Longevity Health and Wellness Protocol

Grow Younger Blood

Grow Younger Blood is a breakthrough health protocol created by John O'Dowd, Director of the Institute of Longevity. The Grow Younger Blood protocol is so named because you can literally grow younger blood in your body and turn your circulatory health around quickly. Thus, you can prevent and even reverse much of early aging and disease in your body, and be healthier, look and feel years younger, and live better and longer. Heres why: Your blood and circulation affect every part of your body. Your blood provides oxygen, nutrients, and life to every single cell, muscle, tissue, and organ. When your blood is clean, thin, oxygen-rich, nutrient-rich, and your circulation flows freely, your body can function healthily. But when your blood is toxic, thick, oxygen-poor, nutrient-poor, and you also have poor circulation, every part of your body begins to get sick, to age faster, and major diseases begin to occur and grow rapidly. When you transform your blood you transform your health. And thats why this is such a mass appeal product. It appeals and is enormously beneficial to all people worldwide interested in anti-aging, health, and longevity. Read more...

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Basic Methods of the Aging Process

A major advance in biogerontology occurred with the development of techniques to serially propagate cells in culture to senescence. This technique revolutionized biological aging research when it was first introduced in the 1960s. Chapter 2 details the protocols necessary for culturing and subcultivation of normal human diploid fibroblasts. This system appears to be only an approximate approach to understanding the aging process because a direct correlation between cellular senescence and biological aging has been a subject of debate. However, it is through methods such as these that we have learned the vast majority of the molecular processes that contribute to senescence. An important advancement in cellular senescence studies was the development of a reliable biomarker, the senescence associated P-galactosidase (SA-P-gal) assay. This method involves the histochemical staining of cells using the substrate X-gal and distinguishes senescent cells from quiescent cells, an important...

The Genetics of Longevity

One very ambitious program for promoting longevity consists of finding genes that cause or prevent aging and, utilizing the yet-to-be-discovered technology of gene therapy to prevent or promote the expression of these genes, thereby warding off their dire effects or enhancing their salubrious ones. The problem with this technique begins with traditional geneticists' habit of identifying normal genes by their opposite members their mutations. In order to find genes influencing longevity, traditional geneticists look for mutations. In the case of longevity, the relevant mutations would be those that either accelerate aging or extend an individual's lifetime beyond the average life-span for members of the species. The first problem is that On the other hand, several mutations extending an average life-span (among other things) have been discovered in model organisms living in the laboratory.24 For example, in the fruit fly, Drosophila melanogaster,25 the chico26 and methuselah mutants...

High Fat Diets Decrease Longevity in Drosophila

However, the specific mechanism responsible for the deleterious effects of saturated fats is unknown. One of the first studies that attempted to make a connection between Drosophila dietary components and longevity found that isocaloric diets consisting of high saturated fats (such as palmitic acid) and low carbohydrates will, on average, shorten the life span of Drosophila compared with flies fed control diets high in carbohydrates and low in saturated fats (24-26). These early studies, performed in the late 1970s and early 1980s by Driver and colleagues (24-26), did not determine the specific metabolic processes that were negatively affected by the consumption of fat. Instead, they potentially laid the groundwork for further studies. Unfortunately, however, these early studies by Driver and colleagues (24-26) were not followed up by other investigators. Other than dietary restriction, very few recent studies have been done on the effects of diet on...

Games and Competition Longevity and the Individual

Thylation through the influence of specific cytoplasm (maternal, paternal, placental).115 These genes are hardly immortal, changing as they do in every generation. In fact, many genes, including the rapidly mutating genes of viruses, are hardly immortal. The mutations that foreshorten the life expectancy of these genes are sometimes dismissed for a variety of canonical reasons, including definitions of species and the consensus of opinion on the quality of viral life as well as evolution.116 One might not want to rest one's hopes for prolonged longevity on quite so shaky genes.

Longevity Studies With Mated Males and Females

Seven dietary conditions used in this chapter. In the top four conditions, the larvae were raised in control (high sucrose) food. The adults were placed in control, palmitic acid, beef, or soy food for the duration of their lives for the longevity experiments. For the microarray, live weight (LW), triglyceride (TG), and protein level measurements, flies were sacrificed at 10 d (arrow). In conditions five to seven, the eggs were laid in the indicated foods, and the larvae were raised in the same foods (palmitic acid PA , beef, or soy food). Notice that the time from egg laying to eclosion time is longer than in the control food (see Fig. 2). Fig. 1. Seven dietary conditions used in this chapter. In the top four conditions, the larvae were raised in control (high sucrose) food. The adults were placed in control, palmitic acid, beef, or soy food for the duration of their lives for the longevity experiments. For the microarray, live weight (LW), triglyceride (TG), and protein...

Methods for Nutrigenomics and Longevity Studies in Drosophila

Nutrigenomics is the study of gene-nutrient interactions and how they affect the health and metabolism of an organism. Combining nutrigenomics with longevity studies is a natural extension and promises to help identify mechanisms whereby nutrients affect the aging process, life span, and, with the incorporation of age-dependent functional measures, health span. The topics we discuss in this chapter are genetic techniques, dietary manipulations, metabolic studies, and microarray analysis methods to investigate how nutrition affects gene expression, life span, triglyceride levels, total protein levels, and live weight in Drosophila. To better illustrate nutrigenomic techniques, we analyzed Drosophila larvae or adults fed control diets (high sucrose) and compared these with larvae or adults fed diets high in the saturated fat palmitic acid, soy, or 95 lean ground beef. The main results of these studies are, surprisingly, that triglyceride and total protein levels are significantly...

Mapping Genetic Polymorphisms Affecting Natural Variation in Drosophila Longevity

Qtl Mapping Principle

Analyses of mutations affecting life span in model organisms have revealed a number of genes that regulate longevity in evolutionarily conserved signaling pathways. These studies suggest that genes involved in insulin-like signaling pathways, metabolism, stress response, and prevention of oxidative damage influence life span. However, we do not know whether functional polymorphisms at these candidate genes affect population variation in longevity. To identify naturally occurring molecular polymorphisms that are responsible for variation in life span, we must first map the quantitative trait gene (QTG), followed by linkage disequilibrium mapping in a large sample of alleles collected from a natural population. Genome-wide recombination mapping is a well developed approach for identifying the chromosomal regions (quantitative trait loci QTLs ) where the QTGs affecting variation in life span between two strains map. The challenge for this approach has been to resolve the QTL to the level...

Life Extension

As a measure of the potential market for therapies that can actually extend life, according to the American Dietetic Association, about half of Americans used vitamins, minerals, or herb supplements daily in 2000. In addition, according to Information Resources, Inc., 80 percent of sales in the United States are from consumers aged 35 years and older, accounting for vitamin sales of 1.6 billion and herbal sales of 591 million in 2000. Gingko biloba, an herb sold to enhance memory, was the top-selling herbal supplement with 99 million in sales. According to the U.S. National Institute on Aging, despite this spending on antioxidants, RNA and DNA, DHEA, and a variety of hormones, none of these substances provides life extension.

Longevity as a Trait

No claims are generally made for immortality among mammals, vertebrates (other than turtles and tortoises), or most other multicellular animals for that matter, but longevity varies considerably among these organisms and offers many opportunities for contemplating how physiology and evolution collude in the imposition of limits.96 This collusion is not simple or straightforward. First of all, the correlation of size and longevity (exemplified by Sierra redwoods), is problematic when applied to animals. Centimeter-size snails, crayfish, and beetles may live up to 30 years, while the giant clam (Tridacna gigas) of the South Pacific coral reefs, reaching a length of 1.37 m and a weight of 264 kg, has a life span of only about 40 years. The largest living invertebrate, the giant squid, Architeuthis, at four to five years, reaches full size, with a body length of 8 m and tentacles and arms of 22 m when fully extended, at which time it mates and dies (assuming that it follows the pattern of...

Vitalist Health Care

The medical bible of the end-of-century European Naturphilosophie vitalists was the health book by Goethe's friend Christian Wilhelm Hufeland (1762-1836), called Makrobiotik, oder, Die Kunst, das menschliche Leben zu Verlangern (1794), translated into English as The Art of Prolonging Life in 1797 (thus taking the strange foreign word Makrobiotik out of the title).64 Makrobiotik was a handbook on how to control the 'rapid or slow vital consumption' of the life force, and how to regulate the 'vital operations' and 'vital organization' of the body. It held out the hope not only of personally prolonging life, but of being able to perfect it universally, in the future, through physical culture 'by culture alone, man becomes even physically perfect physical and moral health are as nearly related as body and soul. They flow from the same sources become blended together and when united, the result is, human nature ennobled and raised to perfection.'65 There was a new emphasis, in vitalist...

Longevity Research

Possibilities for foiling obsolescence are studied by longevity researchers, and their efforts to push the envelope of life-expectancy outward to its limit have been rewarded. Good health care, especially during one's youth, sufficient nutrition, adequate rest, and time to recuperate from exertion, injury, and abuse have already added years to the average human life-expectancy. One can also buy one or another commodity or service or not buy other commodities or services to good effect. How many more years can be added to the average human lifetime is uncertain, and estimates are all over the map, from no more than 15 years to more than 500 years.15 But death still looms beyond that limit. Prolonged longevity is not immortality it is only postponing the inevitable. Alternatively, a great deal of popular literature offers programs for putting off the inevitable as long as possible, if not indefinitely. The fiction and nonfiction writer, Ben Bova, for example, prescribes a route to a...

Great Ormond Street Series

Homograft conduits implanted between the subpulmonary ventricle and pulmonary artery have made possible the repair of many complex congenital heart defects. Since the first homo-graft was used in a patient with pulmonary atresia and ventricular septal defect by Ross in 1966,1 the operative mortality has declined steadily. However, problems with longevity of homografts were soon acknowledged. Homo-grafts presented by radiation calcified and stenosed early.2 The introduction of porcine valves used in Dacron conduits3 was an important new development. Unfortunately, porcine valves showed accelerated degeneration when used in children.4 In addition, Dacron conduits developed neo-intimal peel which contributed to the development of severe obstruction.Thus, the Boston group reported in 1985 that all their heterograft conduits had to be replaced within ten years of implantation.5 Follow up was 3 months to 22.8 years (mean 5.4 years). Mean age at operation was 6.8 (2 days 28 years). The...

Trygve O Tollefsbol

The aging process encompasses changes at the molecular, cellular, and organismal levels that can be analyzed by a variety of methods. For several decades, a popular mode of studying biological aging has been the analysis of cells cultured in vitro that display cellular senescence. Current interest is also focused on models of senescence that include organismal aging such as aging of yeast and Drosophila. The number of techniques applied to biological aging has increased exponentially over the past decade. Although approaches to biological aging vary greatly, they can be generally grouped into basic techniques, intervention methods, and protocols for analyzing the many molecular and cellular changes seen in aging cells. Hence, this volume organizes the topics into these three categories.

Profile Of The Older Cancer Patient

Aging is associated with reduced functional reserve of multiple organ systems, increased prevalence of comorbidity, memory disorders, depression, malnutrition, polypharmacy and functional dependence 51. It is legitimate to ask whether these conditions may interfere with the treatment of cancer and may reduce the patient's life expectancy and tolerance of treatment to the point that treatment is futile or even harmful. In three studies, cancer patients aged 70 and older had undergone a comprehensive geriatric assessment prior to the institution of treatment, with similar conclusions 52-54 Some form of functional dependence was present in up to 70 of patients, some form of comorbidity in up to 90 , depression, malnutrition and memory disorders in approximately 20 and polypharmacy in 40 . . A review of the Surveillance, Epidemiology and End Results (SEER) data also revealed that some form of comorbidity was present in the majority of cancer patients aged 65 and older 55. These studies...

Apoptosis and Cell Death

Apoptosis (programmed cell death) is characterised morphologically by increased cytoplasmic granularity, cell shrinkage and nuclear condensation. The most prominent feature of apoptosis is the activation of an endogenous endonuclease that degrades nuclear DNA at linker sections to fragments. It has been suggested that a decrease in the rate of apoptosis plays a role in the pathogene-sis and age-related events such as tumorigenesis. Energy restriction increases apoptosis, which may be the mechanism for its effect in suppressing tumours, ameliorating autoimmune diseases, and prolonging life span. Programmed cell death is an endpoint for many cellular events, but it has not been examined in nutrition studies 48 .

Influence of Nutritional Status on Immune Response

A survey of the literature shows that most nutritional deficits lead to suppressed immune responses. This is not surprising, since anabolic and catabolic pathways in the immune system require the same sort of building blocks and energy sources as other physiological activities. Caloric restriction is another area of emerging interest, with important implications for human health. In general, moderate caloric restriction appears to have beneficial effects on longevity and disease resistance. However, these trends and generalisations must be approached with some caution 62 .

Hello Dolly And Salutations To Stem Cells

And then came Dolly, cloning, and stem-cell research, providing, in combination, a cure for mortality This miracle cure does not merely cater to our long-time anxieties over longevity it closes the gap between body and soul, offering for the first time, genuine corporeal immortality

Jeff L Myers and Richard A Hopkins

Historically, comparative studies between valves have centered on the measurement of life expectancy of patients and failure rates of the valves. Difficulties in obtaining reproducible hemodynamic data in the postoperative, closed chest patient have resulted in a reliance on relatively crude measures of function such as the assessment of valve gradients with correlation to subsequent regression of left ventricular hypertrophy. The hemodynamic characteristics of individual valves as they function in vivo are critical since failure rates of the valve are likely related to these properties. Our own in vivo data regarding the energy dissipation of homograft valves in the sheep model demonstrates not only a comprehensive laboratory method for quantifying differences in valves, but also shows critical differences between fresh and cryopreserved valves that may effect long-term results.

Part A Introduction 1 The Aging Brain The Burden Of Life

Increasing life expectancy has raised health problems with respect to normalaging, and particularly to age-related disorders. This holds true for several brain diseases in middle, and more frequently, in old age such as stroke (brain ischemia), Parkinson's disease and dementia of either vascular origin or sporadic Alzheimer type.

Heart Failure in an Aging Society

Two fundamental factors determine the growing prevalence of heart failure in the Western hemisphere average life expectancy and age-adjusted incidence of chronic heart failure (CHF). Since the 1840s the average maximum life expectancy has been increasing at a constant rate of 3 months per year with no change in sight.1 In most industrialized societies the age group over 65 years is the fastest growing proportion.

Cerebral Changes In Physiologic Aging

Lipofuscin Accumulation Brain

Aging is an inescapable natural biologic process affecting all organ systems of the body. This process, regulated by genetic factors (longevity genes) and influenced by environmental factors, begins after age 50 to 60 years or later. Aging of the central nervous system primarily The pathomechanism of cerebral aging is complex. Mitochondria play a central role in the aging process. With advancing age, the amount of mitochondria-derived free oxygen radicals increases, damaging cellular lipids and proteins and the mitochondrial DNA. This oxidative stress is not effectively countered due to a decline in antioxidant defense mechanisms. It is noteworthy that aging increases the risk for neurodegenera-tive diseases, vascular diseases, and malignancies, all leading causes of death in the elderly.

Cardiovascular Mortality

Increased mortality in those who stop athletic activity, who also may have an unhealthy lifestyle. Reduced coronary risk factors and diabetes also have been demonstrated in previous top athletes who continue training.22 Reduced blood pressure also has been shown in previous top athletes still training and in veteran athletes.23 While increased heart size is usually an indicator of reduced longevity, this is not the case in highly trained individuals.5 Comparing different groups of athletes, the biggest reduction of mortality is found in endurance athletes, which may be due to a more active lifestyle after the end of their active careers.

Summary on Preventive Cardiology in Athletes

As there is an increased risk of sudden death during intense athletic activity, a screening including standard ECG should be done in young top athletes in order to prevent sudden death. In middle-aged athletes with a high cardiovascular risk profile, exercise ECG should be performed. There is no evidence of a long-term deleterious effect on the heart due to athletic activity, but there are some data that the prevalence of atrial fibrillation is increased in master athletes. Previous athletes generally have increased life expectancy, reduced cardiovascular risk factors, and a higher level of physical activity. This is most prominent in endurance athletes. Increased life expectancy is limited to those who continue some physical training.

Synopsis And Conclusions

Is the aging brain a burden of life Even after more than 2000 years, Cicero's view is still actual. Aging in general, and aging of the brain in particular may become a burden of life for many human beings. However, although our present knowledge as to how to maintain mental capacity with aging is still limited, new findings at the cellular, molecular and genetic levels open the promising chance to meet one of the most important problems of human society longevity with good mental health.

Ethics Of Dna Testing For Inherited Disease

The applications of recombinant DNA technology are exciting and far-reaching. However, the ability to examine the base sequence of an individual raises important ethical questions. Would you want to know that you had inherited a gene that will cause you to die prematurely Some of you might feel fine about this and decide to live life to the full. We suspect most people would not want to know their fate. But what if you have no choice and DNA testing becomes obligatory should you wish to take out life insurance In the United Kingdom insurance companies are now able to ask for the results of the test for Huntington's disease. This is a fatal degenerative brain disorder that strikes people in their forties. From the insurance company's point of view DNA testing could mean higher premiums according to life expectancy or at worst refusal of insurance cover. There is much ongoing debate on this issue.

Conclusion and Future Directions

HPV causes the most common viral infection of the reproductive tract worldwide. However, the infection is often transient and self-limited. Several studies have suggested that HPV infection and cervical dysplasia can be prevented by HPV L1 VLP vaccines. The licensure of a vaccine against HPV represents a major public health advance against cervical cancer and other less common cancers including those of the anus, vagina, and vulva. Much still needs to be investigated regarding the local immune responses to the vaccine in the lower genital tract, longevity of immune responses, and alternative delivery routes such as intravaginal, intranasal, and oral administration.

Chromatin Versus Other Determinants Of Aging

An intriguing example in this regard is the maternal-effect phenotype of mutations in the C. elegans CLK-1 gene (16). In Drosophila, an unexpected environmental input during development has been observed for flies selected for late-life fitness (13). In this case, the extended longevity characteristic of such flies is not evident unless the larvae are reared at a high density. Numerous examples of alternative life spans encoded by a single genome are cited by Finch (21), but remain at the phenomenological level. Of these, the most striking involves social insects such as honeybees, where alternative developmental pathways, queen versus worker, are associated with 10- to 100-fold differences in life span (21). Third, despite variation and plasticity, senescence can be described as having public versus private components (13). In this context, mechanisms involved in resistance to oxidative and other stresses may apply across multiple taxonomic groups. By contrast, age-related,...

Prostate Cancer Stem Cells A Target for New Therapies

By treating prostate cancer as a disease of epithelium, rather than a consequence of androgen action, it is possible to reconsider its origins. The presence of an initially androgen receptor-expressing (largely luminal) phenotype in tumours has directed research towards the luminal cells as the target for oncogenic change (reinforced by the transgenic mouse studies). Whilst this hypothesis implies that the androgen-independent phenotype is the result of a forced de-differentiation from luminal to more basal characteristics, it is more logical to hypothesise that the basal cell, and indeed the stem cell within that compartment, is the target for the original oncogenic hit(s) and that the resultant phenotype is the consequence of an aberrant but close to normal differentiation pattern. There is now precedent for this in a number of other tumour systems, for example in human breast cancer where the most primitive cell appears not to express the estrogen receptor (Dontu et al. 2004),...

The Cause Of Replicative Senescence Telomere Shortening

Shorter telomeres undergo end-to-end fusions and initiate chromosomal breakage-fusion cycles that cause the cells to undergo apoptosis. There is massive loss of cells from the culture, whereas in replicative senescence (M1) cells do not die, and are in fact more resistant to apoptosis11 . About 1 in 107 cells undergoes an unknown change that permits escape from crisis M2 12. Such a cell line is said to be immortal in the jargon of cell culture, a term that should not be interpreted as implying the reversal of a cellular aging process. In most of these immortalized cell lines the TERT gene has become reactivated 13, but some activate a recombination-based process call ALT (alternative lengthening of telomeres) 14. Although human fibroblasts can form immortal cell lines in this way by escaping from crisis, they never spontaneously immortalize by escaping from replicative senescence M1. Most cancer cells that can be grown in culture are also immortal and express TERT. The mechanisms by...

Role of Apoptosis in CLL

The progressive expansion of CLL in the face of its poor proliferative capacity has led to the notion that the neoplastic cells in this disease enjoy increased longevity owing to defective apoptosis rather than to alterations in cell cycle regulation. Apoptosis, or programmed cell death, consists of a cascade of biochemical events leading to cell destruction that plays a critical role both in normal tissue development and in malignancy (83). The apoptotic failure of CLL has been studied extensively, and numerous mechanisms have been proposed to explain this deficiency. Of course, most investigations have been centered on the Bcl-2 gene family and their proteins (84-86). The importance of the anti-apoptosis Bcl-2 oncogene in B-cell malignancies was established more than 20 years ago in follicular lymphomas with the t(14 18). However, in contrast to follicular lymphomas, translocations of the Bcl-2 gene are relatively infrequent in CLL (87). Indeed, unlike other B-cell...

Aging and Cancer Control

The answer to these questions implies the estimate of the patient's life expectancy and functional reserve, of the aggressiveness of the tumor, and of the availability of effective treatment. Currently, the estimate of life expectancy and functional reserve is based mainly on clinical data, provided by some forms of geriatric assessment, evaluation TABLE 2 Examples of Instruments Currently Used to Estimate an Older Person's Life Expectancy and Functional Reserve 2. Recognition of individuals whose function and life expectancy may be improved by treatment of underlying diseases, social support, management of nutrition, and polypharmacy and physical rehabilitation

Influence of Changes in Bodily Environment on Carcinogenesis

The evidence is accumulating that age is a chronic and progressive inflammation, and the levels of some inflammatory markers, including IL-6, D-dimer, and C-reactive proteins, correlate with life expectancy, risk of disability, sarcopenia, and risk of common geriatric syndromes (10,14,28). The basic question of aging biology is whether chronic inflammation is just a marker of aging or instead is responsible for the manifestations of aging. In other words, is it possible that reversal of chronic inflammation may delay the manifestations of aging, including carcinogenesis From the cancer standpoint, is it important to ask whether

The Team Approach

Measurement of troponin assays has been a tremendous boon to clinical diag-nosis.3-5 Troponins released from heart muscle remain in the bloodstream from 1 to 14 days after onset of AMI, making them the preferred marker for detection of an AMI.2,6-9 Troponins, as cardiac markers, appear to have many advantages primarily due to their quick release following heart muscle damage and their longevity in the bloodstream following the heart attack. However, the methods for analysis have been more of a stumbling block than the utility of troponin for cardiovascular events. Test Methodologies 8-1 and 8-2 describe analysis of cardiac troponin I and troponin T.11,12

Assessment of the Older Person

As shown before, the most important clinical questions related to the prevention and the treatment of cancer in older individuals relate to individual life expectancy and risk of treatment-related toxicity. Current forms of assessment of the older person, listed in Table 2, are not fully satisfactory. Translational research would be extremely helpful by identifying a test or a combination of tests that are able to provide more precise estimates of life expectancy and functional reserve. These may include levels of circulating substances, such as inflammatory markers, genomic and proteomic changes in normal tissues, and imaging tests revealing these changes.

Use in Prevention and Therapy

Chronic diseases and the aging process. Cys-teine and glutathione (by protecting DNA from free-radical damage) may help slow down aging changes6. The amount of glutathione in cells tends to decrease with age. Elderly people may benefit from supplements of cysteine or glutathione to maintain optimum glutathione activity.

Classical Prognostic Factors 21

CLL is the most common leukemia of elderly people in Western countries. The incidence of the disease varies greatly with age. Thus, whereas in individuals younger than 30 yr the incidence x 100,000 yr is less than 1, in those older than 80 yr the incidence x 100,000 yr is about 25. As a result of increasing life expectancy in the overall population and the higher incidence of CLL in the elderly, the median age of patients at diagnosis is now 70 yr, compared with 60-65 yr a few decades ago. However, an increasing number of patients (10-20 ) are being diagnosed when they are younger than 50 because they have undergone numerous analyses for routine or trivial reasons. Studies analyzing the influence of age on the natural history of CLL as well as the prognosis of young patients have been conducted in recent years (5,6). Younger and older patients with CLL show similar overall median survival (around 10 yr), but the causes of death are different (6). Younger patients usually die because...

Lifespan And Maximum Survival

From the perspective of those who study aging, there is an important distinction made between median (life expectancy) and maximum life span. Over the past several decades, with the advent of modern sanitation, refrigeration and other public health measures including vaccination and antibiotics, there has been a dramatic increase in median survival 10. Early deaths have been diminished and more individuals are reaching old age. In the United States today, life expectancy now approaches 80 years 11. Median survival is what concerns public health officials and health care providers but for those studying the biology of aging, it is maximum survival that is the focus of greatest attention. It is worthwhile to note that it has been estimated that if atherosclerosis and cancer were eliminated from the population as a cause of death, about ten years would be added to the average life span, yet there would be no change in maximum life span 12.

Children Elderly Patient

The elderly patient with CHC may be a challenge for treatment. The primary question to answer before treating the elderly patient is whether the HCV infection is going to impact longevity or quality of life. Knowing the approximate time of infection, and the severity of liver disease on liver biopsy, may suggest that treatment is unnecessary in the patient with advanced age. In addition, the elderly patient may have other co-morbidities that make treatment of the CHC inappropriate. However, the decision to treat the elderly HCV-infected patient should be individualized, and not be denied because of age.

Cellular Versus Organismal Aging

Irreversibly arrested growth, a process termed replicative senescence . In fact, it has been proposed that escape from the regulators of senescence is the antecedent of malignant transformation. However, the role of replicative senescence as an explanation of organismal aging remains the subject of vigorous debate. The controversy relates, in part, to the fact that certain organisms (e.g., Drosophila, C. elegans) undergo an aging process, yet all of their adult cells are post replicative.

Paola Fabrizio and Valter D Longo

The chronological life span of yeast, which is measured as the survival time of populations of nondividing cells, has been used successfully for the identification of key pathways responsible for the regulation of aging. These pathways have remarkable similarities with those that regulate the life span in higher eukaryotes, suggesting that longevity depends on the activity of genes and signaling pathways that share a common evolutionary origin. Thus, the unicellular Saccharomyces cerevisiae is a simple model system that can provide significant insights into the human genetics and molecular biology of aging. Here, we describe the standard procedures to measure the chronological life span, including both the normal and calorie restriction paradigms.

Calretinin And Its Possible Neuroprotective Property

A study of the expression of calretinin, together with CBD and PV mRNA, in hamster brain in relation to ageing, has also helped to focus attention on differences between calretinin and other CBPs. Kishimoto et al. (1998) found that whereas CBD transcript levels fell by 50 to 68 , calretinin and PV transcripts remained unchanged. Implicit in these findings is the suggestion that the down-regulation of CBD expression associated with the ageing process might reflect the neuroprotective action of CBD, and further, by inference, that calretinin may not function in this way. However, it ought to be recognised that most of the available evidence is too preliminary in nature to warrant conclusive interpretation.

Late Vein Graft Failure

Coronary artery bypass grafting (CABG) is a procedure that successfully alleviates angina pectoris and increases life expectancy in patients with coronary artery disease. However, the vein graft undergoes adaptive responses to transplantation into the arterial circulation, with early thrombus formation occurring in 10 of grafts, and patency dropping to 50 at 10 yr postprocedure. Vein graft failure is associated with progressive intimal thickening, atheroma development, and neointima formation (96), with associated affects on morbidity and mortality after CABG. Drug treatments (typically antiplatelet agents) can slow and reduce this process, but can be associated with hemor-rhagic events. However, vein grafting is particularly amenable to gene transfer, as the vein graft itself is isolated and able to undergo genetic modification during the surgical procedure. This concept was demonstrated clearly in a clinical trial in which vein grafts transduced during the procedure with vectors...

Treatment of Indolent CLL

This low-risk stage A group this group constitutes almost two-thirds of patients with CLL and has a median age at diagnosis of 64 yr and an expected survival of more than 10 yr, which is close to the life expectancy of a normal population matched for sex and age (9,10). In addition, deferring therapy until disease progression demands it has been shown not to compromise survival (10).

Neal D Kon and A Robert Cordell

Survival is considerably improved with surgical treatment. Expected survival at eight years with either a mechanical heart valve or a stented porcine bioprosthetic heart valve is 80 .4'5 However, these survival curves do not approach normal life expectancy. The reduced life expectancy is multifactorial, but probably involves factors that relate to the presence of a prosthetic heart valve. Prosthetic heart valves may have significant associated problems. The first among these is hydraulic dysfunction. Placing a prosthetic heart valve with a sewing ring inside the left ventricular outflow tract is obstructive.6 The result may be not only a measurable gradient across the prosthetic valve but also a change in flow pattern across the valve from laminar to turbulent. Return to normal left ventricular dimensions is thereby inhibited. Turbulent flow also causes microabrasions and deposition of platelets, which may result in a prosthetic valve more prone to thromboembolic complications and...

Scientific Foundations

In 1999, the National Institutes of Health (NIH) Clinical Organ Transplant Program was formed to develop and test new ways of preventing rejection. The development of new transplantation techniques and better anti-rejection drugs in recent years has helped people with organ transplants live longer. The number of heart- and lung-transplant patients living three years or more after

The Working Draft of the Human Genome

Those hoping to find genes for immortality or even for prolonging longevity must be disappointed with the working draft of the human genome released on February 15, 2001.80 The most up-beat analysis was that of Aravinda Chakravarti who emphasized that For the first time, nearly every human gene and genomic region is marked by a sequence variation.81 Just as soon as a few problems are solved and variation can be studied more efficiently, studies on sequence variations might make it possible to identify the underlying differences in susceptibility to or protection from all kinds of diseases, the age of onset, severity of illness, and responses to treatment. David Baltimore urges caution in evaluating the working draft, since o nly 1.1 to 1.4 is sequence that actually encodes protein that is just 5 of the 28 of the sequence that is transcribed into RNA.82 In other words, the greatest amount of DNA found in the nucleus of human cells still represents a vast secret. WHAT IS AN EVOLUTIONARY...

Central Dogma Of Tumor Progression

Actually be the same genes involved in a selective growth advantage for these cells. These cells maybe lurking even in early-stage cancers. That is, some cancers are predestined almost from the beginning to evolve into invasive, metastatic tumors and some are not. This possibility has huge implications for cancer screening, diagnosis, and choice of therapy. Numerous women receive a diagnosis of ductal carcinoma in situ of the breast based on mammography screening, and many men receive a diagnosis of prostate cancer based on a prostate-specific antigen (PSA) test and subsequent biopsy. And yet many of these patients have indolent tumors that would not affect their overall life expectancy, and they still often undergo significant surgical and drug treatments. The problem is that we are only beginning to be able to tell (e.g., by gene expression arrays) which of these so-called early-stage cancers will be lethal and which ones won't.

MG Hazekamp DR Koolbergen J Braun JA Bruin CJ Cornelisse YA Goffin and JA Huysmans

The fate of the donor cells after allograft implantation has been object of discussion. It has been stated that the presence of viable donor cells after implantation is essential for graft function and longevity. Viable donor cells were believed to play a key role in maintaining the integrity of matrix and fiber structures in the valve leaflets.311 The number of publications contradicting this theory is increasing. Explant studies commonly show little or no cellular-ity.21213 Furthermore, the presumed presence of viable donor cells increases antigenicity, which is thought to be detrimental to allograft function and longevity.13-15

Inhibition Of Synthesis Of Transmitter

Metirosine (a-methyl-p-tyrosine) is a competitive inhibitor of the enzyme tyrosine hydroxylase, which converts tyrosine to dopa as dopa is further converted to noradrenaline and adrenaline they are similarly depleted by metirosine. It is used as an adjuvant (with phenoxybenzamine) to treat phaeo-chromocytomas that cannot be removed surgically. Catecholamine synthesis is reduced by up to 80 over 3 days. It also readily penetrates the CNS and depletes brain noradrenaline and dopamine causing reserpine-like side effects (see above). Hence, in patients whose life expectancy is threatened more by tumour invasion than by mild or moderate hypertension, the need for the drug should be weighed carefully.

The Major Degenerative Diseases

Good health late in life depends largely on avoiding the major degenerative diseases associated with getting old. These common disorders greatly accelerate the aging process -preventing these conditions would allow many to live a healthy life well past the age of 100. (A detailed discussion of the nutritional prevention and treatment of each of these important disorders can be found in later sections.

Implantable Defibrillator

The implantable cardioverter-defibrillator (ICD) has undergone a remarkable transformation over the past 20 years. The early devices were large, requiring thoracotomy for epicardial patch placement, and were implanted in the abdomen. This complex surgery resulted in postoperative hospitalization averaging approximately 1 week. The pulse generators had a longevity of less than 2 years, had almost no diagnostic capabilities, and had pacing capabilities that were limited to only backup ventricular pacing. Modern devices provide detailed information about the morphology and rates of arrhythmias, and store electrocardiographic signals before, during, and after therapy. Heart rate variability and rates are catalogued independent of arrhythmias and lead impedance and sensed electrogram amplitudes (i.e., R-waves and P-waves) are measured regularly and stored in memory. The downsizing of pulse generators, in combination with improvements of lead design and shock waveforms, allows the...

Age And Natural History Of Cancer

The study of the natural history of cancer relies mainly on old reports, of questionable methodology, as in the last twenty years the majority of cancer patients have received some form of antinoplastic treatment. From a clinical standpoint the critical question is whether there are circumstances in which the management of cancer in older individuals may cause worse complications than the neoplasm itself. Clearly, the natural history of cancer is only one aspect of this decision that involves also the life expectancy and the functional reserve of individual patients 41 42. In addition is important to notice that major advances in cancer treatment may have minimized the risk of complications. These include more limited surgery, safer general anesthesia, laser surgery, cryosurgery, radiofrequency tumor ablation, radiosurgery, brachytherapy, conformal field radiation therapy, low dose weakly chemotherapy, and antidotes to chemotherapy-related toxicity, such as hemopoietic growth factors,...

Genetic Instability And Dna Repair

As defined by Foe and collegues (85) may give rise to local pathologies in heterozygous individuals during their lifetimes. As such, mosaicism may underlie defects in proliferative homeostasis and organ pathology that accompany the aging process. For the patient with FA, genetic instability can be seen as a double-edged sword. On the one hand genetic instability implies increased cancer risk, but on the other hand, genetic instability might lead to self-correction and thereby improved bone marrow function. The fact that self-corrected cells emerge in these mosaic patients is highly encouraging with respect to the prospects of gene therapy, since these experiments of nature demonstrate quite clearly that corrected cells can attain an in vivo growth advantage. One of the leading theories of aging is the free radical theory of aging. Many aspects of the aging process can be explained by a gradual loss of endogenous oxygen homeostasis (116). Interspecies comparisons, particularly among...

Puzzles And Perspectives

From a phenotypic view, many of the adolescent and adult patients with FA offer the impression of accelerated aging. These patients mostly are underweight individuals with short stature, a delicate body build, pale appearance, and a hoarse voice. They appear older than their biological age. Survival to age 50 year occurs only in rare instances, and many of the patients surviving to adulthood without bone marrow transplantation may in fact owe their relative longevity to self-correction of bone marrow cells manifesting as mosaicism. There is, however, the puzzle of rare patients with FA who appear phenotypically and clinically normal until adolescence and or adulthood, and who may only be diagnosed when their Symptomatic therapies include steroids and androgens, granulocyte colony-stimulating factor (G-CSF), transfusions, and antioxidant supplementation (153). Gene therapy trials have been conducted with several FANCC and FANCA patients, but success has been difficult to prove (154)....

The Comprehensive Geriatric Assessment

Originally, the answers to these questions were provided by a comprehensive geriatric assessment (CGA), including function, comorbidity, cognition, emotional, social and nutritional status, and medication review 2-3 . Prior to its adoption in geriatric oncology, in general geriatrics, the CGA reduced the risk of hospitalisation and of admission to adult living facilities 4 and may have improved the survival of older individuals 5-6 . In geriatric oncology, the CGA has unearthed a number of unsuspected conditions that might have interfered with the treatment of cancer in the majority of patients age 70 and older 7-9 , has provided an estimate of life-expectancy and of treatment tolerance, and has allowed the institution of a common language in the description of older individuals 2, 10 . Ongoing clinical studies try to derive from the various elements of the CGA an individualised index predicting life-expectancy and risk of toxicity. Table 1 describes the basic elements of the...

The Cardiovascular Health Study and the First Clinical Classification of Older Individuals

Relation to life-expectancy, functional dependence and tolerance of stress Relation to life-expectancy and tolerance of stress Relation to life-expectancy and dependence are predictive of mortality and of chemotherapy-related toxicity 13-14 . In clinical decisions, these parameters should be maintained to identify patients for whom symptom management only is preferred. A subclassification of frailty into subgroups of different life-expectancy and functional reserve is an urgent research project (Fig. 1).

Problems between Cells and Organisms

On the other hand, endless growth is not accommodated in internal organs lacking active turnover mechanisms or access to the external environment, such as the brain and remainder of the nervous system, heart, liver, and lungs, and even most skeletal and smooth muscles. In these organs, a healthy accommodation, whether achieved during normal development or following transplantation, requires restraints on growth. Indeed, the evolution of organisms with internal organs would have to have depended on bringing cellular growth under control, and genes operating in the control of cellular growth are, presumably, old and well-established residents in the genomes of organisms with internal organs. The problem for longevity is that constraints on growth can hardly be set aside in fully grown adults, and precisely these constraints dictate the aging of cells

Presynaptic Da Function

A number of studies have demonstrated DAT binding ligands as effective markers of nigrostriatal dopaminergic degeneration in aging and parkinsonism (30,31). Striatal DAT binding indices decline by 6 per decade in normal controls, reflecting cell loss associated with aging process. DAT imaging reliably differentiates PD subjects from normal volunteers and other PD-like syndromes, and the degree of striatal binding correlates inversely with clinical measures of PD severity (27,28,31). DAT binding in the orbitofrontal cortex also is significantly lower in nondemented patients with early PD and correlates negatively with scores for mentation and depression (29). The reduction in mesocortical or mesolimbic function may contribute to the mental and behavioral impairment observed in PD.

Measuring the Time Between Egg Laying to Eclosion as Adults

In the adult longevity studies, every 2 d the adults were transferred to fresh food in a new cage and the number of dead males and females were counted. The old food with eggs was cut into pieces containing no more than 50 eggs and placed into empty 25 mL vials to determine the fecundity of the parents and to measure the amount of time it takes for the progeny to progress from egg laying to adult. Also, virgin males and females were collected from the vials at least twice a day and kept in separate vials with control food (no more than 20 male or female flies per vial) to determine the life span of these flies. We found that some dietary conditions during larval life affected the life span of the flies. However, these experiments are beyond the scope of this chapter and will be presented at a later time.

Training and Gymnastics

In the fifth century bce the gymnast Herodicus had gained a wide reputation. Herodicus was famed for his command of the training regimen, especially his heroic methods (as practised on himself) of prescribing 40-mile walks, long runs, deep massage, and hot baths. He seemingly tried most things, but what he was most notorious for (according to Plato) was his carefully crafted approach to long-term health care. He was accused by Plato of inventing a longevity health regime for the older male called 'valetudinarianism', or the 'lingering death' an idea to which Plato was scornfully opposed. Plato thought that an honourable life should be quick and natural, rather than slow and artificially prolonged. Hard training was considered necessary for the defence of the state, but unsuitable for the normal, moderate, or temperate life. Normally the most punishing training regimes were reserved for the fit athlete.23 Regular training consisted of set routines of running, ball games, jumping,...

Section 3 alternative translation initiation

The glucocorticoid receptor gene, its products, and their actions represent a paradigm that the expression of different isoforms of any protein resulting from ATI could have physiological and pathological implications. Glucocorticoids interact with GRs (GRs, glucocorticoid receptors), through which they exert their effects. It was found that expression of about 20 of the expressed human leukocyte genome was positively or negatively affected by glucocorticoids. There is the report (Chrousos & Kino, 2005) that the GRa regulates expression of bL-Selection and CD11 CD18 on human neutrophils. Variant mRNA was translated from at least eight initiation sites into multiple GRa isoforms termed GRa.-A through GRa-D (A, B, C1 to C3, and D1 to D3). Recently, a convincing association was made between the ER22 23EK polymorphism of the human GR gene and increased human longevity secondary to a healthier metabolic profile. These polymorphisms were previously found to be associated with subtle...

DNA Repair in Stem Cell Maintenance and Conversion to Cancer Stem Cells

Genomic stability is essential for cell and organism longevity. Without genomic stability, replication errors and external stress as well as direct forms of DNA damage can induce mutations, which decrease cell survival, cause altered gene expression, and can lead to cellular transformation. All represent the antithesis of maintenance of normal stem cell function. We argue here that genomic stability is essential for stem cell maintenance and longevity. This concept is supported by human diseases associated with premature aging and animal models of DNA damage repair abnormalities all of which lead to abnormalities of stem cell survival. Furthermore, with competitive repopulation, hematopoietic stem cell survival can be assessed in the face of DNA repair defects, and results from these studies support the general conclusion that

The Impact of Physical Activity

Considering the high relevance of physical activity and sports for current day social awareness,par-ticipation in physical activity together with healthy peers improves quality of life for children and adolescents. Particularly for them, physical activity and sports play an important social and socializing role. They experience an exclusion from sports and or a restriction of their activity as extremely unpleasant. Accordingly, when asked about their disadvantages in comparison to peers, 62 children and adolescents with CHD put their physical restrictions in first place, even ahead of life expectancy and opportunities for employment.32

Muscle Mass Changes Sarcopenia

Similar to body mass index (BMI), a common definition of sarcopenia accounts for body size by dividing the ASMM by the height squared 44, 50, 51 . In the New Mexico Aging Process Study 45 , sex-specific cut-off points for kg m2 in the ASMM index were set as two standard deviations below the mean for a healthy young-adult population, similar to the definition of osteoporosis. These cut-off points were 7.26 kg m2 in men and 5.45 kg m2 in women. According to this definition, the prevalence of sarcopenia increases from 13-24 among people under 70 to more than 50 among those over 80 (Table 1). Other authors classified their patients as sarcopenic if their ASMM index fell into the sex-specific lowest 20 of the distribution of the index this definition resulted in very similar cut-off values (7.23 kg m2 in men and 5.67 kg m2 in women) 52 . The same authors also measured sarcopenia using the ALM, adjusted for FM and height 52 . The prevalence of sarcopenia according to the first method was...

Methods for Cell Sorting of Young and Senescent Cells

Fell Cell Definition

Cellular senescence, the ultimate and irreversible loss of replicative capacity of cells in primary culture, has been a popular model for studying the aging process. However, the replicative life span of human fibroblasts is heterogeneous even in clonal populations, with the fraction of senescent cells increasing at each population doubling, rather than all cells entering senescence simultaneously. Thus, the study of individual cells in a mass culture is of extreme importance to the understanding of replicative senescence. Cell sorting is a method that allows physical separation of cells with different characteristics when measured by flow cytometry. Here, we describe various methods by which cells that reach senescence early can be physically sorted out of a bulk of growing cells, and discuss how different methods can affect the posterior analysis of the sorted populations.

Gender Differences in Coronary Heart Disease

Coronary heart disease is the leading cause of death and disability among men and women in Western countries. Of the 4 million people in Europe dying every year of cardiovascular disease, 53 are women. In recent decades CHD mortality rates have declined across all age groups among middle-aged and older persons, in a majority of Western countries however, the overall decline rate has been slower in women than in men. The gender difference in CHD mortality has consequently been reduced. Women have a longer life expectancy than men and suffer from clinical manifestations of CHD about 10 years later than men. Younger women have a lower incidence of CHD compared with men the same age, but by age 70 the incidence of CHD is comparable for men and women. This gender differential in CHD incidence is not fully understood. A cardioprotective effect of endogenous estrogens has been hypothesized as the main pathophysiological explanation. In addition, a gender bias among physicians in recognizing...

Overlapping Differential Expression

Found that all three experimental diets significantly decrease longevity, increase the length of time to develop from egg to adult, and alter global gene expression patterns compared with the control high-sucrose diet. Preliminary microarray analyses suggest that a total of 60 genes have significantly (FDR 0.1) altered gene expression diets by all three experimental diets compared with the control diet. The life-shortening effect of palmatic acid confirms previous studies by Driver's laboratory (26). We interpret that time required from egg laying to eclosion as being inversely proportional to the quality of food, at least as it applies to proper Drosophila larval development. If this interpretation is correct, then it suggests that the control (high sucrose) food also has the highest quality. This is not surprising because fruit flies typically lay eggs in rotting fruit, hence their name. Rotting fruits are high in fructose and fermentation products, which like sucrose, are quickly...

Afterword Immortality Triumphant

Now, imagine longevity as a trait capable of evolving into immortality. Substitute the idea of performance advantage for anything resembling purpose or progress, and scale longevity for measurement and appropriate comparisons.127 One might also propose a phylogenetic scenario from comparative data and tease apart an order of events, since a trait may originate with or before a performance advantage (an aptation). What then are the performance advantages of prolonged longevity As already mentioned, the prolongation of average life expectancy might well be paid for by altruistic behavior, including baby-sitting and the banking of cultural knowledge and wisdom. Another problem can be anticipated from the link between prolonged longevity and reduced fecundity the sudden-death syndrome.129 How would a species with reduced reproductive potential due to increased longevity be able to cope with an unanticipated population disaster What were once long-lived birds, the moas of New Zealand, seem...

Palliative Nutritional Endpoints and Decision Making

As an example, a practical approach towards providing nutritional interventions in patients with advanced cancer may include the following elements (1) relative importance of a starvational component (bowel obstruction 5,6 , radiotherapy for head and neck cancers, intake, surgery 7, 8 , high-dose chemotherapy 9 ) (2) probability of a reversible inflammation (infection, treatment-responsive cancer disease) (3) expected life expectancy 10 (4) integrity of the upper and lower gastrointestinal tract (5) goals of the nutritional intervention and meaningful outcomes (6) dietary counselling (assessment of nutritional status, dietary and educational needs, provision of educational and nutritional supplements, alleviate anxiety and conflict around patient's inability to consume what would normally be considered as normal diet) 11 (7) discussion of the option of enteral nutrition in patients with a starvational component and functioning bowel (8) consideration of parenteral nutrition for a...

Age Related Structural Changes

Cardiovascular pathologies such as hypertension and cerebrovascular diseases and heart diseases such as coronary artery disease, arrhythmias, and heart failure increase in incidence with increasing age.2 Age per se is the major risk factor for cardiovascular diseases because specific pathophysi-ological mechanisms that underlie these diseases become superimposed on cardiac and vascular substrates that have been modified by the aging process.3-6 Age-related changes are most likely to be seen in the old-old who have escaped

Age Related Functional Changes

Age-related functional changes are determined by heart rate, preload and afterload, muscle performance, and neurohormonal regulation, all of which may be influenced by age. There is little change in left ventricular systolic function with increasing age, although cardiac output may decrease in parallel with a reduction in lean body mass.7 Increases in heart rate in response to exercise or stress caused by non-cardiovascular illnesses, particularly infections, are attenuated with increasing age.8 Stroke volume increases only by moving up the Frank-Starling curve.9,10 Thus end-diastolic volume increases. These age-related changes in cardiac response to exercise are mimicked by P-adrenergic blockade,11 but P-adrener-gic agonists do not reverse this aging process.12 The decline in exercise performance with age may

Chromatin Perturbations

Heterochromatin also can suppress inappropriate recombination, and thus contribute to overall genomic stability. The best example of how heterochromatin, suppression of genomic instability, replicative senescence, and aging are interrelated is illustrated by the SIR proteins. SIR proteins mediate heterochromatin formation at silenced mating-type and other loci in the yeast Saccharomyces cere-visiae (75). The replicative life span of this single-celled organism is limited in large measure by the accumulation of extrachromosomal circles of rDNA (76). These circles are an indication of genomic instability, as they are produced by inappropriate recombination within the highly repetitive rDNA locus. Loss of SIR3 4 or SIR2 function shortens the life span of yeast, whereas overexpression of SIR2 extends yeast life span and suppresses the formation of extrachromosomal rDNA circles (77). Thus, heterochromatinization by SIR2 suppresses ge-nomic instability (presumably by limiting the access of...

Mark A Lane George S Roth and Donald K Ingram Summary

Caloric restriction remains the only nongenetic intervention that has been consistently and reproducibly shown to extend both average and maximal lifespan in a wide variety of species. If shown to be applicable to human aging, it is unlikely that most people would be able to maintain the 30-40 reduction in food intake apparently required for this intervention. Therefore, an alternative approach is needed. We first proposed the concept of caloric restriction (CR) mimetics in 1998. Since its introduction, this research area has witnessed a significant expansion of interest in academic, government, and private sectors. CR mimetics target alteration of pathways of energy metabolism to potentially mimic the beneficial health-promoting and anti-aging effects of CR without the need to reduce food intake significantly. To date, a number of candidate CR mimetics including glycolytic inhibitors, antioxidants and specific gene-modulators have been investigated and appear to validate the...

Iiintroductory Remarks

The molecular and cellular basis of the aging process is not well understood, particularly in humans, as the scientific community has yet to develop a reliable and predictive set of biomarkers that can be utilized to quantitate specific aspects of senescence within discrete regions and or cell populations. The longevity of a given species depends on several parameters, including frailty (intrinsic vulnerability to death) and senescence (rate of change in frailty over time) 1, 2 . Actuarial rates and survival curves are not particularly useful for predicting aging rates in the brains of mammals. A general consensus is that using surrogate molecular and cellular markers to evaluate senescence throughout the lifespan of animal models is a plausible approach to gain greater insight into mechanisms that underlie aging in humans, with the hope of developing rational pharmacotherapeutic interventions to avoid the scourge of progressive late-onset neurodegenerative disorders and related...

Clinical And Laboratory Features

Long-term follow-up studies have provided valuable information about the outcome of these patients. It is not clear if the life expectancy of this population as a group is changed compared to those without MGUS. Blade et al., in his study of 128 persons with MGUS, did not find any significant difference in the survival probability of persons with MGUS compared to a control population, even though progression to malignancy was clearly associated with a shorter survival.22 In the initial Mayo Clinic series of 241 patients, the overall survival was shorter among those with MGUS compared to an age- and sex-adjusted population.23 Among the 1384 patients from southeastern Minnesota, evaluated at Mayo Clinic between 1960 and 1994, the median survival among those with MGUS was clearly shorter (8.1 years) compared to the expected survival (11.8) for an age- and sex-matched population.13 Among the 1324 cases of MGUS identified between 1978 and 1993 in North Jutland County, Denmark, a twofold...

The Importance of Patient Centred Outcomes

The real value of any cachexia intervention can only be truly measured by assessing the day-to-day impact on the individual patient, whether that be an impact on QoL or patient independence. Over the past 20 years, the importance of such patient-centred outcomes has become evident. Studies have shown that cancer patients receiving palliative care are interested not only in the quantity of their remaining life, but also the quality. For example, in a recent survey of patients with advanced lung cancer, only 22 of patients chose palliative chemotherapy, in preference to supportive care alone, to benefit from the associated 3-month survival advantage 30 . In contrast, 68 of patients chose chemotherapy if it substantially reduced adverse symptoms without prolonging life.

Experimental Models of Caloric Restriction and Applicability to Humans

The lifespan-extending and other beneficial effects of CR, such as anti-tumor effects and the maintenance of more youthful physiology, have been reported in many hundreds of experiments over the past 70 yr. Nonetheless, the question of relevance to humans remains and will go unanswered until definitive human data are obtained (2). There are, however, data from a number of sources that suggest that CR may be relevant to human aging. For example, based on his study of Spanish nursing home residents, Vallejo (3) concluded that reduced caloric intake was associated with a significant reduction in morbidity and that mortality also tended to be lower in the group provided the fewest calories. Caloric intake in residents of the Japanese island of Okinawa differs by 20-40 in adults and children, respectively, compared to the national average (4). Interestingly, Okinawa has a greater proportion of centenarians, a lower overall death rate, and fewer deaths due to vascular disease and cancer....

Caloric Restriction Mimetics

We first proposed the idea of CR mimetics in 1998 (10) and further expanded on this potential approach in a subsequent article in Scientific American (11). In our initial study, we reported that disruption of cellular glucose metabolism (e.g., glycolysis) using the glucose analogue 2-deoxy-D-glucose (2DG) fed in the diet to rats lowered body temperature and fasting insulin levels without significantly reducing food intake over a 6-mo period at the selected dose (10). The 6-mo duration of this study was insufficient to assess indices of biological aging or longevity, but did validate that it may be possible to mimic metabolic effects of CR without reducing food intake. A follow-up survival study in rats unfortunately indicated that the window between efficacy and toxicity was too narrow to make this particular compound useful. The concept of CR mimetics has been further validated in other experiments. For example, similarly to CR, 2DG has been shown to be neuroprotective in rodent...

Psychosocial Aspects and Quality of Life

It is logical to think that the implantation of a life-saving device would make the patient confident of the improved life expectancy and relieve the fear of sudden death. But living with the possibility of receiving a defibrillating shock at any time can be emotionally devastating. Compared to the general population, quality of life and psychosocial adjustment are poor in patients with ICDs.11,12 According to Sears et al., ICD-specific fears and symptoms of anxiety are the most common symp

Impact Of Innovative Technologies In Health Care

As a result of new medicine and technology, patients live longer and want to live better-quality lives (12). The overall elderly population is increasing thus, the health issues related to age also rise. Such diseases as diabetes, stroke, neurological disorders, cancer, and heart disease will be an even more Innovative medicine, along with better education and sanitary and nutritional conditions, will help increase the total population of individuals over 85 yr of age who will live longer and better lives.

High Performance Strong Anion Exchange Liquid Chromatography

A reliable strong anion exchange column for separation of heparin and heparan sulphate oligosaccharides is the Propac PA1 column (Dionex). This column is polymer based and does not suffer from the steady deterioration problems encountered with its silica-based counterparts (short column life, peak broadening and inconsistent retention times). The Propac PA1 column provides the consistent elution times, which are necessary for the disaccharide analysis described earlier coupled with column longevity (consistent over 250 runs in a 2-year period) (12). Sample loads of between 0.5 and 1 mg can be carried out on a 4 mm x 250 mm analytical column, or up to as high as 5 mg on a semi-prep scale (9 mm x 250 mm) column. basic group used for anion exchange (14). The column does not appear to have the longevity of the Propac PA1 column in our hands, requiring re-derivitization after 34 months. This column does however provide better resolution than the Propac PA1 for disaccharides. This can be...

Memory and Concentration Loss

During the aging process the number of functioning brain cells gradually decreases and smaller amounts of neurotransmitters are produced. These changes may impair memory and concentration. However, like most age-associated changes in function, there is great variability in the rate and degree of decline among people. The brain is very sensitive to proper nutrition, and needs a high blood flow and oxygen supply. Poor intake of micronutrients can interfere with mentation and memory and may accelerate functional losses associated with aging.9

Caenorhabditis Elegans As A Model System For Aging Research

Soon the first single-gene mutation (age-1) leading to longer-than-normal life span was identified (8) and subsequently mapped and shown to behave as a single gene (9). Mutations in age-1 are recessive to the wild type and dramatically lengthen life expectancy by an average of about 40 and maximum life span by about 70 (10). These mutants result in a decreased mortality almost 10-fold lower by 13 days of age (11), but have no effect on fertility or development (9). Soon it was recognized that numerous other genes (notably spe-26 12 , daf-2 13 , clk-1 14 , and old-1 formerly tkr-1, (15) ) could also be found to lengthen the life span and slow the rate of mortality (15a). Currently, more than 50 distinct genes have been identified that are directly associated with the aging process (in that altering these genes results in increased longevity see http ibgwww.col-orado.edu tj-lab for an up-to-date list of such mutants ). A number of mutants with shorter life spans also have...

Congenital heart disease

Major advances in surgical approach in patients with CHD have greatly improved life expectancy. Nonetheless, these patients continue to show a higher mortality than healthy subjects over both the medium and long term. Thus, risk stratification of adult patients with CHD could be of help in defining the timing of therapeutic intervention. As in other cardiac diseases, CPET has been introduced in the evaluation of CHD, with great interest in the functional and prognostic information that it can add. Recently, Dimopoulos et al. 82 found, in a cohort of 560 adult patients with CHD, that the Ve-Vco2 slope was the most powerful univariate predictor of mortality in noncyanotic patients and the only independent predictor of mortality among exercise parameters with multivariate analysis in cyanotic patients, however, no predictive parameter was found. This group also followed a cohort of 727 adult patients with CHD for a 28-month period, focusing on the autonomic dysfunction, suggested by an...

Results Risk Stratification

Results of the 651 evaluable patients on NSABP B-20 with corresponding gene expression assays, 64 (9.83 ) developed distant recurrence including 31 (13.66 ) who were randomized to tamoxifen only therapy and 33 (7.78 ) receiving chemotherapy plus tamoxifen. Distant recurrence in the risk score low-, intermediate-, and high-risk patients at 10 years was 3.2 , 9.1 , and 39.5 with tamoxifen alone and 4.4 , 10.9 , and 11.9 for patients receiving chemotherapy plus tamoxifen. The RS-guided therapy is associated with a gain in individual life expectancy of 2.2 years compared to tamoxifen alone for all patients. There was no significant difference in life expectancy at 10 years between the RS-guided therapy and the chemotherapy plus tamoxifen strategies.

Long Life Is Associated With Increased Resistance To Stress

A number of early studies on the long-lived (referred to as age) mutants focused on stress resistance. Long-lived mutants show increased resistance to oxidative stress, heat, and ultraviolet (UV) light (summarized in refs. 20 and 27). A summary of data showing correlations between mean longevity in a variety of mutant strains and subsequent life spans is shown in Figure 1. This information can be supplemented with studies from the Johnson laboratory that are available online (see http ibgwww.colorado.edu tj-lab ) and will be continually updated. Among the various classes of mutants that have been studied for increased stress Figure 1 Correlation between life expectancy and stress resistance. (A) Correlation between relative thermotolerance and life expectancy. (B) Correlation between relative UV resistance and life expectancy. All data are normalized to control for environmental variation by dividing by the corresponding wild-type (N2) life expectancy. Mean life span on agar (life...

Fibroosteat Integration

Single-stage restorative treatments place many of these implant designs into mechanical function during the bone healing period. The interfacial motion could be the primary etiology of this fibrous tissue zone. These types of interfaces have been shown for a variety of designs and materials. Critical to longevity for any material or design is the dimensional stability of this fibrous tissue zone over time (5 to 20 years) and an increase in the thickness of this region is one predictor of clinical failure.

Cholinergic Toxicity

Mechanism Ach Hydrolysis Ache

Hydrolysis of the acetylated enzyme, hydrolysis of phosphorylated enzyme is extremely slow, with a half-life of hours to days. Therefore, the enzyme is effectively inactivated and prevented from carrying out its catalytic function of hydrolyzing ACh. The enzyme molecule phosphorylated with the nerve agent undergoes the aging process (dealkylation) within a few minutes.84 The aged enzyme is no longer reactivated with nucleophilic compounds such as oximes. The physiological, biochemical, and histopathological effects due to cholinesterase inhibition induced by low-dose

Conservative Treatment Modalities

As a result of the reported clinical longevities and the functionalities of several dental implant designs and biomaterials, opinions now reflect the use of implants on a routine basis where they are indicated for dental restoration of normal function. Dental implant-based treatments have moved from the longitudinal research phase in 1970 to a recognized conservative modality in 1990. Important to this change is the quality and quantity of bone and soft tissue available at the time of implant placement, i.e., proper oral diagnosis, plus the significant improvements in dental implant-based treatment systems. This trend is expected to continue to provide ever improved device function and longevity.

Genetic Studies in Aging Brain

The study of aging was one of the original areas tackled by geneticists, as researchers attempted to assess why longevity in humans appears to be a heritable trait. A preponderance of studies concludes that a large proportion variation in the human lifespan can be attributed to genetic variation 80-82 , although specific age-related genes remain at large. Moreover, individual model organisms display significant variance in lifespan, despite the fact that these subjects possess a common genotype and reside in nearly identical environmental conditions 83 . Specific genes contributing to the genetic variation of senescence remain difficult to identify. One approach is to use association studies to compare and contrast aging pedigrees. Association studies typically use population-based genetic screening methods to compare the prevalence of genetic markers between extremely senescent individuals and randomly chosen individuals 84 . Potential markers are then identified by linkage...

The Goals Of Pacemaker Followup Assessment

It remains a challenge to optimize the functioning and longevity of a pacemaker system in the face of constantly changing patient needs, whether those changes are in lifestyle, medical circumstances, cardiac function, or electrophys-iologic milieu. The issue of who should perform pacemaker follow-up evaluations remains an ongoing debate what is clear is that the relevant skills must be continuously and finely maintained.1'2 This chapter explores these issues and examines the methodology of the pacemaker follow-up evaluation.3-6

Caloric Restriction

There are many theories on aging, and one of the most widely accepted is the gradual age-related accumulation of irreparable and irreversible cellular and molecular damage. One environmental manipulation that can alter the aging process is caloric restriction (CR). For example, the lifespan of rodents can be increased by approximately 50 when CR is initiated in young adulthood and maintained throughout life 95 . CR also decreases the incidence of systemic age-related diseases, including cancer, cardiovascular disease, and diabetes in a variety of animal models 96, 97 , making dietary restriction a plausible and relatively inexpensive preventive therapy to consider for aging human populations. CR also has profound behavioral and attentional effects 98 . Moreover, CR in rodents increases neurogenesis in the dentate gyrus 95, 99 and partially attenuates the effects of ischemia 100, 101 and of (MPTP) poisoning within substantia nigra dopaminergic neurons 95, 102 . Thus, CR is an ideal...

Modified Root Replacement Concept Influence of Implant Technique on Allograft Durability

Muscle Implant Concept

Allograft are the best, longest used, and most proven valve commercially available to us. Despite this, less than 1 of aortic valve replacements are performed using the allograft. In part, this is due to a reluctance by surgeons to use more complex surgical methods for aortic valve replacement, even in young people where longevity and complication-free intervals are critical. Other often proffered reasons for infrequent use relate to the perceptions of availability, and the surgical experience or expertise required, as well as what may be an inherent reluctance by surgeons to alter or destroy a normal aortic root in order to replace it with an allograft substitute. Allograft root implantation, however, unlike the original techniques for scalloped subcoronary methods,

Monte Carlo Simulation

Using data from the 1000 Monte Carlo replicates, the mean Standard Deviation (SD) and median incremental cost-effectiveness ratios were US 2769 LYS (US 20,164) and US 1784 LYS, respectively, for RS-guided therapy compared to tamoxifen alone and US 3856 LYS (US 23,106) and US 4198 for chemotherapy plus tamoxifen compared to RS-guided therapy. As shown in Figure 4A, incremental cost-effectiveness ratios for the relationship between RS-guided therapy and tamoxifen alone are primarily represented by an increase in LYS while simultaneously associated with an increase in cost. As shown in Figure 4B, incremental cost-effectiveness ratios for the relationship between RS-guided therapy and the chemotherapy plus tamoxifen strategy demonstrate that the RS-guided therapy reduces estimated total treatment costs in 70 of the randomly drawn samples in Monte Carlo analysis with and an overall benefit in terms of life expectancy.

Choice of Valvular Prosthesis

Status, ability to self medicate, geographical area, opportunity for follow-up, social situation, life expectancy, and contraindication to anticoagulation. Specific valve characteristics to be considered include durability, thrombogenicity, hemodynamics, performance, availability, failure modes and cost. Valvular prostheses can be broadly classified into either mechanical or biological. Mechanical prostheses generally have a greater longevity than biological prostheses, but have the disadvantage of requiring long-term anticoagulation. Warfarin therapy is commonly employed,with a goal of prothrombin ratio of 1.5 to 2.0 (INR 2.0 to 2.5) times normal for aortic position.Antico-agulation with warfarin carries a mortality rate of 0.2 per patient-year and a 2-3 per patient-year of anticoagulant-related hemorrhage. Bioprosthetic valves have the advantage of not requiring anticoagulation, although their are inferior long-term durability makes them a poor choice in certain populations.

Clinical And Biochemical Evaluation Changes Over Aging

The aging process is probably associated with the development of some unavoidable degree of frailty which in the literature is often referred to as normal aging. Even the healthiest octogenarian is more sensitive to the effects of stressors than the healthiest teenager. Diseases and behavioral risk factors contribute to frailty in ways cannot be completely explained by traditional biomedical expectations. The effect of environment on frailty is complex. An environment that is too challenging causes a rapid exhaustion of functional reserves and leads to an overt instability of the biological homeostasis. On the other hand, an environment that is not at all challenging, leads to a progressive atrophy of the homeostatic mechanisms and makes the individual more susceptible to future stressors.

An Initial Interview with an American Indian Client

The African American male has been said to suffer from marginalization in many ways. Franklin (1993) coined the term invisibility syndrome, referring to White culture's fear-based tendencies to treat African males as if they were invisible. African American males have a lower life expectancy than White males or than females of either race because of murder, incarceration, mental and physical disabilities, drug and alcohol abuse, and dangerous employment situations (Hines & Boyd-Franklin, 1996). This invisibility can creep into the clinical interview, either in the form of stereotyped assumptions about the male who is present in the family system, or about the absence of the male in a family system.

Cystic Fibrosis Is A Severe Genetic Disease

Until recently babies with CF did not survive to their first birthday. Today, the life expectancy is 22 years. This remarkable improvement is due to intensive therapy designed to reverse individual symptoms. Digestive enzymes are taken by mouth to replace those proteins the pancreas fails to produce. Physiotherapy helping patients to cough up the mucus in their lungs by slapping their backs reduces the severity of the lung disease. Yet, however remarkable the increase in survival, each life that extends only to early adulthood is still a tragedy.

Oxidative Stress And Aging

The free radical theory of aging has consistently lacked direct, definitive support. This primarily has been due to the failures of many intervention studies. The theory lost considerable standing among researchers during the early 1990s, particularly in the light of the then growing evidence that specific genetic loci can influence the rate of aging in model organisms such as Caenorhabditis elegans. In fact, by the mid-1990s, prominent researchers in the molecular gerontological community voiced the opinion that specific genetic regulatory mechanisms, and not oxidative mechanisms, were the likely place to look for the control of aging, and that antioxidant interventions would never forestall aging. The model that then gained adherents postulated specific regulatory mechanisms rather than entropic processes. More recently still, a synthesis of the two views has emerged, as some of the C. elegans genes implicated in the aging process (sometimes called geronto-genes) have revealed...

Correlations Of Oxidative Stress And Aging

The hypothesis that oxidative stress is a major factor in the aging process has existed for more than 40 years (1). During this period, much correlative data were reported that lent support to the idea that cumulative damage inflicted by endogenous pro-oxidants is deleterious to a cell or to an organism's ability to maintain homeostasis (17). For example, a number of interesting findings have recently been reported in relation to specific protein and carbonyl modifications with age (20,21). In Drosophila, carbonyl modifications have been found to accumulate with aging (22,23). In addition, specific carbonyl modification of mitochondrial aconitase and the adenine nucleotide translocator (ANT) have been reported with age (20,21). In addition to model systems such as Drosophila and the mouse, protein oxidation has been described immunohistochemically in tissue sections of aged human brain in association with lipid peroxidation and proteins indicative of stress (24-27).

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