C

Raising the adults on food which contained only 33 of the nutrients found in the standard food allowed a 34-day increase in the median life span and a 31-day increase in the maximum life span (Pletcher et al., 2002). Analysis of the age-specific mortality rates for this experiment showed that they did not begin to increase from the minimal values observed in the young until 15 days in the control animals and about 45 days in the CR animals. If this increase in the age-specific mortality...

Brain Imaging In The

Recent advances in brain imaging technology permit noninvasive analyses of metabolic, vascular, and structural changes associated with normal and pathological aging. In addition to improved image acquisition devices, computer technology and software development have also advanced, producing more sophisticated methods for analyzing brain imaging data. Techniques such as manual-based region of interest (ROI) planimetry and voxel-based morphometry (VBM), widely used in humans, indicate that...

Aneuploidy Causing Mechanisms

Mosaicism is defined as differences in chromosome numbers among blastomeres of the same embryo, that is, nondisjunction errors occurring during mitosis. We might expect to find substantial frequencies of mosaicism within macaque embryos, because this has been the experience with human embryos produced in vitro (Munne et al., 2002). For any single embryo, a chromosomal segregation error during second meiosis will result in all cells being aneuploid. However, an error Figure 39.3 Human (left) and...

Alzheimerlike Alterations

The brain of AD patients is characterized by the consistent presence of SP and NFT, two hallmarks of structural protein precipitation occurring in neuronal aging. SP and NFT are also found, but to a lesser degree, in the brain of elderly, cognitive intact individuals. SP are focal and irregular alterations of the neuropil ranging in size from 30 to 30,000 m2 or more according to the age of the subject, brain size, and neuronal size distribution in the brain cortex. SP appear as a lattice of...

References

Arking, R., Buck, S., Novoseltev, V.N., Hwangbo, D., and Lane, M. (2002). Genomic plasticity, energy allocations, and the extended longevity phenotypes of Drosophila. Ageing Res. Rev. 1, 209-228. Barja, G. (2002). Rate of generation of oxidative stress-related damage and animal longevity. Free Radical Biol. Med. 33, 1167-1172. Chapuisat, M., and Keller, L. (2002). Division of labour influences the rate of ageing in weaver ant workers. Prod. R. Soc. Lond. B. 269, 909-913. Charlesworth, B....

Conclusion

Applying principles of ethics to aging research is more than one project. It consists in part of artfully and ethically responding to the obvious, using accepted principles of ethics. We know, for example, that some persons are impaired, that impairment makes it difficult to get informed consent, and that we ought to take additional measures to protect those persons. We know some of the measures that can be effective in enhancing informed consent or in protecting those who cannot consent. Some...

Comparative Aspects

While we argue here that the honeybee is an emerging model organism in aging research, it has already attained the status of a model organism in several other biological disciplines and it serves as the model social insect. Social evolution has generated a wide variety of social systems with unique selection pressures and adaptations that provide many opportunities for testing ultimate theories of aging, as well as study the proximate causes of naturally evolved aging differentials. Sociality...

Psychiatric Diseases And Symptoms

Alzheimer's disease and other dementias Senile dementia of the Alzheimer's type (AD) is often associated with sleep impairment, and several kinds of disturbances have been described, such as reduction of sleep efficiency and of the total length of sleep. There is also a relationship between the severity of the sleep disturbance and the severity of the dementia. Patients with AD have an increased number and duration of awakenings, an increased percentage of stage 1 sleep, reduced slow-wave...

Genetic Epidemiology

Studies of muscle biology, including mechanisms of development, atrophy, and hypertrophy, from cell and animal models have provided information about a large number of genes that may have an additional role in sarcopenia during aging. One way to study the roles of such genes in sarcopenia is to use genetic epidemiology (Mehrian-Shai and Reichardt, 2004). Genetic epidemiology studies the association of naturally occurring alleles of genes with the extent or rate of sarcopenia in a clinical...

Fertility and Aging Men An Introduction to the Male Biological Clock

Lambert, Peter N. Schlegel, and Harry Fisch Data obtained in the past decade suggested a worldwide decline in male fertility. The increase in paternal age is both a personal problem for couples and a public health problem because of the simple fact that male fertility declines with age. Journal articles by Kidd and Ford demonstrate that men over the age of 35 are twice as likely to be infertile as men younger than 25. In addition, a study of couples undergoing fertility...

Migration Of Mitochondria In Oocytes And Embryos

Data from our laboratory using hamsters and rhesus monkeys show that during fertilization, active mitochondria become unequally distributed in the oocyte cytoplasm. In general, active mitochondria relocate to surround the pronuclei (Barnett et al., 1996, 1997 Squirrell et al., 2003). In hamster oocytes, active mitochondria were homogeneously distributed in the oocyte cytoplasm before activation by spermatozoa, but a few hours later they began to translocate to the peripronuclear region...

Internet Resources

Science of Aging Knowledge Environment (SAGE KE) (http sageke.sciencemag.org) Alzheimer Research Forum (http www.alzforum.org) Online Mendelian Inheritance in Man (OMIM) (http NIH's Genetics Home Reference (http ghr.nlm.nih.gov ) Alzforum's database of genes (http www.alzforum.org res com gen default.asp) Alzforum's database of mutations (http www.alzforum. org res com mut default.asp) University of Washington's Werner Syndrome site (http Diabetes Genome Anatomy Project (http www. SAGE KE's...

The Physiology Of Sleep And Its Aging

The sleep wake cycle and the 24-hour rhythm of the body temperature are regulated by a circadian periodicity that originates from the suprachiasmatic nucleus in the hypothalamus. In the morning we wake up, our body temperature increases from the nocturnal level, and we are able to be active throughout the day. In the late evening, when it is dark, we normally go to bed, and after a while we fall asleep. With reference to the EEG pattern, sleep is divided into five different stages Stage 1 Light...

Experimental Procedures And Manipulations

The transition between field and laboratory procedures is gradual in honeybee research, and often a combination of both is desirable. Honeybees prove unproblematic in both contexts, but a few points have to be kept in mind. As members of a social group, honeybees are greatly affected by their social environment, and individuals readily adjust their life history to environmental conditions (Schulz et al., 1998 Pankiw, 2003). For this reason, experimental handling and stress (including social...

Info

Two other RecQ helicase deficiency syndromes, (Monnat, 2001). Several pathologic and clinical aspects of neoplasia in patients indicate that WS is a classical cancer predisposition syndrome. WS patients develop neoplasms at a comparatively early age and often display unusual sites of presentation (e.g., osteosarcoma of the patella) or less common histopathologic subtypes (e.g., follicular, as opposed to the more common papillary, type of thyroid carcinoma) than do population controls. The...

Beyond Physical Frailty Frailty Models that Include Illness Social and Psychological Status

Because of the likelihood that aging-related changes in physiology, functionality, and disease states may contribute to frailty, some authors have developed models of frailty that include measures of these domains. For example, Rockwood et al. (1999) developed and validated a brief clinical instrument to classify frailty in hospitalized patients that included measures of function, cognition, walking, and bladder bowel function as determining factors. Using Canadian provincial sampling frames...

Mri

Well validated Sensitive to small changes Less expensive equipment Very Accurate Reproducible Sensitive to small changes Very Accurate No Radiation Exposure Reproducible Overestimates Muscle Mass Needs trained operator Radiation Exposure Needs trained operator Expensive Equipment Needs trained operator Radiation Exposure Expensive Equipment Needs trained operator Measurement of muscle metabolites Muscle produces creatinine and 3-methylhistidine, which are excreted in the urine, allowing...

Recommended Resources

Bereiter-Hahn, J., and Voth, M. (1994). Dynamics of mitochondria in living cells shape changes, dislocations, fusion and fission of mitochondria. Microsc. Res. Tech. 27, 198-219. Bertoni-Freddari, C., Fattoretti, P., Paoloni, R., Caselli, U., Galeazzi, L., and Meier-Ruge, W. (1996). Synaptic structural dynamics and aging. Gerontology 42, 170-180. Bertoni-Freddari, C., Fattoretti, P., Paoloni, R., Caselli, U., Giorgetti, B., and Solazzi, M. (2003). Inverse correlation between mitochondrial size...

Sampling in Aging Research

As an example, take a seemingly simple research question. Suppose a researcher aims to detect the contribution of aging and diet to body mass index (BMI). One approach might be to measure height and weight in a sample of subjects believed to be representative of the general population at different ages, and then to test the association between age and BMI and report the result, seeking to explain the proposed association using age differences in dietary data. These three measures (age, diet,...

Table 581

Pathophysiologic mechanisms and risk factors common for both cardiovascular disease and Low Bone Mineral Density Associated with vascular disease Associated with increased vascular dysfunction Inhibits osteogenic differentiation and Endothelial Dysfunction oxidative stress, ox-LDL, diminished NO availability, thrombogenicity, VSMC proliferation Associated with BMD ox-LDL Inhibits osteoblastic differentiation Endothelial dysfunction, diminished NO production, plaque formation, neointima, cell...

New World Monkeys

The New World monkeys share some similarities in reproductive aging with their Old World counterparts, such as decreased follicular numbers, reduced numbers of steroid receptors, and lower levels of estrogen and progesterone with higher LH levels in anovulatory females (Tardif et al., 1992). However, these animals do not undergo menstruation rather, they have an estrous cycle (Hendrickx et al., 1995). Additionally, these animals appear to have moderate levels of estrogen and progesterone in the...

Comparison of Rodent Aging and Human Aging

A hallmark of aging in both humans and rodents is thymic involution or decrease in thymic mass. Although this suggests that the ability of the thymus to produce new naive T-cells decreases in combination with decreased progenitor production in the bone marrow, it would be predicted that peripheral T-cell numbers should decline with age. However, the impact on peripheral T-cell number appears to be minimal. This may be due to clonal expansion of mature memory and naive T-cells in the periphery....

Upper Airway Colonization

Colonization of the upper respiratory tract by both Gram-negative (GNB Enterobacteriaceae, P. aeruginosa) and Gram-positive bacteria (S. aureus) is more prevalent in the elderly and is related more to the severity of systemic illness and level of care than to age per se (Johanson et al., 1969 Valenti et al., 1978). Factors leading to colonization of the lower and upper respiratory tract include antibiotic therapy, endotracheal intubation, smoking, malnutrition, surgery, and any serious medical...

Chronological Aging in Yeast

The chronological life span of a yeast cell is defined as the length of time that a cell can maintain viability in a nondividing state. Chronological aging in yeast has been studied using a variety of different methods involving culturing cells into stationary phase, a quiescent state in which cells are metabolically active but nonreplicative. Compared to replicative aging, relatively few genes have been studied with respect to their effect on chronological life span yet, some of the important...

Nonhuman Primates as Models for Reproductive Aging and Human Inferti ity

Brenner Nonhuman primates are invaluable models for a wide range of basic and applied studies related to human health. In vitro production (IVP) of preimplantation embryos makes them available in significant numbers for embryo manipulations and research aimed at a variety of biomedical applications. Rhesus monkeys (Macaca mulatta) are well established models for many biomedical research studies into diseases affecting humans. Their basic physiology and...

Telomeres in Aging Birds

Delany This chapter describes the use of avian species (the domestic chicken Gallus domesticus in particular) as model organisms for research in telomere biology and aging. Presented here are key concepts of avian telomere biology including characteristics of the model the karyotype, telomere arrays, telomere shortening as a measure of the senescence phenotype or organismal aging, and telomerase activity in avian systems, including chicken embryonic stem cells,...

Bats as Models for Aging Research Advantages and Disadvantages

Uncovering differences and similarities in patterns of aging among various organisms from a broad phylo-genetic spectrum is likely to yield insight into universal mechanisms of senescence. The inclusion of out-groups in aging research would allow investigators to assess whether these mechanisms or traits are unique to a given study species or shared by a broader taxonomic group (Austad, 1997). Bats may be an excellent out-group because they share life history traits with primates and other...

Dietary Restriction

Dietary restriction is the only environmental manipulation that can bring robust extension of lifespan in a variety of model organisms, and is one of the most important themes in aging studies. Despite a great deal of effort, the precise mechanisms by which it works are not clear. Exploration of its mechanism has also been attempted in Drosophila, and though the picture is incomplete, progress is being made. Using demographic analyses, it has been shown that dietary restriction extends lifespan...

Prevention

Considering what just has been described, prevention of the degenerative factors induced by aging points to the application of an anti-apoptotic action to the nervous cells and glia of the human retina. One possible drug to perform this is acetyl-carnitine (ALCAR). In recent years attention has been focused on the advantageous influence of carnitine as an anti-apoptotic agent, above all as a molecule able to block the mitochondrial pathway in programmed cell death. Moreover ALCAR seems to have...

Why Study Spatial Memory and the Aging Hippocampus

Because age-associated memory impairment occurs only in specific systems of learning, it is important to focus on a kind of memory that is impaired similarly in both humans and in animals. The learning and memory of places is particularly appropriate for investigations into the mechanisms of cognitive aging for four reasons. First, diminished spatial memory capacity is associated with aging in humans and in animals (for review, see Gallagher and Rapp, 1997). Second, spatial learning and memory...

T Levels And Aging

Multiple cross-sectional and a few longitudinal studies have shown that serum T levels in men decrease with age (Deslypere et al., l984 Harman et al., 200l Morley et al., 2000). Age-related changes in total T underestimate changes in T available to target tissues. Several cross-sectional studies have shown that an increase of sex hormone binding globulin (SHBG) with aging and a decrease in T and free T (fT) levels are independent of changes in body mass index (Deslypere et al., l984 Morley et...

Cloning With Cancer Cells

Cancer cells display characteristics of continued cell growth, lack of crisis or senescence in culture, altered growth properties (e.g., anchorage independence), and an arrest or reversion of cellular differentiation. These characteristics can arise through a combination of somatic oncogenic mutations and loss of genomic integrity, including gene duplication amplification and loss of heterozygosity. An obvious question made approachable by the SCNT method is whether the oocyte can reprogram the...

Physiological And Biochemical Approaches

In order to elucidate mechanisms of aging, downstream effects of experimental manipulations that extend lifespan need to be fully characterized. For example, identification of a gene for a mutation that extends lifespan does not by itself explain how the gene achieves this. Here, physiological, biochemical, and cell biological studies become essential. Biochemical and cell biological approaches in Drosophila are well developed and easy to utilize. A large number of protocols for procedures such...

Testing Dietary Interventions in Autoimmune Prone Mice to Delay Aging and Age Associated Diseases

Typically, calorie restriction (CR) refers to a 30 to 40 reduction in food intake. CR feeding is important in aging research because CR is the only known experimental regimen to increase life span in all experimental models tested including yeast, nematodes, flies, and rodents (Jolly, 2004). The models examined are not malnourished because the CR diets have enriched vitamin and mineral content to compensate for the decreased food intake. CR is also potent at delaying the onset of diseases like...

Adipose Tissue Dysfunction

There are only scarce data on the contribution of adipose tissue dysfunction to the etiology of diabetes mellitus type 2 in relation to aging. The role of the adipose tissue is well established in relation to the increased release of free fatty acids (FFA) interfering with insulin signaling in insulin-sensitive tissues (Lewis et al., 2002). The loss of peripheral fat tissue in hereditary or acquired lipodystrophic syndromes has been associated with intramyocellular and intrahepatic fat...

Pharmacokinetic And Pharmacodynamic Considerations

The use of antidepressants in older patients can be complicated by several factors. Older individuals use multiple medications (two or more prescription drugs) three times more frequently than younger persons, increasing the potential for interactions. Age-related alterations in physiology can result in variable plasma drug concentrations, which may increase the number of adverse events, and the elderly may be more sensitive to adverse events (McDonald et al., 2002). Aging is associated with a...

Respect For Persons

The Belmont Report draws on a fundamental belief about what persons are in order to state how they ought to be treated. Human beings are autonomous, i.e., they are capable of self-determination by comprehending information and making considered judgments based on their own preferences. In ordinary life, this leads to the ethical principle that human beings should be respected by being given maximum freedom to make their own choices. In research, this same principle recognizes research...

Patterns of Senescence

Do all tissues of the fly age together and at the same rate Our early work suggested that both normal- and long-lived animals undergo the same sort of senescent process, losing different traits in the same sequence and at the same stage (Arking and Wells, 1992). Since the animals do not lose all functions at the same time, it also implies that different tissues age at different rates. Is there any data to support this implication The fact that there is a defined spatio-temporal pattern of gene...

Dietary Restriction and Oxidative Stress in Annual Fish Mutants

Once the mutagenesis is achieved, dietary resistant mutants and oxidative stress resistant mutants could be selected which might suggest genes involved in such a mechanism. For example a paraquat resistance mutant could be selected and then tested for lifespan extension. Similarly, mutants could be fed with a high fat and high nutrient diet which, in contrast to dietary restriction, should shorten the lifespan and the mutants that live under these conditions could be selected. However, these...

Cq

*MLS maximum reliably documented life span. C denotes longevity record from captive representatives W denotes record from mark-recapture records from wild populations. References National Research Council, 1981 Murphy and King, 1990 Ku and Sohal, 1993 Nottebohm et al., 1994 Holmes, et al., 2001 Holmes and Austad 1995a Austad, 1997 Ottinger, 2001 D. Nelson, pers. comm. F. Nottebohm, pers. comm. In addition, several teams of field ornithologists have published reports of aging-related declines in...

Replicative Aging in Yeast

The replicative life span of a yeast cell is determined by the number of daughter cells produced. Like other eukaryotic species, yeast replicative mortality follows Gompertz-Makeham kinetics, consistent with the hypothesis that similar processes underlie aging in yeast and aging in higher eukaryotes (Kaeberlein et al., 2001). Several studies have demonstrated that replicative aging is under both genetic and environmental regulation, and the SAGE KE Aging Genes and Interventions Database...

Subtypes

Even though a consensus has not been achieved on a specific definition for frailty, a number of subtypes of frailty have been proposed (see Table 50.4). Darwin wrote, ''Those who make many species are the 'splitters,' and those who make few are the 'lumpers''' (Gallagher, 2002). At this stage in its uncertain evolution, I would confess membership in the ''lumpers'' club and have reservations about ''splitting'' frailty into a number of ''species'' before we reach consensus on the defining...

Introduction The Chicken as a Model Organism

The versatility and utility of the domestic chicken as a developmental model was recently celebrated in a special issue of the journal Developmental Dynamics (2004) 229, 413-712 . The chicken is one of the primary models for vertebrate developmental biology and a model organism for the study of virology, immunology, cancer and gene regulation (Tickle, 2004 Antin and Konieczka, 2005). With a 6.6X draft sequence of its genome completed, the chicken is poised to become even more valuable in...

Vulnerable Population

Long-term care includes not only nursing homes but other environments such as day health centers, day hospitals, assisted living facilities, and home health services. Long-term care services all deal with concentrations of older adults who have significant ongoing needs for health care and various forms of personal assistance, depend on professionals to meet those needs, and spend substantial time in environments controlled by those professionals. The nursing home will be the focus of this...

Telomerase And T Cells

It is generally accepted that the clock that keeps track of cell divisions and signals cell cycle arrest in human cells is the telomere, a region at the end of each chromosome that consists of multiple repeats of a specific DNA sequence (Campisi et al., 2001). Due to the end-replication problem in copying the full length of the lagging DNA strand, normal somatic cells undergo progressive telomere shortening with cell division. Once the telomere reaches a certain critical length, the DNA damage...

Pathology Models Natural vs Engineered

AD symptoms are dominated by the progressive loss of cognitive function, although other modalities are affected, particularly in the later stages of the disease. Dementia, however, can result from multiple etiologies such as tumors, drugs, toxic agents, multiple cerebral infarcts, Lewy body disease, prionoses, and tauopathies, to name a few. Each disease generally presents a clinical picture that is distinct from the others, although areas of overlap are a persistent challenge for clinical...

Agerelated Development

The sleep pattern changes in parallel with aging. The time spent in deep sleep (slow-wave sleep) is decreased, and in the very elderly it may be absent. The number of awakenings increases with aging and in many elderly falling asleep after such awakenings becomes increasingly difficult. Elderly persons are therefore more troubled by spending time in the waking state in bed than younger adults. This decline in sleep maintenance is to some extent an expression of the age-related disorganization...

Standards

The arbitrary fluorescence units must be converted to amounts of H2O2. There are different possibilities to do this. One of them is to use H2O2 standards. However, M H2O2 solutions are unstable, and they should be prepared just before use from stable mM H2O2 solutions. An alternative is to use a glucose-glucose oxidase system as standard. In the presence of excess glucose, this couple generates H2O2 at a rate that depends on the amount of glucose oxidase added. For this purpose the following is...

Prognostic Indicators and Outcome

Items associated with a higher risk of in-hospital or 30-day mortality for older patients hospitalized with pneumonia are NHAP vs. CAP, bedridden status, altered mental status, absence of fever (< 37 C), absence of cough or chills, tachypnea (RR > 30 min), systemic hypotension (SBP < 90 mmHg), respiratory failure, CRP > 100mg L, multilobar involvement, pleural effusion, radiological signs of cavitation, suspicion of aspiration, presence of swallowing disorders, hypo-albuminemia,...

Historical Considerations

In historical perspective, aging has long been regarded as a purely biological and degenerative process. For example, Metchnikoff (1903), frequently cited as the creator of the term gerontology, made the argument in his Macrophage Theory that aging can be seen predominantly as an infectious disease, and, as a consequence, he believed that possible means to counteract such an infection (e.g., yogurt) would be helpful to delay aging. Given the strong biological and medical orientation of early...

Clinical Studies

Magnetic resonance imaging (MRI) is frequently used to document in vivo neuropathology in humans, such as stroke, multiple sclerosis and Alzheimer's disease. However, this imaging technology has also been applied to human aging studies, in both cross-sectional and longitudinal designs. The utility of repeated imaging is that each individual serves as his or her own baseline, avoiding many of the pitfalls of cross-sectional studies (secular trends). In general, these studies have concentrated on...

Atherogenesis and Aging

The prevalence of coronary artery disease increases with age (2002), and age itself is an independent risk factor for atherogenesis (Kannel and Gordon, 1980), suggesting that the biological milieu in aging populations is conducive to atheromatous lesion formation. Increased susceptibility to cellular stress and accrual of damage to vascular tissues are likely factors in the atherogenic milieu attributable to aging, yet the precise molecular processes underlying the age-associated events...

From Primary Cultures to the Aging Organism Lessons from Human T Lymphocytes

One of the prominent clinical features of human aging is the dramatic increase in morbidity and mortality due to infections. Aging is also the most significant risk factor for developing cancer. Both phenomena are related to the age-associated decline in immune function, particularly within the T cell compartment, the part of the immune system that patrols the body for cells that appear foreign, which would indicate they are infected or cancerous. Development of long-term cell culture protocols...

Cytochemistry Of Cytochrome Oxidase Activity In The Aging Brain

On the basis of the age-related constancy of the mitochondrial volume density (Vv), reported by many investigations using conventional electron microscopic methods, ATP supply is supposed to be adequate to the physiological housekeeping processes of the neuron in resting conditions. Namely, because of the known dynamic condition of mitochondrial morphology, the ultrastructural features of a given population of organelles (i.e., size, number, and volume density) appear to be modulated according...

Senescent T Cells And Mortality

The ultimate effect of T cells on aging is with respect to mortality itself. Early work suggested a connection, based on correlative data, between T cell proliferative responses in cell culture and mortality over the subsequent few years (Wikby et al., 1998). More recently, telomere analysis of total lymphocytes in a group of 60 year olds was shown to be predictive of mortality many years later (Cawthon et al., 2003). In these studies, it was shown that the individuals who had telomeres in the...

Human Models of Longevity

Centenarians, though rare at a prevalence of approximately one per 10,000 in industrialized countries, are among the fastest growing segment of our population. Familial studies indicate that exceptional longevity runs strongly in families, but as of yet, few genetic variations have been found to account for this survival advantage. It is likely that the prevalence of centenarians is increasing because achieving exceptional old age is multifactorial. A number of factors important to such...

The Aging Human Lung Age Associated Changes in Structure and Function

The human lung reaches the zenith of its functional capacity in the late second to the third decade of life, but age-associated changes in lung structure and function gradually ensue once this zenith has been reached. Although there is considerable interindividual variation, age-associated decline in lung function of healthy, nonsmoking individuals becomes apparent in the fifth to sixth decade of life when physiologic testing is performed. This decline in lung function coincides with...

Life Span Characteristics and Factors Which Are Responsible for Modifying an Insects Life Span

Although the aging pattern of insects, like that of other organisms, is doubtless under genetic control, it is extremely flexible, depending on several biotic and abiotic factors. Life span includes the longevity of all developmental stages an individual passes through during its life cycle. Individuals of insect species (as well as those of other species) experience a number of critical points in time during their life cycles, which influence the life span from eggs over larvae up to pupae and...

Models of Hypertension in Aging

Reckelhoff, Radu Iliescu, Licy Yanes, and Lourdes A. Fortepiani All forms of hypertension studied to date are caused by a defect in the handling of sodium and water by the kidney. There is a shift to the right in the pressure-natriuresis relationship (higher blood pressure) in which a hypertensive individual must increase blood pressure in order to excrete a normal sodium load. There are sex differences in blood pressure control in humans and animals, with males having higher blood...

On The Intertwined Role Of The Social And Physical Environment As People Age An Integrative Perspective

Interlinkages between the social and physical environment It generally appears that the bodies of knowledge related to the social context and to the physical context of aging have grown widely apart and independent of each other (Wahl and Lang, 2004). And it is indeed tempting to accept and acknowledge the separateness of the social and physical surroundings and their different role in aging. On a surface level, we might view the social environment as one that is apparently alive and actively...

Aging of Human Skin

Aging is defined as the accumulation of molecular damages. Skin accumulates damages because of the mitochondrial production of superoxide in the course of phosphorylative oxidation, and because of the exposure to external damaging agents, such as solar radiation, gravitational traction, infections, electric fields, psychological stress, cigarette smoke, specific foods, anoxia and other agents. All the factors contributing to the acceleration of the rate of accumulation of damages share the...

Brief Overview

The lens is susceptible to damage with aging since its cells cannot be replaced in this encapsulated tissue and its proteins cannot turn over in the nonnucleated fiber cells. Not only does this result in a decrease in function of the normal aged lens, but it also sets the stage for development of senescent cataract in individuals with additional environmental insult or genetic proclivity. As the lens ages, vacuoles and multilamellar bodies appear between fiber cells, and occasionally the fiber...

Genes Predisposing To Exceptional Longevity

The discovery of genetic variations that explain even 5 to 10 of the variation in survival to extreme old age could yield important clues about the cellular and biochemical mechanisms that affect basic mechanisms of aging and susceptibility to age-associated diseases. Until recently, only one genetic variation had been reproducibly associated with exceptional longevity, but even this might vary with ethnicity and other, as yet unknown sources of stratification. Schachter and colleagues (1994)...

Cancer

Cancer is a major health problem in developing countries, in many of which it is the second most common cause of death behind cardiovascular disease for all ages combined, and it will become of increasing importance in developing countries in the future as well. All of the major malignancies primarily affect the elderly, and the incidence of most common cancer types as well as of all tumors combined sharply increases with age. The incidence of cancer at different sites shows extreme variations...

Familiality Of Exceptional Longevity

Perls, Wilmoth, and colleagues (2002) analyzed the pedigrees of 444 centenarian families in the United States that included 2,092 siblings of centenarians. Survival was compared to 1900 birth cohort survival data from the U.S. Social Security Administration. As shown in Figure 47.1, female siblings had death rates at all ages that were about one-half the national level male siblings had a similar advantage at most ages, though diminished somewhat during adolescence and young adulthood. The...

Vaginal Symptoms

During the menopause transition, women may experience vaginal symptoms including vaginal dryness, itching, and dyspareunia (painful intercourse). These vaginal changes result from changes in the serum estradiol levels that drop precipitously just before the last period. The end organ response to this drop in estradiol results in less estrogen effect on the mucus membranes that line the vaginal wall. During the reproductive years the vaginal wall is composed of a highly estrogenized superficial...

Introduction

One of the most prevalent questions that people ask is whether disease causes aging, or aging causes disease. Disease does not cause aging because even the healthiest people will ultimately die. However, diseases can dramatically shorten life span. Aging, on the other hand, can increase the prevalence or likelihood of developing disease because there has simply been more time in older animals for cellular and molecular changes to occur. Thus, understanding both the biological process of aging...

Food Consumption by Old People

This is used to estimate the adequacy of dietary intake by old people, to relate dietary habits to nutritional status and then to health parameters, and to detect change in dietary habit following intervention (e.g., a nutritional education program). The nutritional literature is replete with studies of this type undertaken to meet a wide range of needs, from simple description of trends over time (e.g., Volkert et al., 2004) to the need to detect specific subgroups of old people at most risk...

Aging And Heat Shock Proteins

A characteristic feature of aging is a progressive impairment in the ability to maintain homeostasis in the face of environmental challenges. Heat shock proteins (Hsps) consist of a family of proteins that modulate stresses to the body. Hsps are ubiquitous, highly conserved proteins that have been found in the cells of all organisms studied thus far, including plants, bacteria, yeast, flies, and vertebrates. They are part of a multigene family that has been divided into 6 subfamilies based on...

Neurobiology of the Aging Brain

Carlo Bertoni-Freddari, Patrizia Fattoretti, Tiziana Casoli, and Giuseppina Di Stefano Different anatomical, histological, cellular, and sub-cellular alterations occur in the human brain during aging. Because of this wide variety of changes, often masked by compensating reactions, the identification of clear-cut decays due to age may constitute a difficult task. In the elderly, brain volume and weight decrease because of an insignificant loss of neurons, dendritic atrophy, and glial cells...

The Use of Mature Zebrafish Danio rerio as a Model for Human Aging and Disease

Keller, and Gavin Gillespie Zebrafish (Danio rerio) have been extensively utilized for understanding mechanisms of development. These studies have led to a wealth of resources including genetic tools, informational databases, and husbandry methods. In spite of all these resources, zebrafish have been underutilized for exploring the pathophysiology of disease and the aging process. Zebrafish offer several advantages over mammalian models for these studies, including the...

Genomic Tools

Information regarding web-based tools for sequence and bioinformatics analysis of avian species, BAC and cDNA libraries, chicken gene chips and a number of other websites of interest to researchers are contained in Table 29.5. For further detail on cDNA arrays for chicken gene expression analysis, see Burnside et al. (2005). Tutorials oriented toward the biologist new to bioinfor-matics can be found in Antin and Konieczka (2005). Both Antin and Konieczka (2005) and Dequeant and Pourquie (2005)...

The Possibility of Continuously Measuring Energy Metabolism

The small body size of insects offers the opportunity of continuously monitoring the total energy metabolism of a whole population over their total life span. This results in a ''metabolic picture.'' One can then test the influence of different treatments (e.g., temperature, light program, drugs, mating, virginity) on the energy consumption. We performed such measurements with Phormia using an infrared CO2 monitoring system (URAS). Due to the restriction on carbohydrates as energy-providing...

Aging Markers Based On Behavior And Circadian Rhythms

We are also attempting to document age-related changes in behavior and circadian rhythms of adult zebrafish. These studies on zebrafish aging markers have been pursued in collaboration with Irina Zhdanova at the Boston University School of Medicine. It has been reported that zebrafish is a diurnal vertebrate with a clear circadian pattern of daytime activity and nighttime rest (Cahill, 1996 Cahill, 2002 Dekens et al., 2003 Delaunay et al., 2000 Hurd et al., 1998 Kazimi and Cahill, 1999)....

Baxbcl2 Proteins

A differential and unique expression of apoptosis-regulating Bcl-2 family proteins has been demonstrated in the rat brain during the course of development and aging. Bcl-2 is expressed highly during embryonic development but is downregulated after birth (as early as one week) (Min et al., 2003). During naturally occurring cell death (NOCD) in the rat cerebral cortex, neurons expressing Bcl-2 may determine whether a neuron dies or survives, as over-expression of Bcl-2 in transgenic mice protects...

The Chronological Aging Assay

In its most general form, the chronological aging assay requires maintaining cells in a nondividing state for a prolonged period of time, while intermittently challenging a subset of the cell population for the ability to reenter the cell cycle and successfully begin vegetative growth. Several variations of this assay have been described (Fabrizio and Longo, 2003 MacLean et al., 2001), and many others can be imagined. The most commonly utilized variation involves growing cells into stationary...

Agerelated Impairment

Individual differences in age-related decline of the medial temporal lobe system have been observed in both humans and rodents (Gallagher et al., 1993 Bizon and Gallagher, 2005 Wilson et al., 2002). Across species, some aged subjects maintain mnemonic abilities well into advanced ages, whereas others experience loss of cognitive capacities relative to younger individuals. The basis for these individual differences in age-related cognition is a compelling focus of neurobiological research....

Caloric Restriction

Beginning with the early work of McCay and Maynard (1935) who reported a life-prolonging effect of caloric restriction in rats, numerous attempts have been made to study the underlying causes of this obviously general mechanism. It could be shown that a reduction of caloric intake of 30 to 50 prolonged the life of rodents up to 60 . The same results were obtained in young animals and in older adults which received the reduced diet later in life. The results of the studies on rodents could be...

Changing Demography And Its Impact

The age distribution of infection is governed by the intrinsic transmissibility of the infection, by contact patterns between age groups, and by the age distribution of immunity from past infection. Thus, changes in age distribution of the population itself will impact upon the transmission dynamics of infection, perhaps in complex ways, and these in turn will impact upon the future age distribution of infection and disease and of susceptibility and immunity the ''echoes'' of such perturbations...

Historical Perspective

In the developed world, nutritional research has its roots in recognition of the role of environmental factors in the origins of disease and the need for measures to improve the health of the public. Early emphasis was placed on the role of governments in public health matters, largely by removing the threats of foul air, poor hygiene in food preparation, and inadequate sanitation. Only much later, for reasons of food safety, did government interest turn to food. By 1900, a consensus had...

Why Are Freeliving S Ratti So Very Short Lived

One remaining oddity of S. ratti is that the free-living adults are really very short-lived, even by the standards of short-lived free-living nematode species. There are several possible explanations for this. First, the free-living adult phase of the life cycle is facultative (Viney, 1996). Hence when it does not occur, this may weaken selection on lifespan in the same manner as high extrinsic mortality. Second, it might result from antagonistic pleiotropy between the effects of genes on...

Elderly Persons

Christopher Hook The number of elders living in the U.S. is rapidly growing. Elders are uniquely burdened with illnesses and account for most deaths. In order to reduce morbidity and mortality experienced by elders, research involving elderly human subjects is needed. Contemporary codes of ethics and regulations governing research involving human subjects derive from the ethical principles of respect for persons, beneficence and justice. Investigators conducting research...

Environmental Factors

The individual prerequisites for a good night's sleep include a number of factors, such as a comfortable bed, fresh air in the bedroom, and a room that is not too cold Good sleep Poor sleep Good sleep Poor sleep Figure 71.2 Affirmative answers ( ) to the statement ''I am often sleepy in the daytime'' in relation to sex, age, and nocturnal sleep. Age (years) < 70 (white bars) 70-79 (dotted bars) > 80 (grey bars) (Asplund, 1996). and not too hot. A sleep partner also seems to be favorable for...

Epidemiology in Aging Research

In this chapter, we outline the definition of epidemiology and its historical development as a scientific discipline. Various conceptual approaches to epidemiology in aging research are introduced and discussed. We present the major epidemiological study designs and epidemiological measures, with a particular emphasis on peculiarities of their application in aging research. We review major fields of application of epidemiology in aging research, and we give examples of past and current...

Animal Models and Insights into Mechanisms of Lung Senescence

Changes that are similar to those in the aging human lung have been observed in both rodents and dogs (Pinkerton et al., 2004). The mouse makes an attractive model for mechanisms of lung senescence because of its relatively short lifespan, which is approximately 30 months for the strains used most commonly for research. A special strain, the senescence-accelerated mouse (SAM), has been established and has a median lifespan as low as 12 months (Takeda et al., 1981). An increase in total alveolar...

Avian Immunosenescence In The Wild

The physiological declines associated with senescence, including declines in both innate and acquired immune defenses against parasites and pathogenic microorganisms, have been thoroughly documented in laboratory animals and humans (Wollscheid-Lengeling, 2004). But the fitness deficits associated with advancing age in the wild, where animals experience a full range of natural hazards, stresses and diseases, are far less well understood (Miller, 1996). Recently, reliable aging-related declines...

Drosophila Models of Aging

The fruit fly, Drosophila melanogaster, is one of the most studied organisms in a variety of biological research fields, including studies on aging. The Droso-phila model has approached aging from a range of angles and contributed significantly to our understanding of aging. It has been a valuable model organism in the field and is expected to remain so. This chapter aims to introduce Drosophila as a model organism for the study of aging. First, the basic biology of Drosophila is described...

Drosophila

Rearing conditions of Drosophila can be found in different handbooks and internet pages (see the link at the end of the References). It should therefore suffice to give only a short comment. Breeding temperature is recommended between 18 and 25 C. Relative humidity in the breeding chamber should not be lower than 60 . A recipe for standard medium used in our institute is given as follows Add together 2.4 l water, 19.2 g agar, 192 g corn powder, 24 g soy flour (low fat), 43.2 g yeast, 180 g...

Future Directions

The various criteria proposed for frailty should be examined and compared. Do they describe the same group of individuals The answer is, ''probably not.'' How do they compare in predicting the outcomes associated with aging Can their components be linked to a common pathogenesis The respective validity, reliability, sensitivity to change, and practicality of the available criteria should be examined and contrasted. I suspect we will move away from clinical characteristics to the use of...

Hepatitis B

Age-related processes play a very important role in the population dynamics of hepatitis B virus (HBV) (Medley et al., 2001). This infection has similarly been estimated to result in 1 million deaths each year, but mainly in adulthood as a result of liver cancer and cirrhosis as with measles, however, there is a safe and effective vaccine. In contrast to measles, infection with HBV can result in persistent infection over a period of decades, and additionally the probability of persistent...

Graying And Loss Of Hair

Early graying and loss of hair are, together with short stature, among the earliest and most consistent changes observed in WS patients. Hair graying and loss start late in the second decade of life, and first affect the scalp and eyebrows. The loss of hair pigmentation is progressive and may lead over the course of a decade or more to complete loss of pigmentation. The premature graying and loss of hair also extend to other areas of the body, although these changes usually start later and may...

Model Equations

The design of the flow diagram also specifies the structure of the system of differential equations that constitutes the compartmental model. There is a direct correspondence between the flow diagram compartments and the model's state variables (representing the proportion or numbers in the population in each stage), and between the flows in the diagram and how the rates of change in the equations are specified. (The model equations may also incorporate subsidiary population structure such as...

Oooo

Titration of essential cellular factors > DEATH Figure 17.5. The ERC model for one cause of replicative aging in yeast. As described in the text, one cause of yeast aging is the production of extrachromosomal rDNA circles (ERCs) (Sinclair and Guarente 1997). Each rDNA repeat in the head-to-tail tandem array contains an origin of DNA replication sequence. Intrachromosomal crossing over by homologous recombination can loop out one or more repeats as an extrachromosomal circle. These circles can...

Pancreatic Beta Cell Dysfunction

The role of impaired insulin secretion due to pancreatic beta cell dysfunction in age-related glucose intolerance and type 2 diabetes has been well known from animal studies. In humans this aspect of type 2 diabetes has remained controversial during a long period (Chang et al., 2003). This was probably due to the earlier failure of taking into account the degree of insulin resistance in the evaluation of beta cell function in vivo with techniques such as the OGTT. The relationship between...

Transgenesis and Overexpression of Genes in Annual Fish

Transgenic technology has been recently introduced in zebrafish, and many promoters have been expressed in a tissue-specific manner. Conditional misexpression of genes in certain tissue has been achieved by using GAL4-UAS system (Scheer and Camnos-Ortega, 1999). In this system two different kinds of transgenic strains, called activator and effector lines, are developed. In the activator line, the GAL4 (yeast transcriptional activator) gene is placed under the control of a tissue cell specific...

Conclusions

The above suggestion that Nothobranchius would be a useful model for studying longevity genes is novel, and it is the first time that the genetic approach utilizing the annual fish is suggested, although Walford first noted the utility of annual fish in aging research (Liu and Walford, 1969). Such a utility will depend upon establishing conditions for chemical mutagenesis, isolating markers for linkage analysis, and identifying long-lived Nothobranchius mutants. Since these are straightforward,...

Ants as Naturally Longlived Insect Models for Aging

This chapter explains in what respects ants can be useful models in understanding the mechanisms of aging. It includes an introduction highlighting how ants fulfill a need for long-lived model systems in aging research. Three ant model systems are then described including their relevant natural history characteristics, collection and laboratory maintenance. Practical considerations are given for molecular studies and techniques. Finally, an overview is given of the available genomic resources...

Human Studies On Agerelated Cataracts

Linkage studies In addition to epidemiological evidence implicating genetic factors in age-related cataracts, a number of inherited cataracts with post-infantile age of onset or progression of the opacity throughout life have been described. Mutations in beaded filament specific protein 2 (BFSP2) can cause juvenile cataracts, the Marner and Volkmann cataracts can be progressive, mutations in aquaporin 0 (MIP) and yC-crystallin can cause progressive cataracts, and the CAAR locus is linked to...

Global Stroke Model

It has been stated that the focal stroke models are of greater relevance to the human condition of stroke. However, global ischemia is of clear relevance to cardiac arrest and asphyxia in humans. In addition, it should be noted that the physiological, biochemical, and functional measurements made during recovery from a global model of reversible ischemia may be important in identifying the molecular and cellular mechanism and action of potential neuroprotective agents. Global models of cerebral...

Table 422

Caspase-9 and -3 activation and PARP cleavage in the different models of hypoxia-ischemia or stroke in adult and neonatal rodent brains. Caspase-9 and caspase-3 activities were determined by fluorogenic LEDH and DEVD substrate cleavage, respectively. The presence of the 89 kDa of the PARP, poly (ADP-ribose) polymerase, a caspase-3 substrate, was described to be an apoptotic feature.