeletal Muscle

The normal skeletal muscle consists of multinucleated cells called fibers. Each muscle fiber is an elongated cell surrounded by a plasma membrane called the sarco-lemma. Fibers contain myofilaments, contractile proteins that are responsible for muscle contractions. These fibers are grouped in fascicles and surrounded by connective tissue, the perimysium Bossen, 2000 . Skeletal muscles are connected to bone by tendons at each end. One of the most obvious effects of aging is a decline in muscle...

Human Studies Of Macular Degeneration

Mendelian linkage and association studies In addition to ARMD, several Mendelian forms of macular degenerations have been described. The age of onset, pattern of inheritance, and clinical characteristics of these diseases vary widely. To date, about 17 human Mendelian macular degeneration genes have been mapped Tuo, Bojanowski, and Chan, 2004 . So far genes for nine different forms of human Mendelian macular degenerations have been identified using a positional cloning approach. These genes can...

Role Of The Physical Environment As People

Environmental gerontology or, as it may be labeled, the ecology of aging, typically is identified with the description, explanation, and modification optimization of the relation between the elderly person and his or her physical environment Wahl, 2001 Wahl and Gitlin, In press . Furthermore, by drawing from German psychologist Kurt Lewin's 1936 basic insight that behavior has to be seen as a function of the person and his or her environment, American psychologist M. Powell Lawton 1982 has...

Seeking The Prime Mover In Animal Models

The human sequence of the A peptide is particularly prone to aggregation in vitro and is required for deposition in vivo. The murine sequence contains three amino acid substitutions, F4G, Y10F, H13R, all in the hydrophilic N-terminus of the peptide Figure 11.2 , resulting in greatly reduced fibril-forming activity, which may explain why rats and mice don't spontaneously develop plaques. Initial attempts at modeling amyloid deposition involved infusion of the human sequence peptide or plaque...

Care Of Captive Bat Populations

Several species of bats have been maintained in captivity, and there is ample information available regarding the proper care of captive bats. The following is a brief summary of some basic considerations for the captive care of bats. We refer readers to books listed in the Resources section of this chapter for more detailed information. Generally, a researcher interested in maintaining a captive colony must consider roosting and flight needs, climate and lighting needs, nutritional needs, and...

Evidence for Ovarian Senescence in Rhesus Monkeys

Female Lifespan Ovarian Reserve

The number of potentially viable oocytes available to the reproducing female depends on the size of the primordial follicle population within the ovary. In humans, primarily due to follicular atresia and secondarily because of follicular recruitment, the numbers of primordial follicles decrease dramatically from birth to the onset of menopause. At the end of the reproductive lifespan, the ''ovarian reserve'' of viable follicles and oocytes is essentially depleted, and the ovary is said to be...