Longevity Health and Wellness Protocol

Longevity Blueprint

This product was authored and created by Ben Green. This guy is a nutritionist and a consultant in matters regarding nutrition and health. With time, he has evolved into a fitness coach, author and also a bio hacker. His work was inspired by the observance of his chronological age being younger than the biological age. The man realized that at the age of 30-yeasr, his body functioned like that of a 20-year old boy. This product has the powerful protocols that am sure will change your life for good. The author realized that even the most influential well-being article only focuses on the physical fitness and nothing else. This eBook is designed to provide you a complete well-being evolution which covers beauty, fitness, health and longevity. It is an 8 week protocol with all the details that teaches you about the important parameters that adds to your longevity. The program has all the details to help you find out your current fitness level and later discover powerful practices that will break out your metabolism. Continue reading...

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Comparative Life Expectancy

Although data are collected by race and ethnicity, the National Center for Health Statistics does not publish life-expectancy tables for Latinos or Latino subgroup populations. Data, nonetheless, suggest that life expectancy for ethnic-minority groups (71.3 years) is less than for all races (75.0 years). The life-expectancy rate for African Americans (69.4 years) is substantially less (a difference of 6.2 years) than for whites (75.6 years) and, perhaps even more disturbing, has been steadily declining since at least 1984 (69.7 years in 1984, 69.5 years in 1985, 69.4 years in 1986, 69.2 years in 1990) (National Center for Health Statistics, 1997).

Longevity and Aging in Budding Yeast

This chapter presents an overview of the current understanding of how yeast ages and the genes and pathways that play a role in determining yeast chronological and replicative life span. Several genes, as well as calorie restriction, have been found to regulate aging similarly in yeast and multicellular eukaryotes, and these potentially conserved determinants of longevity are emphasized. Descriptions of the chronological and replicative life span assay are provided in enough detail to allow a researcher with common knowledge of yeast methods to carry out his or her own aging studies.

Study of Tradeoffs Between Physical Activities Reproduction and Longevity

The comparative gerontologist often uses a theory which is assumed to explain the different longevities of organisms. This theory known as ''disposable soma theory'' was introduced into the studies of aging by Kirkwood (1977). The central thought is that the life history of a species in general is characterized by limited resources (constraints) of variable nature. That means that trade-offs exist between key life history variables and such trade-offs favor the allocation of energy between reproduction and maintenance of body constituents. Kirkwood argued that this universal theory should also be adaptable to humans. Together with Westendorp he had the opportunity to study the birth and death rates of about 35,000 males and females of the British aristocracy living between 740 and 1875. The main result was a negative correlation between longevity of females and the number of progeny (Westendorp and Kirkwood, 1998). Recent studies do not agree with these data (Lycett et al., 2000)....

The Three Longevity Phenotypes of Drosophila

One fact that has emerged from the past several decades of aging research is that aging is not simple. The work that my colleagues and I have done on Drosophila longevity bears this out. We reported that aging in our Ra strain of wild-type flies is rather complex, being characterized by at least three different extended longevity phenotypes, each of which was induced by specific stimuli and had different demographic mortality and survival profiles (Arking et al., 2002). As shown in Figure 25.1A, the first longevity phenotype (Type 1) is a delayed onset of senescence that leads to a significant increase in both mean and maximum life span of the experimental strain.

Stress Resistance And Extended Longevity

It has long been observed that mild or nonlethal stress often has the apparently paradoxical effect of benefiting the organism by increasing its longevity (Minois, 2000). Conversely, it has also been suggested that all long-lived strains and mutants exhibit some form of stress resistance (Parsons, 1995 Johnson et al., 1996). This relationship is thought to reflect the fact that their natural environment usually exerts substantial, albeit variable, stresses on organisms. Evolutionary considerations of Darwinian fitness will thus impose a premium on genotypes conferring metabolic efficiency and stress resistance (Parsons, 1997, 2003). The magnitude of the effects of stress resistance on longevity are summarized in Table 25.3. We will examine four complementary lines of evidence bearing on the relationship of stress resistance and extended longevity in Drosophila. The first involves the use of strains selected for extended longevity, followed by an analysis of the mechanisms responsible...

Chaperones Aging and Longevity

To the phenotype of aging, as an involvement in the definition of longevity can be assumed from high levels of chaperone expression as a common denominator in conditions or procedures leading to an increase in cellular and species longevity as well as in the process of cellular immortalization. The inherent immortality of the embryonic stem cells implies that replicative senescence as possibly aging are epigenetic phenomena, possibly influenced by the progressive age-related epigenetic changes in promoter methylation that have the potential to permanently silence gene expression (Krall, 2005).

Krzisnik Krk Longevity

Bartke, A., and Brown-Borg, H. (2004). Life extension in the dwarf mouse. Curr Top Developmental Biology 63, 189-225. Bartke, A., Peluso, M.R., Moretz, N., Wright, C., Bonkowski, M., Winters, T.A., et al. (2004). Effects of Soy-derived diets on plasma and liver lipids, glucose tolerance, and longevity in normal, long-lived and short-lived mice. Horm. Metab. Res. 36, 550-558. Berryman, D.E., List, E.O., Coschigano, K.T., Behar, K., Kim, J.K., and Kopchick, J.J. (2004). Comparing adiposity profiles in three mouse models with altered GH signaling. Growth Hormone & IGF Research 14, 309-318. Besson, A., Salemi, S., Gallati, S., Jenal, A., Horn, R., Mullis, P.S., and Mullis, P.E. (2003). Reduced longevity in untreated patients with isolated growth hormone deficiency. J. Clin. Endocrinol. Metab. 88, 3664-3667. Borg, K.E., Brown-Borg, H.M., and Bartke, A. (1995). Assessment of the primary adrenal cortical and pancreatic hormone basal levels in relation to plasma glucose and age in the...

Multifactorial Model for Exceptional Longevity

The fact that siblings maintain half the mortality risk of their birth cohort from age 20 to extreme age suggests a multifactorial model for achieving exceptional longevity. For example, socio-demographic advantages may play key roles at younger ages, whereas genetic advantages may distinguish the ability to go from old age to extreme old age. Undoubtedly exceptional longevity is much more complicated, with temporally overlapping roles for major genes, polygenic, environmental, and stochastic components. Such a scenario would be consistent with a threshold model, where predisposition for exceptional longevity can be measured on a quantitative scale. Figure 47.2 illustrates the standard threshold model proposed by Falconer (Falconer, 1965), where it is predicted that the proportion of affected relatives will be highest among the most severely affected individuals. In the case of exceptional longevity, perhaps severity may be measured by additional years beyond a certain age (threshold)...

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 high-throughput longevity phenotyping is the chronological life-span assay in budding yeast. Chronological life span'' refers to the length of time a yeast cell is capable of maintaining viability in a nondividing, quiescent state (see Chapter 18 Longevity and Aging in the Budding Yeast). Traditionally, chronological life span has been measured by culturing cells in 5-50 mL volumes and periodically plating onto rich media and counting colonies (Fabrizio and Longo, 2003). A semiautomated method for...

Vitalism Materialism and Spontaneous Generation

A driving philosophical debate also underlay cell genesis and the origins of germs the ongoing contest between materialism and vitalism. That microbes did not arise spontaneously from bad air or from putrefied matter was an issue of profound importance for medical practice and epidemiology. Attempts to prove or disprove it led to innovative experimental designs and important sterilization techniques in the nineteenth century that became the basis of modern microbiology and the germ theory of disease. The same issues about materialism and vitalism underlay the debates over cell generation in Germany. Schleiden and Schwann had placed their theory about cell formation from disorganized organic materials in direct opposition to the vitalism, idealism, and teleology of Naturphilosophie.33 The apparent gap between inorganic and organic form is not unbridgeable, declared Schwann an organized body is not produced by a fundamental power which is guided in its operation by a definite idea, but...

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 TT polymorphic variant was observed to be significantly increased within a healthy aged Irish population, while conversely the TC genotype was significantly decreased. Also correlations have been observed between a polymorphism in the Hsp70-A1 gene promoter and low self-rated health in aged Danish twins (Singh et al., 2004) as well as impaired longevity in women (Altomare et al., 2003). A relationship between the level of chaperone expression and the longevity of species can be assumed from the...

Ginseng And The Ageing Process

Neuronal energy requirements remain high throughout life, the most efficient source of brain energy being aerobic glycolysis during which adenosine triphosphate (ATP) is continuously synthesised. The ageing process alters cerebral metabolism with lowered glucose and oxygen consumption producing reduced ATP synthesis in persons demonstrating senile cerebral insufficiency (Sebban, 1982). Studying the effect of ginseng extract G115 on rabbit brain both in vitro and in vivo, Samira et al. (1985) concluded that there was a significant increase of glucose uptake with a corresponding decrease of lactate, pyruvate and lactate pyruvate ratio, indicating aerobic rather than the less economical anaerobic pathway. Thus G115 can be considered as a metabolic stimulant for brain tissue at doses equivalent to the recommended single human therapeutic dose, suggesting that altered neuronal metabolism rather than impaired cerebral blood flow is the problem in old age. Li et al. (1997), using...

Life Expectancy In Parkinsonism

All of the parkinsonism variants limit mobility, and the increased tendency for falls and dysphagia predisposes these patients to life-threatening complications (33,34). Life expectancy prior to the widespread use of levodopa was significantly reduced. In one hospital based parkinsonism series during the 1950s and 1960s, the mean survival after onset was 10.8 years (35). Excluding postencephalitic parkinsonism, the mean survival was 9.42 years, which is frequently cited as the yardstick for the prelevodopa era life expectancy (35). Mean survival in the contemporary parkinsonism cases cannot be compared with that study. There have been significant social and health care advances leading to longer life in the general population, and one would expect that parkinsonism patients would share these survival gains. Comparisons for survival should be made matching for year of birth, gender, and region country. Kurtzke et al. (36) noted that patients in the 1980s were, on an average, five years...

Experimental Models Linking Diabetes Mellitus to Aging and Longevity

In some species, caloric restriction (CR) is associated with reduction of aging and increased longevity. It was observed that a reduced body size was correlated to an increased life span in mice, dogs, Caenorhabditis elegans, or Drosophila melanogaster. One very recent study could not find a clear general effect of body size on life span (Hafen, 2004 McCulloch et al., 2003). The question has been asked why smaller individuals would live longer. One explanation that has been put forward, mainly in invertebrates, is the homologous insulin IGF signaling (IIS). In C. elegans it was suggested that the IIS can act to limit the body size. However, in some wild-type strains this correlation was much less clear. Moreover, several mutations in C. elegans led to extended longevity phenotype. Among these are the genes involved in the insulin IGF-signaling pathway, such as daf-2 and age-1, or clk mutants related to respiratory metabolism. Similar results were obtained in Drosophila. The study in...

Avian Longevity Is Consistent With Evolutionary Predictions

Why do birds live so long In the past, it was often argued that life spans and aging rates in warm-blooded vertebrates were constrained by the ''rate of living'' (Pearl, 1928 Rose, 1991). This argument was based on a robust, positive correlation between animals' body size and longevity, and an equally strong, inverse association between life spans and basal metabolic rates. This generalization is clearly refuted, however, when the long life spans of birds and bats are compared with those of nonflying relatives of similar size. These disproportionately long-lived animals are particularly interesting to comparative gerontologists, especially considering the higher metabolic rates and lifetime oxygen expenditures

Aging And Longevity Of Cells

Aging and longevity of differentiated cells in vitro That replicative senescence the model of aging in vitro probably is related to a chaperone deficit can be assumed from the increase in life span obtained by transfection with protein-chaperones, as well as from the attainment of cellular immortalization by heat shock procedures or transfection with RNA-chaperones (Krall, 2004). Aging and longevity of differentiated cells in vivo The great variability in the life span of differentiated cells in the organism shows a direct correlation to the The inducibility of Hsp70 by heat shock is reduced to approximately 50 in old rat hepatocytes, suggesting that a reduced ability to express hsp70 in response to stress may be a common phenomenon underlying the aging process. This age-related decline in the Hsp70 stress response was reversed by caloric restriction (Heydari et al., 1996). There is a functional link between age-related decrements in Hsp70 expression and patho-physiological responses...

The familiality of exceptional longevity

Studying Mormon pedigrees from the Utah Population Database, Kerber and colleagues investigated the impact of family history upon the longevity of 78 994 individuals who achieved at least the age of 65 years (Kerber et al., 2001). The relative risk of survival (1s) calculated for siblings of probands achieving the 97th percentile of ''excess longevity'' (for males this corresponded with an age of 95 years, and for women with an age of 97 years) was 2.30. Recurrence risks among more distant relatives in the Mormon pedigrees remained significantly greater than 1.0 for numerous classes of relatives leading to the conclusion that single-gene effects were at play in this survival advantage. The Mormon study findings closely agree with a study of the Icelandic population in which first degree relatives of those living to the 95th percentile of surviving age were also almost twice as likely to live to the 95th percentile of survival compared with controls (Gudmundsson et al., 2000). Both...

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) from the French Centenarian Study noted that the Apolipoprotein E fi4 allele becomes markedly less frequent with advancing age. One of its counterparts, the e2 allele, becomes more frequent with advancing age in Caucasians (Rebeck et al., 1994). Discovering genes that could impart the ability to live to old age while compressing the period of disability toward the end of life should yield important insight into how the aging process increases susceptibility to diseases associated with aging, and...

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 longevity are becoming more prevalent with modern public health measures and interventions. Such a multiple trait model would predict that the more extreme the phenotype, the more likely discernible environmental and genetic characteristics are to be discovered that are important to achieving very old age, much of it disability-free. Thus studies of families highly clustered for longevity or studies of supercentenarains, people age 110 and older, hold promise of facilitating such discoveries.

Life Expectancy

Arguably the ultimate phenotype of premature aging is reduced life expectancy. It is estimated that the onset of diabetes in human subjects reduces the life expectancy by an average of 10 years. The effect of diabetes on life expectancy depends on the age of onset. In general, the older the patient is at the time of diagnosis of diabetes, the lesser its effect is on life expectancy. Nevertheless it appears that diabetes continues to be a major detriment even when the disease onset is in the seventh decade (Songer, 1995). of glycemic control as measured by glycated hemoglobin (HbAlc) levels (Stratton et al., 2000 Mooradian and Chehade, 2000). It is noteworthy that HbAlc appears to be a predictor of mortality even in nondiabetic populations (Khaw, 2001). These latter observations highlight the importance of glycemia and glycation as a predicator of life expectancy. It is also possible that postprandial blood glucose excursions that contribute to the HbAlc measurements to a greater...

The Influence Of Body Size

A number of factors correlate with tmax, and while this work is about species selection, not the methodology of comparative biology, there is one factor that must be mentioned body size (Promislow, 1993). Clearly, bigger species, including mammals, live longer, on average, than shorter-lived species (Austad, 2005). Exceptions exist and, for example, gorillas (Gorilla gorilla) are typically bigger than humans and still do not live longer than us. Likewise, bats live longer than predicted from their body size. Nonetheless, when comparing parameters across species it is crucial to take body size into consideration. Otherwise we could make the mistake of correlating some physiological factor with body size, not with longevity or aging. For example, early studies indicated that DNA repair capacity was higher in longer-lived mammals, arguing that DNA repair was a factor in aging (Hart and Setlow, 1974). Yet it has been argued that the correlation between DNA repair and longevity is due to...

Neurologic Aspects of Alzheimers Disease

Quoted from Gulliver's Travels by Jonathan Swift, 1726, on learning that although the Struldbruggs (immortals) live forever, they were not a living treasury of knowledge and wisdom . . . and oracle of the nation but became progressively demented with age. As for much of human history, average life expectancy was 20 to 30 but by 1801 reached 35.9 years in England and Wales.

Issues In Diagnosis And Treatment

For unclear reasons, the risk of developing AD is higher in Black and Hispanic compared to White populations. Although the influence of the ApoE4 polymorphism on increased AD risk is apparent in Blacks, it appears to be less potent compared to Whites. Interestingly, although Black populations in Africa and the United States have similar ApoeE4 allele frequencies, the risk of AD is much higher in the age-matched U.S. Black population. This suggests that unknown environmental factors such as diet or resultant comorbidities may be important culprits. Until recently, vascular dementia was the leading cause of dementia in Japan, but this is shifting to AD, despite a low ApoE4 allele frequency, as life expectancy increases and stroke risk factors such as hypertension are better managed.

Great Crested Grebe Podiceps cristatus

Conservation status Although once nearly extinct in Europe, this species has made an impressive comeback thanks to the eutrophica-tion (yoo-troh-fih-KAY-shun), the aging process, of lakes the lakes contain more food for the grebes as they age. Populations are stable in all ranges.

Demography Mortality and Health Statistics

The last century has seen a dramatic longevity rise in the industrialized world. Some Web sites aim to document this phenomenon and to provide information that might lead researchers to the factors that have caused this life-span gain. The Human Mortality Database, a joint effort between researchers at the University of California, Berkeley and the Max Planck Institute for Demographic Research in Rostock, Germany, currently provides detailed mortality and population data for 23 countries. Visitors can download and analyze these statistics to compare mortality trends in different regions over time. The site also provides links to other resources that contain useful information, such as cause of death, that is not included in the Human Mortality Database. The National Center for Health Statistics at the United States Center for Disease Control and Prevention contains a Data Warehouse on Trends in Health and Aging on its aging activities page. Users can view, chart, and download data on...

Longitudinal and Cross Sectional Studies

Study of changes in cognitive abilities during adulthood might involve administering appropriate measures of these abilities to groups of individuals of different ages from 20 to 80. The cross-sectional approach, which was firs used by Adolphe Quetelet in 1838, is less expensive and more efficient than the longitudinal approach but has its own drawbacks. One drawback is that the different age groups must be matched initially on variables that might confound the relationship between age and the variable of interest (the criterion variable). For example, in a study of changes in cognitive abilities over the life span, the investigator should match various age groups on education before comparing them on measures of cognitive abilities. This matching process is not always easy to do, and even so, it may still not be clear whether differences among selected age groups on the criterion variable are a result of the developmental process, cohort (generational, cultural, etc.) differences, or...

Targeted Screens for Small Molecules that Slow Aging

In addition to Sirtuins, several other genes have been identified that play a role in determining aging rate in multiple eukaryotic models. For example, stress and nutrient responsive kinases, including TOR and Akt homologs increase life span in several different organisms when function is decreased (Fabrizio et al., 2001 Kaeberlein et al., 2005b Kapahi et al., 2004 Vellai et al., 2003), and are likely to represent viable small molecule targets. Indeed, inhibitors of TOR, such as rapamycin and rapamycin analogues, are currently in clinical trials as anticancer agents. In general, genes that function to promote aging (increase longevity when function is reduced) are likely to make better candidates for high-throughput small molecule screening, as it is much easier to identify protein inhibitors rather than activators.

Minority Aging And Health Problems Ethnic Comparisons

While people in the United States are living longer, life expectancy remains lower for ethnic minorities (C. Lopez & Aguilera, 1991 U.S. Department of Health and Human Services, 1990a). Life expectancy for the general U.S. population increased from 69.7 years in 1960 to 74.9 years in 1988 and is projected to increase to 77.0 years in 2000 (U.S. Bureau of the Census, 1990d, p. 72).

Natural Models Of Alzheimerlike Pathology

In summary, nonhuman primates and canines have been invaluable in illuminating the biochemistry, cytology and genetics of senile plaques, amyloid angiopathy and tau pathology in the aging brain, and they remain useful for testing emerging therapies for neuro-degenerative diseases (Studzinski et al., 2005 Walker et al., 2005). However, for a variety of reasons, a major component of which is their longevity, research with these species is limited in scope. The emergence of genetically engineered rodent models has greatly accelerated the investigation of AD-like pathogenesis in vivo.

Cardiovascular Disease

Post myocardial infarction A dose of 4 g day l-carnitine over 12 months improved quality of life and increased life expectancy in patients who had suffered a Ml, according to a controlled study (Davini et al 1992). This included an improvement in heart rate, systolic arterial pressure, a decrease in anginal attacks, and improve

Statistical Inference Methods

Analysis of Variance (ANOVA) is another parametric statistical method. One-way ANOVA is a popular tool for comparing the means from several samples. For example, Weindruch et al. (1986) collected data from mice on the relationship between caloric intake and life expectancy. They randomly assigned female mice to feeding regimen groups where scientists regulated the caloric intake as well as the composition and quality of the nutrition in the diets of the mice. In this situation, comparisons of mean life expectancy between feeding groups can be made by using ANOVA. Keep in mind, however, that ANOVA is a parametric method and the validity of the assumptions underlying this method must be verified prior to performing this analysis.

Ethnic Differences In Death And Dying

Industrialization and modernization have resulted in remarkable declines in death rates and substantial increases in life expectancy through improvements in food production, public health, and medical care. These improvements have primarily affected infants, who, in premodern times, were the most vulnerable to malnutrition and widespread disease (Goldscheider, 1971). Such progress in life expectancy is mainly the result of reductions in infant and childhood mortality.

The Universality of Yeast Aging Mechanisms and Future Outlook

Another major advantage of yeast is the rapid phenotypic testing of candidate longevity genes. For example, the ease of gene deletion in yeast means that one can find a gene whose expression is up-regulated in a microarray experiment under one growth condition, and then delete this gene to determine if this up-regulation is actually required for this growth condition. When this experiment was done with all budding yeast genes, it was found that only 7 of yeast genes that were up-regulated were actually required for optimal growth under the test condition (Giaever et al., 2002). This sobering result means that many of the genes identified by microarray approaches in organisms such as humans are probably not the most important genes affecting the aging process, and some sort of validation is required. Since such gene deletion studies and aging experiments are difficult and long in mammalian systems, budding and fission yeast will

What Do Chronologically Aged Cells Die From

A third mechanism by which quiescent yeast cells might senesce is due to damage generated by oxidative stress. The free radical theory of aging posits that one cause of aging is the accumulation of macromolecular damage due to oxidative free radicals (Harman, 1956). There are several lines of evidence suggesting that oxidative damage plays a causal role in the chronological aging process of yeast cells. For example, loss of respiratory capacity increases with time spent in stationary phase, suggesting that mitochondrial damage accumulates during chronological aging (Fabrizio and Longo, 2003). Also consistent with the idea that oxidative damage is correlated with chronological longevity, mutation of either mitochondrial superoxide dismutase (Sod2) or cytosolic superoxide dismutase (Sod1) results in a substantial decrease in stationary phase survival (Longo et al., 1996). Finally, overexpression of both Sod2 and Sod1 increases chronological life span by about 30 , suggesting that...

Chronological Aging And Response To Stress

It has been proposed that aging in nondividing yeast cells is largely under the control of the transcription factors Msn2 and Msn4 (Fabrizio et al., 2001). Msn2 and Msn4 bind to stress response elements (STRE) contained in the promoters of many genes coding for proteins involved in adaptation to starvation and stress, such as heat shock proteins, catalase, superoxide dismutase, and glycogen and trehalose biosynthetic enzymes (Smith et al., 1998). Msn2 and Msn4 are repressed by the nutrient responsive kinases TOR, PKA, and Sch9, which promote phosphory-lation and exclusion of Msn2 4 from the nucleus. Mutation of CYR1 or deletion of SCH9 fails to increase chronological life span in an msn2D msn4D double mutant, consistent with the idea the enhanced longevity seen in these mutants is due to activation of Msn2 4-dependent targets (Fabrizio et al., 2001). In many ways the function of Msn2 and Msn4 as transcriptional regulators of the yeast chronological aging program parallels the role of...

Embracing Diversity Understanding Strainspecific Differences

As with other model systems used for aging-related research, strain-specific effects due to genetic diversity can have a large impact on longevity and other age-associated phenotypes in yeast. The importance of strain diversity for studies of aging consists of two distinct components. The first component of strain diversity is the large genetic variation between different laboratory strains commonly used in scientific research. Laboratory strains can have dramatically different life spans, ranging from an average of less than 10 generations to nearly 30 generations, for replicative life span (Kaeberlein et al., 2005a). This type of diversity is analogous to that seen between different inbred strains of mice, which also can have substantially different longevity and aging The second type of diversity relevant to aging-related research is the genetic divergence between domesticated laboratory yeast and wild isolates of S. cerevisiae. This type of diversity and its impact on yeast aging...

Macroevolution and Paleontology

Simpson's works made him the father of the taxic approach to paleontology, a field that employs changes in taxon richness and longevity to understand major patterns in the history of life (see chapter 7). This approach occupies a major part of the efforts of paleontologists today (e.g., Flessa and Imbrie 1973 Raup 1976a, 1976b Sepkoski 1981, 1984, 1993 Valentine 1969 Van Valen 1973b, 1984). Simpson contrasted longevities within major taxonomic groups. The variations and general correlations of taxonomic longevity, speciation, and extinction rates have been used extensively to draw inferences about the tempo and mode of evolution (e.g., Sepkoski 1984 Stanley 1979), although many criticisms have been leveled concerning the potential of taxonomic bias generated by differences in morphological description, systematic practice, and so on, among taxonomic groups (e.g., Levinton and Simon 1980 Patterson and Smith 1987 Schopf, Raup, Gould, and Simberloff 1975 Van Valen 1973a). An article by...

Neurophysiological Factors

Many supporters of a neurological explanation of age-related declines in intelligence view it as the result of small changes in the brain produced by high blood pressure, alcoholism, and other pathological conditions (Rinn, 1988). It is certainly true that intellectual functioning is affected by health status and that people with higher intellectual abilities are healthier and live longer than those with lower abilities. Self-reports of physical and mental health confirm the results of medical diagnoses in this regard (Perlmutter &

Substantive Issues Demographic Determinants of Population Aging

Using the stable population model, the effect of a change in fertility on the age composition of a population is found to be straightforward. A permanent shift to a lower fertility level, with no change in mortality rates, leads to an aging of the population. This result is not surprising, because it seems obvious that under similar mortality conditions, a population with lower fertility will have proportionately fewer children, and hence an older population, than one with higher fertility. Comparing stable populations with different fertility levels and similar levels of life expectancy shows the magnitude of the effect of a fertility decline. For example, in a stable population with life expectancy of 80 years, 11.9 of the population will be over age 65 if the gross reproduction rate (GRR) is 1.5, but 25.9 if the GRR is 0.8. Other comparisons of stable population age composition under differing fertility and mortality conditions can be made from data in Table 5.1. The effect of...

Recommendations To Improve Policy Practice And Research

Resist the urge of pursuing, with no limits, medical goals that combine the following beneficiaries are primarily the elderly indefinite life extension is sought, costs are high, and the population-wide benefits are slight. Instead, we should seek to advance research and health care that focus on quality, not quantity, of life. In terms of the individual's responsibility, Callahan claims that a person who cares about his or her society should value more than just medical progress. Each element of progress can bring expenditure of resources. Thus medical progress and increased life expectancy have both good and bad elements.

Physiological Signatures And Patterns Of Lifespan

Stage (up to 280 days reviewed by Omholt and Amdam, 2004). Consequently, the transitions among those three distinct life history states are key determinants of the lifespan of any individual worker (reviewed by Amdam and Page, 2005). Within each temporal caste, however, longevity is further conditional on physiological factors (Maurizio, 1950) (see below). Metabolic Rate (MR) MR is one physiological factor that may underlie the temporal, caste-associated mortality rates of honeybee workers. Forager MR is significantly higher than the MR of hive bees (for a discussion see Suarez et al., 1996), and the MR of a foraging bee constitutes one of the highest known mass-specific aerobe MRs among animals (approximately 3-fold higher than hummingbird flight muscle). Such intense activity is a major source of mechanical senescence in insects and causes mortality to increase as a function of age (reviewed by Finch, 1990). In accordance with their longevity, diutinus bees periodically exhibit low...

The Ant Model Systems

Sociality causes an increase in longevity. Redrawing of Figure 2 from Keller and Genoud 1997 showing how extreme life spans evolved multiple times in association with the evolution of sociality. Figure 24.1. Sociality causes an increase in longevity. Redrawing of Figure 2 from Keller and Genoud 1997 showing how extreme life spans evolved multiple times in association with the evolution of sociality.

Systematics and Macroevolutionary Hypotheses

Although there have been some heartening changes since the first edition of this book, a few paleontologists have avoided the obvious need to define the meanings of taxonomic levels, genealogical reconstruction, and systematics (e.g., Gould 1989). Genealogical aspects of systematics have been largely ignored in studies of taxonomic longevity, diversity, and rates of taxon turnover (e.g., Sepkoski 1981 Van Valen 1973b Valentine 1969). This omission weakens the clarity of macroevolu-tionary hypotheses, which often involve explanations of change between sets of character states in different taxa. A now celebrated example is the so-called extinction of the dinosaurs, whose characters did not become extinct if you accept the idea that birds descended from one dinosaur group. Genealogical considerations therefore muddy up the waters of what extinction really means.

The Role Of The Spleen In Red Cell Membrane Disorders

The spleen plays a vital role in red cell health and longevity. Because 5 of cardiac output per minute is filtered through the spleen, this organ has ample opportunity to survey red blood cells for imperfections. Only those red cells that are deemed flawless are conducted through the rest of the red cell journey. The four functions of the spleen have been explained in Chapter 2, but when considering red cell membrane defects, it is the splenic filtration function that is the most relevant. As each red cell passes through the spleen, the cell is inspected for imperfections. Now imperfections may take many forms from inclusions to parasites to abnormal hemoglobin products or an abnormal membrane. Inclusions may be removed from the cell, leaving the membrane intact and allowing the red cells to pass through the rest of circulation unharmed. But if the red cell has abnormal hemoglobin (such as seen in thalassemia) or abnormal membrane components, then red cell elasticity and deformability...

How Do Different Pathways Yield a Common Type I Phenotype

Longevity-extending mechanisms known to be operative in flies, which we have discussed above. The schematic is somewhat speculative in detail, but its tying together of the several known methods of inducing stress resistance with the expression of extended longevity as described in the foregoing text is most likely correct in concept. The important point to note is that all the interventions listed are known to induce the Type 1 longevity phenotype (i.e., delayed onset of senescence) (see Figure 25.1A). The ISS pathway, certainly, and the JNK pathway, probably, are involved in producing this phenotype. The details of the CR pathway are still being worked out. Even given our incomplete knowledge, it seems as if all inducers of the Type 1 phenotype work by effecting some common regulatory nexus, probably the dFOXO3 transcription factor that is known to activate or repress various stress resistance genes. The interesting thing about the Type 1 phenotype is that delaying the onset of...

Annual Fish as Models for Aging

We believe that Nothobranchius rachovvi, a killifish, is a better vertebrate model for longevity genetics because their maximum lifespan is about ten months (Herrera and Jagadeeswaran, 2004). Nothobranchius rachovvi are tele-ostei like zebrafish and have already been used in aging studies. They have been shown to begin senescent changes at approximately four months of age. They are relatively easy to breed and are approximately 2 inches in size. The females lay approximately 20 eggs per day. Nothobranchius rachovvi can breed even at an old age until the very end of their lives. This occurs because the natural habitat of these fish dries out seasonally. In order to preserve their species, these annual fish developed schemes to lay eggs up to the time of death. In the laboratory, eggs are collected in peat moss and then stored in a dry container for four months. The eggs hatch when placed in water, and they grow at 28-30 C. The larvae mature by the age of 3-4 weeks when males develop...

Advantages of the Genealogical Approach

Genealogies and character transitions. A framework established from a genealogical algorithm permits a useful analysis of character variation in the context of macro-evolutionary hypotheses. Many macroevolutionary hypotheses attempt to provide mechanisms to explain differential taxon longevity. Claims that taxon longevity depends on biogeographic range (e.g., Boucot 1978 Jackson 1974 Levinton 1974) or that taxon longevity is the result of differential speciation rate or survival of species (e.g., Stanley 1975 Vrba 1983) may depend partially on the nature of character variation within the clades under consideration. In many cases, adaptations of individuals influence the susceptibility to extinction of species and larger taxa. Although speciation rate may ensure survival of a taxon, the possession of certain characters may permit an entire clade to outlast others or might permit descendants of a given clade to invade a new habitat. The testing of such ideas requires a mapping of...

Avian Models Of Extremely Slow To Negligible Reproductive Aging

Patterns of reproductive aging vary even more widely among birds than among mammals studied to date. As predicted by evolutionary aging and life-history theory, the slower aging of birds relative to mammals is generally reflected in slower reproductive aging in birds of both sexes (for reviews, see Holmes et al., 2003 Holmes and Ottinger, 2003 2004). Bird species that mature and reproduce extremely slowly, including seabirds (e.g., albatrosses, terns, and gulls) and large raptors (e.g., condors), tend also to be among the longest-lived, with some species holding longevity records of 50 years or more. Long-lived animals with exceptionally slow reproductive aging likely have physiological or molecular mechanisms for prolonging fertility, and basic reproductive aging processes may differ significantly between long- and short-lived species (Finch, 1990 Austad, 1993 Martin et al., 1996 Austad and Holmes, 1999 vom Saal et al., 1994). With the exception of primates, however, few long-lived...

Anatomy And Function

Although a large body of literature has focused on the medial temporal lobe and the well-described age-related deficits in explicit or declarative memory that are dependent on this system, it is notable that other brain systems are also affected at advanced ages and contribute to losses in cognitive function. Frontal cortical and or striatal circuitry is strongly affected in both normal aging and in pathological conditions associated with the aging process (i.e., Alzheimer's and Parkinson's disease). Subjects with prefrontal dysfunction are deficient in their ability to alter a behavioral response in the face of changing contingencies. This type of cognitive deficit may be caused by a disruption of striatal outflow resulting in frontal cortex dysfunction in circuitry connecting the prefrontal cortex, striatum and thalamus.

Substantive Concerns

Human fertility has attracted great attention over the past half-century.1 In fact, the largest, coordinated social science research efforts in history (the World Fertility Surveys and Demographic Health Surveys) have had fertility as their focus. Motivation for this attention emanates from the important and wide-ranging consequences of fertility and fertility change. Fertility levels are key components of population change and have been, historically, the component most difficult to predict (Bongaarts and Bulatao 2000). Also, fertility levels alter cohort sizes that, in turn, impact a full set of age-graded institutions such as schools, the labor force, marriage, and social security. Finally, human fertility is strongly linked to parenting or social replacement, the process of socializing group members. Except perhaps for increasing longevity, no 20th-century change has impacted individual lives more than have fertility changes. Consider, for instance, the cascading consequences of...

Theoretical Issues General Conceptual Approaches

As evidenced in Wise's work, there is a growing interest in cross-disciplinary collaboration with social scientists on the part of public health and medical researchers. Further, I believe a consensus is emerging in support of the view expressed by Frank, who points out (citing Carey 1997) that, in demography, there is a growing recognition that studies of biology of death, mortality, longevity, and life are all informed by biological processes that demographers cannot afford to ignore'' (2001 563).

Hormesis Inverted U or JShaped Curves

The form of this dose-response curve may be either of an inverted U or a J shape, depending on the endpoint measured. In cases of endpoints such as growth, longevity, fecundity, and cognitive function, the response would be seen as an inverted U shape. In the case of disease incidence, it would be seen as a J shape (Figure 12) (Calabrese, 2005).

Advantages And Disadvantages Of The Model

However, the longevity of this species also presents a challenge for researchers. There are few opportunities to study an individual over the entire lifespan. Most often, intervention studies are more similar to a human clinical trial looking only at specific variables for a preset length Overall, the many advantages of rhesus monkeys for aging studies are also their disadvantages. Yet, no other animal model comes as close to resembling human systems. Furthermore, because there is a generalized recognition of the value of each individual animal, the nonhuman primate aging research community has developed into a collaborative effort to better understand and further characterize the aging process.

Historical Trends The Infant Mortality Transition

Vital statistics registration remains inadequate in most areas of the world today, and even modern-day international comparisons are difficult due to variability in definitions, completeness of registration, and data quality (United Nations 2001 12-16). Nevertheless, it is possible to say with some confidence that ''for most of human history, life expectancy probably fluctuated between 20 and 30 years'' (Weeks 1999 131). Life expectancies in this range imply that only 63 to 74 of infants survive the first year of life (Weeks 1999 Table 4.2). During the premodern period, IMRs were probably on the order of 260 to 370 per 1,000 live births. Some time during the latter part of the 19th century, there was a major reduction in infant mortality in Western Europe. Scholars seem to agree that the transition to lower infant mortality, as well as to lower child and adult mortality and longer life expectancy during this early period, was largely due to a major reduction in deaths from infectious...

Calorie Restriction An Effective Intervention in the Rhesus Model

Calorie restriction (CR) has been long recognized for its benefits to health and aging in a variety of species (Weindruch and Walford, 1988). These benefits have been demonstrated in numerous studies of invertebrate and vertebrate models, which have shown that CR is a robust method for slowing aging as evidenced by reduced incidence and delayed onset of age-related diseases, extension of mean and maximum lifespan, increased stress resistance, and improved function (Bordone and Guarente, 2005). However, longitudinal CR studies are difficult in nonhuman primates due to their long lifespan and availability of sufficient numbers of animals to conduct this type of a study (Roth et al., 2004). Long-term studies have focused on obesity and diabetes (University of Maryland Medical School), and on the impact of a nutritious, low calorie diet (30 CR) on aging processes, survival, and longevity (Wisconsin National Primate Research Center and NIA). The NIA and WNPRC studies represent the first...

Cost Effectiveness And Qualityoflife Issues

HAI chemotherapy is often perceived as a complex and costly form of treatment. An important question is therefore whether the clinical benefits of HAI therapy worth the tradeoffs in its risks and whether it is cost-effective. The Meta-analysis Group in Cancer undertook an economic analysis on the additional cost of HAI therapy over that of conventional treatment using data from the meta-analysis performed by the group in 1996 (57). Health-care costs were computed for the entire duration of follow-up, and were based on actual costs (in 1995 U.S. dollars) at two trial centers, in Paris, France and Palo Alto, California, U.S.A. (57). The average cost per patient for HAI (which included the pump and its placement, initial hospitalization, administration of chemotherapy, and all related complications) was US 29,562 in Paris and US 25,208 in Palo Alto. The additional cost over control treatment (systemic chemotherapy in five trials, chemotherapy or best supportive care in two trials) was US...

Quality Of Human Oocytes And Impact On Fertility

The quality or health of human oocytes is progressively diminished with age due to (i) inherent or genetic factors as part of the natural aging process and (ii) epigenetic factors such as nutrition, smoking and environmental effects. While reduced fertility in women derives in large part from diminished oocyte quality or health, there is currently no reliable way to measure this attribute, nor any real understanding of why it happens.

Cytoplasmic Evolution

Experimental embryologists as a group did not develop a coherent theory for evolutionary change. Some adopted pluralist models that combined both mechanistic and metaphysical conceptions. When Boveri, for example, asked what caused large changes in organization, he turned to psychic explanations. Similarly, Spemann's holistic outlook led him to combine both Lamarckism and psychic forces.37 He drew ideas from vitalists and from the idealist morphology of Goethe and the Naturphilosophen, still widely read in Germany.38

Models Of Health Care

The biomedical approach has been symbolized by the Greek hero Asclepius, the god of healing and medicine. It represents the approach to curing disease or correcting accidental imperfections or birth defects (Garman, 1996). This biomedical view of health gained favor for three centuries beginning in the 17 th century. The second view has been symbolized by Hygieia, the daughter of Ascle-pius, and represents the approach to discovery of healthy living for the purpose of achieving longevity and quality of life. This social view of health has regained favor since the mid-1970s with its emphasis on prevention rather than cure (Gar-man, 1996). Differences between the biomedical and social views of health are summarized in Table 1.1.

Data And Methods Conventional Methods and Techniques

Life expectancy and life span are also critical measures used in mortality analyses. Life span refers to the maximum number of years a person can live (Nam 1994). Life span for humans is currently 122 years, based on the life of Jeanne Louise Calment, of Arles, France, who died in 1997 (National Research Council 1997). This life span could increase if a single individual outlived Madame Calment. Life expectancy is a summary measure of the average number of additional years a group of individuals can expect to live at a given exact age (Rogers, Hummer, and Krueger 2003b). U.S. life expectancy has increased remarkably over the last century, from just 47 years in 1900 to the present 77 years (Anderson and DeTurk 2002 Minifio et al. 2002). Although the U.S. is now enjoying the highest life expectancy at birth ever achieved by individuals in this country, at least 20 other countries have higher overall life expectancies at birth. For instance, compared to a current U.S. life expectancy at...

MtDNA Damage and the Mitochondrial Theory of Aging

Several lines of evidence indirectly implicate mtDNA in longevity. The Framingham Longevity Study of Coronary Heart Disease has indicated that longevity is more strongly associated with age of maternal death than that of paternal death, suggesting that mtDNA inheritance might be involved. On the other hand, longevity was shown to be associated with certain mtDNA polymorphisms. For instance, Italian male centenarians have an increased incidence of mtDNA haplogroup J, whereas French and Japanese centenarians have increased incidences of G to A transition at mt9055 and C to A transversion at mt5178, respectively. However, a study of an Irish population failed to link longevity to any particular mitochondrial haplotype, suggesting that factors other than mtDNA polymorphism also may play a role in aging (Ross et al., 2001).

An Experimentally Induced Decrease In Oxidative Stress Retards Ageassociated Deterioration At The Organelle And

Simultaneous overexpression of Cu, Zn SOD, and CAT in Drosophila was shown to increase the maximum and average lifespan by one-third, to retard the age-related accumulation of oxidative damage to DNA and protein, to increase resistance to the oxidative effects of X-ray exposure, to attenuate the age-related increase in the rate of mitochondrial H2O2 generation, to increase the speed of walking, and to increase the metabolic potential defined as the total amount of oxygen consumed during the adult life per unit body weight (Orr and Sohal, 1994). Moreover, others have been able to extend the Drosophila lifespan by overexpressing either Mn-SOD or Cu,Zn-SOD in motor neurons. Very recently, it became possible to modestly increase longevity in mice by overexpressing mitochondrially targeted catalase (Schriner et al., 2005). However, Schriner's report is somewhat vulnerable to technical criticisms on the grounds of the experimentally observed mosaic expression of the transgene and...

MtDNA Repair and Aging

Mitochondrial DNA accumulates high levels of the mutagenic 8-oxodG, arguably the most important base damage caused by ROS, and it is widely believed to play a major role in the aging process (Hamilton et al., 2001). The important role played by DNA repair enzymes in the accumulation of this lesion is underscored by the fact that the liver mtDNA from knockout mice for 8-oxoguanine DNA glycosylase (OGG1, the glycosylase that recognizes this lesion) accumulates 20 times as much 8-oxodG as the mtDNA from WT control mice (de Souza-Pinto et al., 2001). Interestingly, several studies have indicated that OGG1 activity in mitochondrial extracts from old rats is higher compared to extracts from young animals, which is apparently at odds with the observed accumulation of 8-oxodG in mtDNA from older animals (Hudson et al., 1998 de Souza-Pinto et al., 2001). The theory that explains this apparent discrepancy was put forward by Szczesny et al., who have shown that in both hepatocytes from old mice...

Source Preparation and Antigen Loading Strategy

Several systems have been employed to load DCs with TAA. Loading MHC class I molecules with peptides derived from defined antigens is most commonly used, and is also applied to recently identified MHC class II helper epitopes. Although important for proof of concept studies, the use of peptides is limited because of their restriction to a given HLA type, the limited number of defined TAA, and the induction of a restricted repertoire of T-cell clones. Furthermore, quantity and longevity of peptide loading is difficult to control. Alternative strategies that provide both MHC class I and class II epitopes and lead to a diverse immune response involving many clones of CD4+ T cells and CTLs are needed. These include recombinant proteins, exosomes (vesicles rich in MHC-peptide complexes and heat shock proteins) (77), viral vectors, plasmid DNA, RNA transfection (78), dying tumor cells, opsonized tumors (38), immune complexes, or fusion of tumor cells and DCs (79). Few comparative data...

The management of high grade dysplasia

HGD poses a special dilemma for both the physician and patient. The factors to be weighed are multiple and not always quantifiable. These include the variable natural history of HGD, interobserver variability in reading HGD, the difficulty of ruling out synchronous EAC, the patient as a surgical candidate, the risk aversion of the patient, and the expertise of the available institution (Table 3). These factors have to be addressed for and with the individual patient to determine an appropriate management strategy. HGD associated with a mass or mucosal irregularity is more likely to have early EAC and even regional nodal involvement 48 , 49 . The most recent experience with patients having only HGD prior to esophagectomy demonstrates a lower likelihood of unexpected cancer in the resected specimen - 17 from 1994-2001 versus 43 from 1982-1994 50 . Once there is cancer below the muscularis mucosa as documented by EMR or endoscopic ultrasound, endoscopic therapy is no longer appropriate...

Hormonereplacement Therapy

Years) hormone-replacement therapy (HRT). Beral et al.57 found an excess incidence of six breast cancers in 1000 women who had used HRT for more than 10 years. In addition, the risks were greater when a combined estrogen and progesterone preparation was used compared with estrogen alone.58,59 For the majority of women, the benefits in terms of protection against osteoporosis outweigh the breast cancer risk. However, one model has shown that, for women who have a 30 lifetime breast cancer risk and an average risk of cardiac events, life expectancy is no longer increased. In this group, HRT should be used with caution or for short

Agerelated Changes in Hormones and Their Receptors in Animal Models of Female Reproductive Senescence

Traditionally, the onset and progression of menopause in humans has been attributed to ovarian follicular decline. Because the follicles are the primary source of circulating estrogens, these age-related changes lead to a number of symptoms such as hot flashes, mood swings, irritability, and depression, as well as increased risk of osteoporosis, cardiovascular disease, and age-associated diseases. Recent research indicates that along with the ovarian changes at menopause, the hypothalamic and pituitary levels of the reproductive axis also undergo significant changes during reproductive aging. Indeed, current research suggests a neural, as well as hormonal, mechanism involved in the menopausal process. A number of animal models are available to study these processes, most commonly the nonhuman primates and rodents, and to a lesser extent, avian systems. Here, we will discuss Old and New World monkey models, rats, mice (wild type, transgenic, and genetically modified), and birds as...

Why Is Screening Less Expensive And More Beneficial In Older Women

Since cancer is less common in the younger group, a slight benefit of screening women under age 50 would mean that the cost of saving one life by mammographic screening in this age group could be substantial. Salzmann et al.10 estimated that biennial screening of women aged 50 to 69 would increase life expectancy by 12 days, and cost 704 per woman or 21,400 per year of life saved. Extending screening to every 18 months for women aged 40 to 49 would only increase life expectancy by 2.5 days, and would increase the costs by 676 per woman or 105,000 per year of life saved.

Zebrafish as a Model for Aging

Many species of fish have been used as an experimental model for aging (Woodhead 1978 Patnaik et al., 1994 Woodhead 1998) thus in addition to defining mechanisms of disease, zebrafish may be useful for exploring the process of aging. Recent studies have provided initial evidence that zebrafish have a median lifespan of approximately 36 to 42 months with a maximum lifespan of up to 66 months (Gerhard et al., 2002b), indicating that zebrafish undergo an age-related increase in mortality rate. More recently, a shorter median and maximum lifespan was reported for zebrafish, with 31 and 45 months, respectively (Herrera et al., 2004). The different results in these two studies may be a reflection of strain variation and differences in housing and environmental parameters. These findings, however, set the groundwork for identification of genes that control longevity. Aging zebrafish have been demonstrated to develop several phenotypes similar to aging mammals (Table 27.1), including the...

Disorders of female reproductive life

It should be noted at some point that there are general effects of gender on health. Females consult more frequently for all health problems, including neurotic conditions, throughout life. Prevalence of neurotic conditions is higher in females than males. Males have an excess of conduct disorder as children, and of criminality and substance misuse as adults. Males with psychotic disorders such as schizophrenia do worse than females. Females live longer. It has been suggested that men may need special services (Kennedy, 2001).

Heritability Estimates

Twin studies have estimated the heritability of life expectancy to range between 25 and 30 (McGue, Vaupel, Holm, and Harvald, 1993). These twin studies cannot infer the heritability of living to extreme old age because the oldest subjects in these studies are only octogenarians. In contrast, centenarians who live an additional 15 to 20 years beyond average life expectancy may require more than an advantage in their habits and environment. They may require a genetic advantage that translates into a significant inherited component to exceptional longevity. Some estimates are higher when the phenotype is more specific, as in the case of cognitive function at very old age (McClearn, 1997). Centenarians and their family members may have or lack certain genetic characteristics that result in a significant survival advantage.

Recommended Resources

Barzilai, N., Atzmon, G., Schechter, C., Schaefer, E.J., Cupples, A.L., Lipton, R. et al. (2003). Unique lipopro-tein phenotype and genotype in humans with exceptional longevity. JAMA 290, 2030-2040. An important phenotypic discovery that led to a genetic association with exceptional longevity and a demonstration of the power of studying centenarian families for discovering phenotypes and genotypes that play important roles in survival to exceptional old age. Hazzard, W.R. (2001). What heterogeneity among centenarians can teach us about genetics, aging, and longevity. J Am Geriatr Soc 49, 1568-1569. An important perspective of how complicated and subtle studies of aging and longevity can be. Herskind, A.M., McGue, M., Holm, N.V., Sorensen, T.I., Harvald, B., and Vaupel, J.W. (1996). The herita-bility of human longevity a population-based study of 2872 Danish twin pairs born 1870-1900. Hum Genet 97, 319-323. Kenneth W. Wachter and Caleb E. Finch, Eds. Between Zeus and the Salmon, The...

Acquired mtDNA Mutations Clonal Expansion and Their Relationship with Aging

Dysfunctional mitochondria and mutated mtDNA are associated with the aging process in a wide range of species, from C. elegans to humans. A recent experiment showed that mice with a mutated mitochondrial poly-merase had an increased rate of mtDNA mutation and suffered from accelerated aging (Trifunovic et al., 2004). This was the first experiment to deliberately manipulate the rate of mutation of mtDNA in an organism and to show a direct effect on the rate of aging.

Acquired mtDna Mutations

We have used two slightly different computational models to represent the somatic mutations that occur in mtDNA as part of the aging process. One method is to tie mutation to the replication process, to represent mutations that arise from replication errors. In this case, at every mtDNA replication event there is some probability Pmut that a new mtDNA mutation will be created. An alternative method is to model mutation formation independent of the mtDNA replication process. Then, over every time interval At there is a probability Pmut that a mtDNA molecule may be converted to a new mutation. Unless the replication rate is varying with time in the model, there is little significant difference between these two models for de novo mtDNA mutation formation. The parameter Pmut can also be made a function of time to represent changing mutation conditions, such as periods of increased radiation exposure, for example.

Memory Metaphors of Memory

However, while the spatial metaphor has shown extraordinary longevity, there have been some interesting changes over time in the precise form of analogy used. In particular, technological advances have influenced theoretical conceptualisations The original Greek analogies were based on wax tablets and aviaries these were superseded by analogies involving switchboards, gramophones, tape recorders, libraries, conveyor belts, and underground maps. Most recently, the workings of human memory have been compared to computer functioning and it has been suggested that the various memory stores found in computers have their counterparts in the human memory system. (Eysenck, 1984, pp. 79-80)

The Evolutionist Phylogeneticist Conflict and Classification

Apparent progressive sequences create the most problems because evolutionary sys-tematists wish to recognize grades of evolution by equal ranks, whereas the Hennigian system seems to require that more advanced groups be of lower rank. For example, evolutionary systematists would accept the equal ranking of pelycosaurs, therapsids, and mammals, because it is believed that the mammals, even though derived within the therapsids, are an important new grade of organization, which permitted an extensive evolutionary radiation. Again, as long as the cladal structure is preserved explicitly, one does not necessarily sacrifice any information. This issue lies at the heart of the analysis of fossil data, particularly that of taxonomic survivorship and longevity studies (e.g., Levinton 1974 Raup 1978 Van Valen 1973b). Such analyses would lose important information, if the classification obeyed Hennigian principles, because an analysis of taxonomic longevity will have ecological meaning only if...

North American porcupine

Mating typically occurs only once a year in the fall, during a period of eight to 12 hours when the female is receptive. The female has a copulatory plug and if she does not become inseminated, she may mate again a month later. One young per female per pregnancy is the norm, two is rare, and gestation takes about seven months. The young weigh about 1 lb (450-490 g) at birth, and have both spines and fur. They grow quickly, doubling their weight in the first two weeks, but remain with the mother at least until the early fall when lactation ends. Juvenile females then disperse, but juvenile males may move in and out of the mother's range for months and even years. They attain sexual maturity at about 1.5 years and typical longevity is of the order of some 15 years.

Theories Of Biological Aging

As witnessed by the search for the fountain of youth and the time-honored popularity of tales and treatments concerned with the aging process, prolongevity has been a continuing quest since the dawn of human history. Although the commercial and health literature abounds with suggestions for staying healthy, looking good, and living as long as one can, the inevitability of corporeal existence is universally recognized. Acceptance of personal mortality does not mean, however, that the human life span cannot be prolonged. But in order to achieve prolongevity, if not immortality, we first need to know what makes us age. Hippocrates was the first medical researcher to study the aging process, which he attributed to a loss of body heat. Erasmus Darwin, a nineteenth-century British physician, considered aging to be due to a loss of irritability in the neural and muscular tissue, whereas Eli Metchnikoff viewed it as being caused by a state of autointoxication, or poisoning by a toxic...

Population And The Social Sciences

Review progress of the relatively new specialty of biodemography which draws on epidemiology, biology, and demography to examine a variety of interesting and important issues, e.g., human senescence, longevity, frailty, and genetic variation. Finally, chapter 22 by Land, Yang and Zeng is devoted to mathematical demography and covers efforts to increase the precision and power of demographic analysis through the incorporation of mathematical models and mathematical statistics.

Red Blood Cell Transfusions

Infectious episodes Iron chelation therapy Patients with longer life expectancy (e.g., 5q- syndrome, WHO subtypes RA, RARS) Initiate after 25 units transfused (500 mg iron) The risks associated with red cell transfusions are considerable, and many may not have been recognized. Increasing recognition of transfusion-transmitted infection drives the search for alternative strategies for the management of anemia. Recent infectious agents considered or proven to be associated with red cell transfusions include hepatitis C, TT virus, and new variant Creutzfeldt-Jakob disease. Although these infections with long incubation times, if transmitted, appear of little relevance to the majority of MDS patients whose life expectancy is 6 years, there are long-term transfused patients for whom the concern for infections is a major issue. Further, red cell alloimmunization is common and the frequency increases with increasing numbers of blood units transfused. Allosensitization may be of particular...

Characterizing Functions Of New Genes

Differential expression of genes from cells derived from diseased tissue versus normal tissue has been used extensively to identify genes that could be involved in disease 16,17 . In one example, differential gene expression was used to identify genes expressed during the aging process. Interestingly, aging induces the expression of stress response genes that can be inhibited by caloric restriction 18 . Although useful to some degree, differential display of expressed genes does not reveal the specific gene or genes implicated in disease, since the expression patterns of genes associated with the genesis of the disease state, as well as of those genes affected by the disease process, are changed. For example, over 300 genes could be differentially expressed in prostate cancer cells relative to normal prostate cells, and still painstaking biological studies on each of these genes could take years to identify the relevant gene(s). In using differential mRNA expression profiles of cells...

Mechanisms of Premature Aging in Diabetes

The clinical and phenotypic similarities between aging and diabetes suggest that there may be shared biochemical pathways leading to the tissue changes. Glucose is the principal metabolic fuel for many animal species. In general, with few exceptions, the plasma glucose level in various animals is maintained within a narrow range (60-140 mg dl). It is possible that the lower limit of blood glucose levels is determined by the minimum tissue requirements of metabolic fuel, and the upper limit defines the threshold beyond which glucotoxicity limits survival of the species (Mooradian and Thurman, 1999b). Avian species, especially owls and parrots, are the exception to this generalization. These animals have high blood glucose levels in the range of 250 to 350 mg dl and yet have a relatively long life expectancy and show no signs of classical diabetic complications. The overall constancy of blood glucose levels across a wide range of animal species suggests that hyperglycemia, except in...

HIV and Cardiac Diseases

New and effective antiretroviral drugs have decreased the mortality of HIV infection. However, antiretroviral therapy (ART) is not without side effects. It is expected that the risk of cardiac and cardiovascular diseases will rise in the following years due to the elevated cardiovascular risk profile and increased life expectancy of HIV-infected patients (Fisher 2001, Neumann 2002a). Therefore, diagnosis and therapy of HIV-associated cardiovascular diseases should become an inherent part of current therapeutic concepts of HIV infection.

Timing Of Testingspecial Considerations

Certain women may choose bilateral mastectomies rather than breast conservation in the setting of a deleterious mutation. In a study by Schwartz et al. (43), 48 of women tested at the time of diagnosis and found to have a BRCA1 or BRCA2 mutation chose bilateral mastectomies for their definitive surgery. These investigators point out that potential advantages to testing prior to completing local therapy are that carriers who choose immediate bilateral mastectomies can avoid a possible second surgery and unnecessary radiation therapy. Disadvantages to this approach include the additional stress of learning about genetic risk for additional cancers, as well as risk for other close family members, at a time when multiple difficult treatment decisions are being made. In addition, clinical testing including the possibility of insurance issues delays may not offer a fast enough turnaround time and could impose unacceptable surgical delay. Some also question the necessity of this...

The Importance of Behavior

The ultimate goal in the investigation of human aging is to extend and improve the quality of life for increasing numbers of elderly. Worldwide fertility rates have declined, coincident with increases in life expectancy, creating a large and expanding bulge at the top of the global population pyramid. In the United States, for instance, more than one in five Americans will be 65 years or older by 2030 (U.S. Census Bureau, 2004), a trend that is fast becoming global and carries immense implications for all world cultures and economies. Moreover, in addition to aging of the general population, demographics within the aged group itself are also shifting as the category of oldest old (80+ years) is growing faster than any other segment of elderly. Now, along with increased longevity provided by scientific achievements, science should also work to increase life satisfaction and happiness for growing numbers of aged. Extended years should be years lived well, if possible. It is our view...

An Evolutionary Framework of Aging

The search for a general, theoretical framework of aging has long been of interest to both geriatrics and gerontology. Before 1900, Weismann proposed the first evolutionary theory of aging and argued that biological aging and death are adaptations that ensure species renewal and are programmed within the organism itself (1889). Mutation Accumulation Theory later explained aging as a process that, due to lessening effects of natural selection on post-reproductive individuals, mutations continue to accumulate over time, increasing mortality in later life (Medawar, 1946). Finally, Antagonistic Pleiotropy describes natural selection as having a bias toward youth that selects against longevity when genes that have pleiotropic effects are advantageous in the young but disadvantageous in the aged organism (Williams, 1957). For an expanded review of these and other proposed evolutionary theories of aging, see Gavrilov and Gavrilova (2002) or Crews (2003). All biological organisms develop,...

Spending Leisure and Other Nonemployment Activities

From conception until death, people are constantly engaged in activities of one sort or another. To be alive is to be doing something, whether it contributes to one's longevity, shortens it, or has no effect whatsoever on how long one lives. Some activities essential or unessential are performed regularly and repeatedly, whereas others occur only occasionally. One activity that takes place quite regularly is spending. Spending can be traumatic, but it can also be enjoyable and even therapeutic. A twist on the saying, When the going gets tough, the tough get going, is the prescription that When the going gets tough, the tough go shopping.

Biomedical Importance

Globally, undernutrition is widespread, leading to impaired growth, defective immune systems, and reduced work capacity. By contrast, in developed countries, there is often excessive food consumption (especially of fat), leading to obesity and to the development of cardiovascular disease and some forms of cancer. Deficiencies of vitamin A, iron, and iodine pose major health concerns in many countries, and deficiencies of other vitamins and minerals are a major cause of ill health. In developed countries, nutrient deficiency is rare, though there are vulnerable sections of the population at risk. Intakes of minerals and vitamins that are adequate to prevent deficiency may be inadequate to promote optimum health and longevity.

Models of Age Related Vision Problems

The visual system provides unique opportunities to study the aging process, as well as challenges in understanding and developing therapies for age-related eye diseases. Exposure of the lens to high levels of photo-oxidative stress and the lack of protein turnover in the lens nucleus make it an optimal system in which to study protein modifications in aging. Similarly, the high level of metabolic activity in the retina and the necessity for turning over large amounts of lipids provide particular research opportunities as well. Finally, visual diseases associated with aging are among the most common threats to the quality of life in the elderly. Of age-related visual diseases, three result in a particularly high burden on the population age-related cataracts, age-related macular degeneration, and progressive open angle glaucoma. Thus, these are dealt with in some detail in this brief review. Because of space and formatting limitations, much work described in this review could not be...

Phase ii clinical trials

With cytotoxics, the generally accepted endpoint for phase II trials is objective tumor response, that is, tumor shrinkage by at least 50 . Tumor shrinkage is not a direct measure of patient benefit, although it sometimes is predictive of benefit. The most commonly accepted direct measures of patient benefit are survival, disease-free survival, and symptomatic relief. Therapeutic effect on these end points cannot be reliably established outside of a phase III trial with an appropriate control group not receiving the experimental therapy. Investigators sometimes like to infer that a regimen prolongs survival because the responders live longer than the nonresponders, but this analysis has long been known to be invalid (4,5).

Energy Balance and Body Composition

And health in the elderly is complex (Wilson and Morley, 2003). A number of recent studies have confirmed that calorie restriction and decreased adiposity are significant determinants of longevity. Although involuntary weight loss is often a sign of illness, there is every reason to believe that regulated and deliberate weight loss in subjects who are obese will lead to health gains similar to those found at a younger age.

Clinical And Economic Outcomes Of Cancer Care 21 Health Care Outcome Measures

Alternatively, clinical outcome can be measured in terms of life expectancy or the average number of years of life remaining at a given age. The life-years of an individual can be thought of as representing the area under the corresponding survival curve (26). The gain in life expectancy or life-years saved with treatment represents the marginal efficacy and can be thought of as the area between the survival curves with and without intervention. This method is more powerful for assessing treatment effect than for comparing median survivals or the event-free proportion at a given time. Changes in life expectancy are often used in economic analyses to express the efficacy of treatment. The major advantage of measures of patient preference or utility is that they can be used to adjust measures of longevity such as life expectancy, e.g., the quality-adjusted life-year (QALY). The QALY represents the time in full health considered by the patient to be equivalent to actual time in the...

Nonwhite Cultures Are Infallible

Another example is Nwadiora's (1996) portrayal of Nigerian families living in the United States. Regarding Nigerians' respect and appreciation for children, Nwadiora reported that Nigerian families are quite democratic when solving family problems and sometimes invite younger family members to express their views (p. 129). Later, Nwadiora writes that children are extremely important, because they ensure the longevity and continuity of several generations, (p. 136). Yet, in the same passage, Nwadiora states, Girls are perceived as sources of potential wealth to families because of the anticipated dowry the bridesgroom will pay. In other words, children particularly girls are commodities to be traded as wives in exchange for money. Nwadiora also denies the extent to which female circumcision is a problem among Nigerian girls by claiming that the practice is extremely rare in Nigerian society and that the much ado in the media about clitorectomy is the result of institutional racism on...

Longlived Monkeys Have Life Spans Proportional To Human Centenarians

Centenarian humans are not out of the scope of primate longevity, especially given the post-reproduction expected from primate patterns. Hammer and Foley (1996) use body and raw brain volume estimates from fossil crania to predict early hominid longevity using a multivariate regression of log body weight and brain volume. Estimates based on regressions ofanthropoid primate subfamilies, or limited to extant apes, indicate a major increase in longevity between Homo habilis (52 to 56 years) and H. erectus (60 to 63 years), occurring roughly 1.7 to 2 million years ago. Their predicted life span for small-bodied H. sapiens is 66 to 72 years. From a catarrhine (Old World monkeys and apes) comparison group, Judge and Carey (2000) predict 91 years when contemporary human data are excluded from the equation. For early hominids to live as long or longer than predicted was probably extremely rare the important point is that the basic Old World primate design resulted in an organism with the...

Research Questions in Nutritional Gerontology

Design of studies in nutritional gerontology. The following sections consider aging research problems in nutritional studies that arise in sampling (including the problem of refusals), variable measurement, fieldwork, statistical analyses, and interpretation. Because this author's principal interest is in cognitive aspects of the associations between nutrients and aging, certain cognitive issues will be alluded to (Kohlmeier et al., 1993). Animal studies are not considered in this chapter, though much of great relevance to human aging has been learned from carefully conducted studies. The topic of animal studies on nutrients and aging is simply too extensive to be dealt with even in summary form in this section. This issue is especially relevant to current studies of the possible benefits that might accrue for general health and longevity through the practice of caloric restriction. Whereas the database from human ecological and animal studies to support the adoption of low calic...

Treatment and Prognosis

Life expectancy is reduced particularly in the case of early onset disease and proximal muscle involvement. The high mortality rate is due to an increase in deaths from respiratory diseases, cardiovascular diseases, and neoplasms, as well as sudden deaths from cardiac arrhythmias.320

The Optic Nerve And Target Intraocular Pressure

In the absence of structural of functional findings on examination of the optic nerve, the clinician certainly must refrain from rapidly advancing therapy to an intolerable or unacceptable level. Nevertheless, advancing optic disk or retinal nerve fiber layer damage even without observable visual field loss is progression and under certain circumstances can be an indication for surgery. Efforts should be directed at estimating the rate or risk of progression. Glaucoma patients who are at highest risk for progression should be identified and the threshold for surgery lowered. Conversely, those glaucoma patients who are at lowest risk should be followed with structural and functional testing of the optic nerve to identify early progression.2 The risk of progression needs to be weighed against the risks and benefits of surgery and the life expectancy of the patient.

Identified health effects

The evidence from accumulated research has enabled the assessment of the health effects of ambient air pollution, including quantitative estimates of the burden of the pollution on a global scale (WHO, 2002) and on individual communities (Medina et al., 2002). These estimates indicate that about 100 000 deaths a year could be linked to ambient air pollution in cities in the WHO European Region, shortening life expectancy by an average ofa year. The number of casualties attributed to air pollution is comparable to the number of fatalities from traffic accidents, and its imprint is observed in all age groups, including children (Valent et al., 2004).

The Operating Biological Framework

Genetic essentialism is a genetic determinism, and, in the case of the Human Genome project seems to involve three central assumptions (1) genotype determines phe-notype (2) genes determine capacity in each person and the boundary conditions established are permanent and unchanging, e.g. intelligence is fixed and non-malleable and (3) genes determine tendencies, both behavorial and physiological or disease tendencies (Strohman, 1996). Three further assumptions manifest themselves in the growing field of genetic medicine, namely, that (1) genes determine diseases (2) genes govern the aging process and (3) genetic analysis provides diagnosis and therapy of disease and aging.

Transgenic Models Of Hypertension

Models transgenic for genes of the endothelin system. Elevated plasma endothelin concentrations have been associated with several cardiovascular diseases, including hypertension. A mouse model overexpressing endothelin-1 gene under the control of its own promoter has been characterized. These transgenic mice exhibit two-fold increases in endothelin-1 concentration in plasma, aorta, heart, kidney, and intestine. Although the blood pressure and kidney morphology and function are normal in young (8 weeks old) transgenic mice, with aging (12-14 months old) they develop renal injury with glomerulosclerosis and interstitial fibrosis (Hocher et al., 1997). In addition, Shindo et al. showed that salt-sensitive hypertension develops with aging in these mice, perhaps secondary to nephron loss (Shindo et al., 2002). This model therefore might be useful for the study of the permissive role of the aging process on the endothelin-induced renal pathology and hypertension. However, there are...

How To Add Ten Years To Your Life

How To Add Ten Years To Your Life

When over eighty years of age, the poet Bryant said that he had added more than ten years to his life by taking a simple exercise while dressing in the morning. Those who knew Bryant and the facts of his life never doubted the truth of this statement.

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