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...

Antioxidants

Free radical production is enhanced in both the ischemic core and penumbral following stroke injury, and this is believed to cause much of the damage seen in the core as well as penumbra. There are many agents that either block free radical production or inhibit its activation that have been shown to be very effective in experimental models. Uric acid is a well-known natural antioxidant present in fluids and tissues. Administration of uric acid resulted in a highly significant reduction in...

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...

References

Andolz, P., Bielsa, M., and Vila J. (1999). Evolution of semen quality in North-eastern Spain A study in 22,759 infertile men over a 36 year period. Hum Reprod 14, 731-735. Antonarakis, S. (1991). Parental origin of the extra chromosome in trisomy 21 as indicated by analysis of DNA polymorphisms. Down Syndrome Collaborative Group. N Engl J Med 324, 872-876. Auger, J., Kunstmann, J., Czyglik, F., and Jouannet, P. (1995). Decline in semen quality among fertile men in Paris during the past 20...

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...

Difficulties Of Including Elderly Study Participants In Epidemiologic Studies

A primary prerequisite for any epidemiological study is informed consent of study participants. Among the elderly, this may often be a difficult matter given the higher prevalence of cognitive and functional impairment compared to younger populations. Often, extensive data collections needed in many epidemiological studies may also be too exhausting for potential study participants with reduced general health status. In case of major cognitive impairment or dependence on nursing care,...

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...

Introduction

Normally, our brains do a masterful job of filtering and sorting the information that flows through our ears such that we are able to function in our acoustic world, be it conversing with a particularly charming individual at a social gathering, or immersing ourselves in a joyful piece of music. Unfortunately, as we get older, our sound world becomes impoverished as a result of the normal changes in peripheral auditory structures, which represent a significant challenge for hearing science and...

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...

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...

From Yeast Methuselah Genes to Evolutionary Medicine

The recent identification of many genes that regulate the life span of yeast, worms, flies, and mice has greatly enhanced our understanding of the mechanisms of aging. Saccharomyces cerevisiae has emerged as the simplest of the major model systems to study aging, thanks in part to the development of a chronological aging paradigm that has allowed a more direct comparison with higher eukaryotes. Remarkably, similar pathways regulate the chronological life span of yeast and of the other major...

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...

Info

Figure 80.3 The human Werner syndrome protein WRN and a summary of mutations identified in the WRN gene of Werner syndrome patients. The central box indicates the WRN open reading frame with amino acid residue numbering indicated on top, and cDNA bp coordinates below, the left end of the open reading frame. The positions of five protein motifs are indicated by shaded boxes and labels exonuclease and RecQ helicase domains, RecQ consensus (RQC) domain, the helicase and RNaseD-C-terminal (HRDC)...

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...

Qualitative Aspect Of The Photoreceptor Mosaic

The photoreceptor mosaic of aged retinas, without pathologic changes, is similar to that of young retinas. However, the aged retinas show two typical cytological aspects. The first is the presence of refractive particles of around 1 mm in diameter located at the ellipsoid-mioid junction of the cones. These refractive particles appear like refractive bodies or granules of lipofuscin that are found in the internal segments that begin to be observed after 30 to 40 years. The second aspect is the...

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...

Superovulation Of Rhesus Monkeys And Flushing Embryos From The Reproductive Tract

The term superovulation is used liberally in human clinical IVF, but in that context it implies ovarian stimulation with gonadotropins to recruit large numbers of follicles, which are then aspirated prior to ovulation to recover oocytes. In animal studies, superovulation usually means allowing or inducing gonadotropin-stimulated follicles to ovulate into the oviduct, followed by collection from the reproductive tract of oocytes for IVF or of embryos for further study in vitro. The U.S. cattle...

Mammalian Examples Of Lifeextension

It is well-established that longevity increased in the lineage leading to humans, yet the evolution of longevity occurred in other mammalian lineages as well Figure 2.3 . Thus it is possible, and even likely, that life-extending strategies vary according to phylogeny. In other words, different mechanisms for long life may have evolved independently in different mammalian lineages. Identifying these mechanisms could potentially allow us to employ them in human medicine. The best example is...

Modeling mtDNA Mutations and Aging in Different Species

How do these computational models account for the radically different aging rates that occur in different species Our simulations show that the time required for the clonal expansions of mtDNA mutations by random drift is proportional to the number of mtDNA molecules per cell, N, and the mtDNA half-life, Thaf Chinnery and Samuels, 1999 . However, neither of these parameters is believed to vary significantly across mammalian species. The simulations indicate that there is no biologically...

Model For The Ageimpaired Medial Temporal System

Difference Rat Human Hippocampus

The Morris water maze is a hippocampus-dependent task that has been described in detail in numerous publications e.g., Morris, 1984 Gallagher et al., 1993 Bizon et al., 2001 . Rodents use visual cues around a circular pool in order to learn the location of a platform submerged 2 cm below the surface of the water's surface see Figure 32.2 . In our training procedure, rats receive three trials each day for eight consecutive days. All cognitive testing occurs during the light cycle. At each...

T714i T714a V715m 1716v

Figure 11.2 Familial AD Mutations in pAPP. The amino acid sequence of the region of the Amyloid Precursor Protein that contains the Ap peptide is shown with the different secretase sites a-, p-, y- marked. The sequence numbering for the Ap peptide is above the sequence while the pAPP sequence numbering is below the sequence. Positions and amino acid changes of the various familial mutations in pAPP are indicated. eventually forming neurofibrillary tangles, neuropil threads, and vacuolar...

Quantification Of Cerebral Infarction

The size of the brain infarct in focal cerebral ischemia increases in size during the period of reperfusion see Figure 79.3 . This has been shown in animal models of stroke and in human stroke patients. The infarct volume is normally analyzed after 24 hours in transient focal ischemia models and after six hours in permanent focal ischemia models. The brain is removed, and coronal sections are cut 2 mm-thick slices in rats or 1-2 mm thick slices in mice through the entire rostro-caudal extent of...

Principles of Animal Use for Gerontological Research

Animals, and in particular rats and mice, have long been a mainstay of experimental work in biological gerontology. This chapter presents ten key principles that should be considered in designing and interpreting reports that use laboratory rodents to learn about aging. In a nutshell, experimenters are implored 1 to use mice that are neither too old nor 2 too young 3 to use more than two age groups 4 to use rodents that are demonstrably specific pathogen-free 5 to consider the use of...

Nonpoultry Domestic Avian Models For Aging Studies

Avian models for learning and neuroregeneration Small songbirds, including canaries, zebra finches, and sparrows, as well as small parrots and pigeons, have been used for decades in neurobiology, particularly in studies of song learning and reproductive and courtship behavior. More recently, these laboratory bird models have also become the focus of research on the potential for regeneration of certain brain regions. Male canaries normally change their songs each new breeding season as they...

Sequential Sound Segregation

A second form of primitive grouping takes place along the time axis, and auditory streaming acts as a striking psychophysical demonstration of how sequential sound segregation works see Figure 64.2C . In a typical experiment, participants are presented with ABA ABA sequences in which A and B are sinusoidal tones of different frequencies and is a silent interval. The frequency separation between the A and B tones is manipulated to promote either the perception of a single gallop-like rhythm ABA...

Effects of Oxidative Stress and Genotoxic Stress on Zebrafish Aging and Senescence

Several lines of evidence suggest that genotoxic or oxidative stress promote the aging process Campisi, 2005 Finkel and Holbrook, 2000 Lombard et al., 2005 . It is well known that the aging process diminishes the capability to adapt to environmental stresses. We hypothesized that genotoxic and oxidative stress leads to mutations and general declines in reproductive ability, ultimately producing the spectrum of age-related characteristics in zebrafish. Support for this idea comes from the fact...

Innate And Adaptive Immunity

The fundamental purpose of the immune system is to distinguish between self and non-self. Foreign antigens Copyright 2006 by Academic Press All rights of reproduction in any form reserved. are eliminated in a variety of ways by both the so-called innate and adaptive components of the immune system. The innate immune system deals with foreign invaders through rapid, albeit fairly nonspecific, responses. Moreover, there is no recall or memory within the innate immune system. By contrast, the...

Rate Of Living Metabolism And Oxidative Damage

The first substantive biological theory of aging, the rate of living theory, was developed from studies on Drosophila. The early work of Loeb and Northorp 1917 demonstrated that temperature was negatively associated with lifespan in Drosophila. Raymond Pearl, a biostatis-tician who worked on population genetics, put forward this phenomenon as the ''rate of living theory.'' He found that the coefficient relating lifespan to ambient temperature in flies had a magnitude between two and three,...

Extension in the Dwarf

Dwarf mice are remarkably long-lived. Congenital deficiency of growth hormone GH , prolactin, and thyroid-stimulating hormone TSH due to mutations at the Pit1 or Prop1 loci, as well as GH resistance due to targeted disruption of the GH receptor gene lead to major increase in both average and maximal lifespan. Prolonged longevity of Snell dwarf Pit1dw , Ames dwarf Prop1df , and GHRKO mice is associated with a major extension of ''health span'' and multiple symptoms of delayed aging. Suspected...

Conserved Nutrient Sensing Pathways As A Mediator Of Cr In Yeast

The dissociation of Sir2 from CR in yeast has profound implications for the likelihood that downstream molecular events associated with CR are conserved across evolutionarily divergent organisms. It seems certain that ERCs are a mechanism of aging private to yeast, as there is no evidence that ERCs accumulate with age or cause senescence in the cells of multicellular eukaryotes. CR, on the other hand, slows aging in nearly every organism studied. If CR is not regulating yeast longevity by...

Social Responsiveness In Aging Dogs

Like humans, dogs are highly social creatures. Dogs interact with other dogs and humans and share common environments with both species. In humans, demented individuals undergo several abnormal changes in social behavior. In the early stages of Alzheimer's disease, patients become withdrawn in social settings. As the disease progresses to within 4-7 years of disease onset, social function declines. Disruptive behaviors including agitation, restlessness, and aggression become more common....

Prospective Basic Studies of Aging and Senescence in Zebrafish

The potential maximum lifespan of zebrafish is more than five years Gerhard et al., 2002 , though the differences among strains as well as betwen genders need to be clarified. Thus, while searching for late age-onset disease models and long-lived mutants is extremely important and worthwhile trying, it will be tough and tedious work because of current paucity of baseline information on zebrafish aging. On the other hand, we have been planning to isolate zebrafish mutants like progeroid...

Basic Failure Models

Reliability of the system or its component refers to its ability to operate properly according to a specified standard Crowder et al., 1991 . Reliability is described by the reliability function S x , which is the probability that a system or component will carry out its mission through time x Rigdon and Basu, 2000 . The reliability function also called the survival function evaluated at time x is just the probability P, that the failure time X, is beyond time x. Thus, the reliability function...

Telomeric Aging Markers

All vertebrate telomeres contain a characteristic 6-base repeated sequence, TTAGGG Meyne et al., 1989 . According to the telomere hypothesis, DNA replication in somatic cells leads to telomere shortening, which forms the basis of a cellular mitotic clock Sherr and DePinho, 2000 . Moreover, several premature aging syndromes lead to accelerated loss of telomeric DNA, which eventually results in accelerated replicative senescence of the cells Kipling et al., 2004 Metcalfe et al., 1996 Pandita,...

The Importance Of Dna Doublestrand Break Repair

Importance Span Control

Double-strand breaks DSBs in DNA are highly toxic lesions that can be created through a variety of mechanisms, including effects of reactive oxygen species. Double-strand breaks are repaired by either of two mechanistically distinct DNA repair pathways, homologous recombination HR or nonhomologous end-joining NHEJ van Gent et al., 2001 . A key factor of DSB repair by NHEJ is the DNA-end-binding Ku70 Ku80 heterodimer. Mice harboring a null mutation in the Ku80 gene have a significantly shorter...

Pitfalls Of Avian Aging Studies In The Wild

Good studies of basic aging patterns and processes in wild animals in nature depend on the ability to quantify and repeatedly measure reliable biomarkers of aging in substantial numbers of individuals. The statistical approaches currently used by avian demographers are in many cases robust and sophisticated, taking into account potential biases inherent in this type of data. As we have illustrated above, bird studies have other advantages as well. On the other hand, studies of the effects of...

Table 223

Extrinsic factors that affect lifespan in Drosophi a Heat shock, cold stress, hypergravity, low levels of radiation Prolongs the duration of development time and extends adult lifespan results in smaller adult size Prolongs the duration of development time and extends adult lifespan results in larger adult size Fewer viable eggs and offspring have shorter lifespan Shortens lifespan Virgins live longer than mated flies in both sexes, but the magnitude of increase in lifespan is greater in...

Targeted Knockdown Of Zebrafish Telomerase To Recapitulate Dyskeratosis Congenita

Dyskeratosis congenita DC is a severe, inherited, bone marrow failure syndrome, with associated cutaneous and noncutaneous abnormalities. DC patients also show signs of premature aging and have an increased occurrence of cancer. Accelerated telomeric erosion is a molecular hallmark of DC Mitchell et al., 1999 Ruggero et al., 2003 . DC can originate through i mutations in DKC1, which result in X-linked recessive DC ii mutations in the RNA component of telomerase TERC , which result in autosomal...