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. Read more...

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Will Drinking Make One Live Longer

The drinking, those around him or her, and society. But are moderate and responsible drinkers likely to live longer than they would if they did not drink alcoholic beverages The bottom line for epidemiologists is total mortality. We know that, in most prospective studies, the consumption of one or two drinks a day lowers the death rate. We recently had a report from a very large survey (almost fifty thousand people) done by the American Cancer Society on the risk of dying according to alcohol consumption. Total mortality decreased by 21 percent for men and women who reported that they averaged one or two drinks per day compared with that of nondrinkers.

A31 The Mechanism Vitalism Debate and its Implications

Both mechanists and vitalists in the 18th and 19th centuries were committed to 'explaining the cause of life', as opposed to 'considering the effects of life'. The basic distinction between the two camps was simple vitalists posited that a 'vital force' informed living as opposed to non-living matter mechanists held that all components of living matter and all principles underpinning its behaviour were also components and principles of the non-living world. The debate between these two viewpoints is widely, if dubiously, held to have characterised the main conceptual and methodological dichotomy in biology and medicine during this period (Hoernl 1920 Schubert-Soldern 1962 Heim 1972). The appeal of vitalism is readily appreciated. Biological entities are 'endowed with purpose' (Monod 1970), and 'purpose' (Aristotle's entelechy) appears irreconcilable with Cartesian mechanism in which living activities were conceived as 'machine-like'. Indeed, it was not reconciled with any strictly...


We hypothesised that the changes in longevity which we observed could be due to changes in the rate of telomere shortening in tissues crucial for long term survival. Telomeres are nucleoprotein structures at the ends of each chromosome. They serve a number offunctions. It has been suggested that one of these is to control the number of cell divisions which a cell can undergo. In the absence of the enzyme telomerase which appears to be the main but perhaps not sole, method of maintaining telomere length, telomeres shorten with each cell division. When telomeres reach a critical shortness it is suggested that cell cycling is arrested, cell senescence occurs and this may be followed by cell death. The evidence that this process accounts for the senescence of mortal cells in tissue culture is now very impressive reviewed in15. The evidence that telomere shortening may be linked to cell senescence and longevity in vivo is much less clear.

Life expectancy

The life expectancy of women with OSA is shorter than that of men. The cause of this is uncertain, but it may be because of a delay in presentation, a gender-specific susceptibility to endothelial dysfunction in response to repeated episodes of hypoxia, the presence of more comorbidity or poorer compliance with CPAP (see below).

Ontogeny Phylogeny Language and Culture

Our understanding of thinking and reasoning would be gravely limited if we restricted investigation to young adult English speakers. The six chapters in Part VI deal with the multifaceted ways in which aspects of thinking vary across the human lifespan, across species, across speakers of different languages, and across cultures. In Chapter 22, Halford provides an overview of the development of thinking and reasoning over the course of childhood. In Chapter 23, Gallistel and Gelman discuss mathematical thinking, a special form of thinking found in rudimentary form in nonhuman animals that undergoes development in children. In Chapter 24, Salthouse describes the changes in thinking and reasoning brought on by the aging process. The phylogeny of thinking -thinking and reasoning as performed by apes and monkeys - is discussed in Chapter 25 by Call and Tomasello. One of the most controversial topics in the field is the relationship between thinking and the language spoken by the thinker in...

Genome Wide Approaches Using RNAi

The first systematic use of RNAi was in C. elegans. Two groups initially used long dsRNA libraries to target all of the predicted C. elegans open reading frames (ORFs) on either chromosomes I or III (Fraser et al. 2000 Gonczy et al. 2000). Using time-lapse microscopy to view RNAi-treated embryos from fertilization to the four cell stage, Gonczy and colleagues identified 133 genes from chromosome III that were required for meiosis, pronuclear appearance and migrations, spindle assembly, mitosis, and cytokinesis. Fraser and colleagues found 339 genes from chromosome I that gave rise to identifiable phenotypes such as lethality, visible changes (e.g., in behavior), and sterility. Both screens emphasize the power of RNAi reverse genetics, where phenotypes could immediately be associated with genomic sequences without the tedium of, in this case, positionally cloning mutations. In the past few years, RNAi screens in C. elegans have probed phenotypes ranging from genome instability (Pothof...

Future Directions In Esophageal Dilatation

More permanent prosthetic devices such as wall stents are still in their infancy.1 ' Difficulty in placement, higher complication rates, and an unknown longevity make these devices less attractive for long-term treatment of benign strictures of the esophagus.1 ' Technical advances in dilators, such as ones that detect a fall in wall tension or resistance as tissue is dilated, may reduce complications.1 ' 1 ' 1 ' Although dilatation remains the major nonsurgical treatment choice for mechanical and functional esophageal obstruction, only continued comparison to other alternative modalities will allow proper placement of esophageal dilatation in the physician's treatment armamentarium.

Telomeres and Organismal Aging

While the link between telomeres and replicative aging has now been firmly established (de Lange 1998), little is known about the role played by telomeres during the aging process of differentiated cells and postmitotic organisms. Caenorhabditis elegans is an optimal model system to study organismal aging, since this nematode, after passing through its different developmental stages, consists of differentiated cells only. Surprisingly, overexpression of the telomere-binding protein HRP-1 in the worm not only led to elongation of telomeres, but also to an increased life span (Joeng et al. 2004), raising the possibility that telomere length also affects differentiated cells, and in turn, the aging of postmitotic organisms. However, this debate has not been settled yet, since the life span of clonal wild-type nematode strains and of inbred mouse strains is independent of their highly variable telomere length (Hemann and Greider 2000, Raices et al. 2005).

Genome IntegrityDNA Damage Response in Postmitotic Aging

Several pieces of data from C. elegans mutant analysis hint at the idea that genome integrity is indeed essential for the aging of terminally differentiated cells. The soma of C. elegans is composed of a fixed number of exclusively post-mitotic cells, and somatic cells removed by laser ablation or ectopic cell death are not replaced by cell division, resulting in fewer than the standard 959 cells. The worm also contains a fully formed mitotic germ line however, laser or genetic ablation of this organ does not alter longevity (Hsin and Kenyon 1999), indicating that worm longevity solely depends upon the maintenance of its 959 postmi-totic cells. Because of the close correlation among cell cycle checkpoint control and cellular senescence of dividing cells, it was interesting to find that mutation or RNAi depletion of genes required for cell cycle checkpoint arrest in response to DNA damage results in extended organismal longevity of the worm, which is composed entirely of postmitotic...

Future Uses Of siRNAS

The ability to remove or decrease a specific target gene using siRNAs has been exploited in C. elegans to create a siRNA library that can be used to analyze the phenotypes of almost every gene in C. elegans. C. elegans undergo RNAi when fed bacteria producing dsRNA.97 Julie Ahringer's laboratory has created an RNAi feeding library of bacterial strains that produce dsRNA against 86 of the C. elegans genome ( 16,500 individual bacterial strains, each producing dsRNA against one specific gene).9899 A number of laboratories have used this RNAi feeding library to systematically analyze the represented genes for loci that are involved in numerous aspects of development. For example, this library has been used to screen the C. elegans genome for genes involved in fat regulation, chromosome stability, longevity, and embryonic development.98 100-103 The ability to quickly screen through a large portion of the entire genome of an organism for a specific phenotype is extremely powerful. Other...

Telomeres Senescence Oxidative Stress and Heterogeneity

Abstract Life span heterogeneity is a hallmark of the ageing process. It is also a characteristic feature of telomere-dependent replicative senescence. We review here evidence showing that telomere shortening is heterogeneous between telomeres and between cells, and relate this to cell-to-cell variation in mitochondrial function and production of reactive oxygen species (ROS). Telomere shortening is to a large extent governed by ROS-mediated telomeric DNA damage, and we show here that apparently stochastic variation in mitochondrial ROS production can account for vast differences in replicative potential between individual cell lineages.

Chronic Hypertension High Blood Pressure Is Caused by Impaired Renal Fluid Excretion

Even moderate elevation of arterial pressure leads to shortened life expectancy. At severely high pressures mean arterial pressures 50 per cent or more above normal a person can expect to live no more than a few more years unless appropriately treated. The lethal effects of hypertension are caused mainly in three ways

General Characteristics

Therefore, permits a more accurate picture of worldwide prevalence. Type II DM is a chronic disease with generalized symptoms therefore, many cases are not diagnosed. However, rates of type II do appear to be increasing in developing nations. Generally, investigators have been cautious in interpreting an actual increase in the incidence of insulin-dependent DM. Prevalence rates continue to rise because of increased longevity of individuals with type I diabetes. Incidence rates for type II diabetes vary extensively by age and sex for different populations. In general, the incidence increases with age for both males and females until the sixth or seventh decade of life.

Telomerase and Ageing

While accumulating evidence has supported the notion that telomerase insufficiency leads to telomere shortening and replicative senescence of cultured cells, the role of telomere maintenance in the ageing process has not been clear. Ageing as a physiological process or phenomenon is characterized by impaired response to stress, unbalanced homeostasis, and increased risk of disease (Weinert and Timiras 2003). The relevance of telomere shortening induced by dysfunctional telomerase to physiological ageing was first demonstrated by the generation of a mouse model devoid of telomerase activity (Blasco et al. 1997). It was observed that late-generation mice deficient for telomerase had a shorter life span than wild-type mice. In addition, although early generations of mTR- - mice did not show abnormalities (laboratory mice have a much longer telomere length than humans or wild mice, and telomeres only become critically short after several generations with no telomerase (Herrera et al....

Similarities and Differences Between DC and Ageing

As mentioned above, DC patients have a median life span of 16 years, while some can survive up to 50 years old and milder cases even longer. The shorter life span in DC patients could be inferred to be the result of dysfunctional telomerase. The death of DC patients is usually caused by complications of bone marrow failure (immune deficiency or bleeding), pulmonary fibrosis, or malignancies. These are extreme examples of some of the organ or tissue dysfunction that takes place in normal ageing. Perhaps a key feature of the disease process in DC is that it involves the failure of some tissues, principally highly proliferative tissues that are dependent on renewal by stem cell activity. Ageing, however, can affect the entire organism. Nevertheless, in the first generation of mice carrying a deletion of mTR, when no hematopoietic disorders were apparent, the longevity was reduced in comparison to wild-type mice (Geserick and Blasco 2006). This observation supports a role of telomerase in...

Telomerase and Cancer

Fig. 5.5 Model of the pathogenesis of dykeratosis congenita and ageing. (A) X-linked DC and DKC1 gene mutation. (B) AD-DC and TERC gene mutation. (C) AD-DC and TERT gene mutation. (D) Ageing. Mutations in multiple components of the telomerase complex are identified in patients with dyskertatosis congenita, suggesting that excessive telomere shortening is the underlying cause of this disease. (A-C) The critically shortened telomeres lead to cell cycle arrest and or cell death in rapid dividing cells including stem cells and early progenitor cells. The cell senescence death results in the recruitment of more stem cells into cell cycle. Consequently, the increased proliferation of a decreased number of stem cells aggravates the rate of telomere shortening, which ends up with the depletion of the stem cells and the development of disease phenotype. Mutations in TERC or TERT directly reduce the enzymatic activity of telomerase and disrupt its function in telomere maintenance (B and C)....

Maintaining the HSC Population Stem Cells Make Life or Death Decisions

In addition to factors that influence HSC self-renewal decisions, factors that regulate cellular death and senescence also play an important role in maintaining stem cell homeostasis and may thereby account for differential ageing patterns observed in various inbred mouse strains. Cellular ageing is associated with the accumulation of DNA damage and genomic instability, and it has been hypothesized that proteins regulating DNA-damage response pathways are key regulators of ageing (Dumble et al. 2007). For example, p53 is a tumor suppressor protein that is activated in response to cellular stresses, including DNA damage and oncogenic activation, to induce cell cycle arrest or apoptosis or both. Mice expressing a hyperactive p53 protein display a heightened tumor resistance and, surprisingly, significantly reduced longevity compared to wild-type mice (Tyner et al. 2002). The mutant mice display a generalized organ atrophy and reduced stress tolerance at middle age that progresses with...

Signaling Pathways Implicated in Cell Intrinsic HSC Ageing

Transplant, the ATM-'- HSCs showed an elevation of ROS and an increase in p38 MAPK pathway activation compared to wild-type. These data are consistent with the hypothesis that stem cells are depleted during the normal ageing process due to an accumulation of ROS, leading to an increase in p38 MAPK signaling, which in turn results in an increase in cell cycling without the critical function of self-renewal (Ito et al. 2006).

Who Will Be The Judges

Li, in his presidential address to the American Society of Human Genetics in 1960, pointed out the real fallacy in eugenic arguments. Man has continuously improved his environment to allow so-called inferior individuals to survive and reproduce. The movement into the cave and the putting on of clothes protected the individual unable to survive the stress of the elements. Should we then consider that we have reached the peak of man's progress, largely determined by environmental improvements designed to increase fertility and longevity, and that any future improvements designed to permit anyone to live a normal life will only lead to deterioration Nineteenth-century scientists, including such eminent biologists as Galton, firmly believed that this peak was reached in their time. This obviously fallacious reasoning must not allow a lapse in ethical considerations on the part of the individual and by humanity as a whole, just to placate the genetic pessimists.

HSCIntrinsic Mechanisms of Functional Decline Lead to Changes in Stem Cell Number with

Stem cells in the relatively long-lived C57BL 6 (B6) mouse strain increase in number during ageing, whereas stem cells in DBA 2 (D2) and BALB cBy (BALB) strains decrease over time and display overt signs of ageing (Morrison et al. 1996, Chen et al. 1999, de Haan 1999, Kamminga 2005, Yuan et al. 2005). When equal numbers of bone marrow cells from old and young B6 mice are mixed with heterogeneous competitor cells and injected into lethally irradiated recipients, the old cells have a competitive advantage compared to young cells (Harrison et al. 1989, Morrison et al. 1996). In stark contrast to these results, old stem cell populations in the relatively short-lived D2 and BALB mice display a significant competitive disadvantage compared to young cells (Harrison et al. 1989, Van Zant et al. 1990, Chen et al. 2000). Strain-dependent differences in B6 and D2 stem cell ageing were demonstrated in a series of experiments in allo-phenic (cellular chimeras) mice....

Treatment Options for Unresectable Disease

For patients proceeding to surgery with the expectation of resection but who are found to be unresectable due to metastasis or locally advanced disease, a number of options are available. Some authors advocate palliative resection with transhiatal esophogectomy whenever possible. Others argue that whatever the morbidity, resection is hardly justified for a disease with such poor life expectancy at its advanced stages. The potential for endoscopic dilation, laser or radiofrequency ablation with dilation and stenting, and radiation with or without chemotherapy in the patient found to be unresectable are recognized options. The choice is usually determined by institutional capability, as there is no evidence favoring one treatment over another in terms of overall improved survival.

Stem Cells and Cancer

We have noted that adult stem cell populations exhibit functional decline with age. Ageing is also associated with a dramatic increase in the incidence of cancer, and several recent studies support a stem cell origin for cancer (Campisi 2003, Campisi 2005, Kaplan et al. 2006, Li and Neaves 2006, Rizo et al. 2006, Li et al. 2007). Together, these findings offer strong support to the stem cell theory of ageing by connecting functional decline in the stem cell population to malignancy resulting in limited organismal longevity. Interestingly, from the cell surface, stem cells from a variety of tissues resemble their malignant counterparts. Hematopoietic, mammary, neural, lung, skin, and prostate stem cells can be identified by some of the same cell surface markers used to identify cancer stem cells in these tissues (Li et al. 2007). In addition to cell intrinsic similarities between normal stem cell and cancer cells, an enormous body of literature describes intricate relationships between...

Seasonality and variability in life cycles

Variations in aquatic insect life history traits among three basic types of temporary water are modelled (based on Stearns 1976) in Figure 5.2. This interpretation is preliminary in light of the limited empirical data available, but it is presented both as a platform for critical re-examination of the application of r-K selection theory to the inhabitants of temporary waters and in the hope that it will stimulate further research. The loss of water in all three waterbody types is seen as providing sufficient selective pressure for commonality of traits such as egg diapause, however, while some r-selected traits (e.g. good powers of dispersal, medium to high fecundity) benefit inhabitants in all three types of water, there is discrepancy in the perceived selective advantage of others (e.g. longevity). Indeed, in some cases (e.g. growth rate and pattern), opposing traits seem to apply, but then Pianka (1970) has argued that no organism is

Telomere Dynamics in Mature Hematopoietic Cells

Division and clonal expansion are critical for effective immune function, telomere dynamics are of particular interest in these cells. Again, limited telomerase levels are not sufficient to prevent telomere shortening and replicative senescence. However, overexpression of hTERT is able to reconstitute a constant high level of telomerase activity and extend the life span of T cells (Hooijberg et al. 2000, Rufer et al. 2001b). Although the rate of telomere shortening is lower in hTERT-transduced T cells, long-term studies indicate here a progressive telomere loss eventually resulting in even shorter telomeres at senescence than in controls (Roth et al. 2005). Interestingly, elimination of endogenous hTERT in human T lymphocytes using a dominant-negative mutant (DN-hTERT) leads to a decreased life span and cytogenetic abnormalities, which indicates the major influence of hTERT on the longevity of these cells-without preventing overall telomere shortening but maybe playing a role in the...

Conclusions and Outlook

Hematopoietic stem cells maintain hematopoiesis through tightly regulated layers of self-renewal, differentiation, and cell death during the entire life span of vertebrates. Nevertheless, programmed telomere shortening as a hallmark of replicative senescence occurs in HSCs, which is not completely understood, since conventional correlations between telomere maintenance and telomerase activity appear to be only partially valid in these cells. Importantly, telomerase activity and telomere dynamics seem to play a different role in embryonic stem cells compared to adult stem cells. Although stem cell proliferation generally allows for tissue repair and regeneration, it also bears the risk of cancer, which is impaired by tumor suppressor mechanisms, either eliminating potential cancer cells by apoptosis or limiting their proliferation by senescence. Apparently, factors ensuring stem cell proliferation as a prerequisite of relative longevity must be well balanced with mechanisms that...

Imprinted Genes As Cancer Susceptibility Loci

Human IGF2 has four promoters that function in a tissue-specific manner (Vu and Hoffman, 1994). Promoters 2 to 4 are contained within a CpG island, and transcripts derived from these promoters are monoallelically expressed. In contrast, the P1 promoter 20 kb upstream of P2 is not associated with this CpG island, and drives biallelic expression of IGF2 in the liver (Vu and Hoffman, 1994 Baylin et al., 1998). During the ageing process, the P2 to P4 promoters of the normally unmethylated paternal allele are subject to incremental increases in methylation, and methylation of these promoters is also enhanced in cancer. Hypermethyla-tion of this region in tumour cells results in decreased expression originating from the P3 promoter with the switching of IGF2 transcription regulation to the non-imprinted P1 promoter (Vu and Hoffman, 1994). The ability of IGF2 to undergo such promoter switching can be regarded as an epigenetic mechanism by which tumour cells can gain a selective growth...

Genetic and ethical considerations

A central aspect of reproductive counselling in people with CF is the consideration of the reduced life expectancy of the parent with CF and the resultant emotional, financial and psychological effects (Tonelli 1997). The prognosis of the affected parent needs to be discussed objectively with both partners to ensure that both are fully informed. In many countries, the age that women are having their first child is now older than in previous generations. This has significant implications for young women with CF whose lung function generally worsens with age.

Stem Cell Function Declines with Ageing

As extensive tissue replacement does not occur in adults of short-lived invertebrates, such model systems have to date been less useful in understanding the mechanisms of stem cell ageing. A notable exception in this regard, however, have been the elegant studies of germ line mortality genes by Ahmed and colleagues (see, for example, Ahmed and Hodgkin 2000, Meier et al. 2006), which have identified several pathways required for germ line stem cell longevity, including maintenance of telomerase. Nonetheless, the bulk of studies of the determinants of stem cell longevity have been carried out in rodents, with confirmatory analyses in humans where possible. Of these rodent studies, the majority in particular have focused on hematopoietic stem cells in mice, which are the most well-characterized tissue specific stem cells.

Hematopoietic Stem Cell Ageing

With ageing, and a correlation between stem cell expansion and longevity has been suggested (de Haan et al. 1997, Henckaerts et al. 2004). Thus, it is possible that genetically outbred mice in the wild would exhibit more pronounced stem cell attrition upon greater exposure to environmental stresses that are not normally encountered by laboratory-housed strains under experimental conditions optimized for longevity and easy breeding.

Mitochondria and Reactive Oxygen Species

The important role of redox signaling in the regulation of physiological responses is underscored by the apparent dysregulation of physiological responses in various disease-related oxidative stress conditions. Excessive levels of reactive oxygen species (ROS) may be generated by mechanisms that produce ROS accidentally in an unregulated fashion. This includes the production of ROS by the mitochondrial electron transfer chain, the quantitatively most important source of ROS in higher organisms. These chemical species are characterized by the presence of an unpaired electron on the oxygen atom that can promptly react with virtually any biomolecules. Thus, mitochondrial structures are particularly susceptible to oxidative damage as evidenced by lipid peroxidation, protein oxidation, and mitochondrial DNA mutations 11 . ROS have been implicated in many pathological conditions, in particular in the aging process. Indeed, the free radical theory of aging has a long history and it has been...

The Proliferative Stage

Osteoblast-osteoclast renewal is essential to sustain the dynamics of bone wound healing over an 8- to 10-week period. Neither osteoblasts nor osteoclasts are immortal. Osteoclasts have a life expectancy of about 2 weeks. After approximately 4 weeks, most osteoblasts undergo apoptosis (cell death), although a small percentage become cells that line the trabeculae and others become embedded within the calcified matrix to become osteocytes. The continual cell source for osteoblasts has been localized to bone marrow stromal cells and blood vessel pericytes. The former have adipogenic and chondrogenic potential, the lineage being determined by the quantitative availability of specific BMPs (39,40). Molecular lures for pericytes, preosteoblast cells from endosteum, periosteum, and marrow may include fragments of collagen and breakdown products at the fracture. Additional molecules providing chemotactic signals for cells to the fracture site include osteocalcin, bone sialoprotein, and...

Spinocerebellar Ataxia Type

Management, Prognosis, and Future Perspectives. At present, there is no specific treatment for patients with SCA5. Symptomatic and palliative therapy is similar to that described for SCA1. Although SCA5 is disabling, the disease progresses slowly, and life expectancy is not shortened. Quantitative data about the rate of progression in SCA5 are not available. At present, the chromosomal localization of the SCA5 gene is known. To further understand the pathogenesis of SCA5 and to develop diagnostic tests, the SCA5 gene must be cloned and the mutation identified.

Variable Stimulation Of The Immune System Of Primates Under Different Conditions

History of a retrovirus in any new primate host. Consequently, it can be argued that the AIDS virus may well have been adapted to be gentle and virtually un-obstructive in an old host, but at present in humans, those strategies do not work the same because the human pathogenicity is different. Because of our social organization, our life expectancy, and our antigenic environment, the outcome of this parasitism could well be quite different. Possibly the finding is relevant to the case of an individual that became infected with only one strain even though two different varieties of HIV were transfused simultaneously into him (Diaz etal., 1996).

Plastic or Metallic Stents

Based on previous considerations, for choosing the right stent it is essential to consider the life expectancy of the patient. Patients with unresectable carcinoma without signs of distant metastases and with a life expectancy of 6 months or more benefit more from a metallic stent conversely, in patients with unre-sectable disease and hepatic or distant metastases with a short prognosis (

Adult Small Intestinal Stem Cells Identification Location Characteristics and Clinical Applications

Have been performed on this dynamic process (Qiu et al. 1994 Winton et al. 1998 Winton and Ponder 1990 Wong et al. 2000). Such studies have enabled the migratory pathways to be mapped, the velocity of the cell movement to be determined and the stem cell lineages to be identified. Cells move as vertical columns, at least once on the villus, where they move with a velocity of between one and two cell diameters per hour (Kaur and Potten 1986). As a consequence of this migratory activity, new cells born in the upper region of the proliferative zone of the crypt of the mouse reach the tip of the villus in about 3 days, which represents their total life expectancy in the tissue. Cells born from lower in the crypt may have a life expectancy of about 5 days. Thus within 3- If the stem cells in the small intestine of a mouse cycle once a day, this means that in the life span of a laboratory mouse, which might be 3 years, these cells divide a thousand times a very large division potential. This...

Opinion of the Group of Advisers on the Ethical Implications of Biotechnology of the European Commission

From the point of view of basic research, this result is important. If repeatable it may allow greater insight into the aging process, how much is due to cell aging, and whether or not it is reversible. Such work may also increase our understanding of cell commitment, the origin of the cancer process, and whether it can be reversed, but at the present time the research is at a very early stage. Dolly may have a shortened life span or a greater susceptibility to cancer if she is fertile, her progeny may show an increased abnormality rate, owing to the accumulation of somatic mutations and chromosomal damage.

George J Chang Mark L Welton

The immunocompromised state is characterized by defects in the system of defense against infections and malignancy and is classified as primary (as in immunodeficiency syndromes) or secondary (as in acquired states). Impaired immune function may thus result from genetic disorders, malnutrition, injury, disease, cancer therapy, inflammatory diseases, or pharmacologic manipulation. Advances in transplantation, oncology, and the treatment of acquired immune deficiency syndrome (AIDS) have increased the life expectancy of these patients, and thus the population of patients with impaired immunologic function has enlarged. Immunocompromised patients who have problems that require surgical attention are more likely to experience a delay in diagnosis and an increased mortality rate compared with patients without immune defects. Because an increasing number of surgical patients are immunocompromised, it is important to recognize and to understand the immunocompromised state to properly manage...

Are Chondrocytes the Best Cells to

Joints repaired by stem cells were still intact at that time.90 As the longevity of the repair of cartilage defects is under question, it may be worthwhile examining the role of stem cells in cartilage repair, as stem cells or progenitor cells may in fact differentiate into chondrocytes which may produce a long lasting repair.

Unrelated Future Costs

In cases where an intervention is life-saving, those individuals will incur unrelated health care costs in the future. For example, a woman having had a hysterectomy for local carcinoma at 55 years with no relapse will have a life expectancy equal to that of the general population and will also incur health care expenses over her remaining life-time similar to that population.

Cross Sectional Versus Longitudinal

In this particular circumstance, only one age and only one ejection fraction were measured as a snapshot of each patient. This cross sectional evaluation permits an examination of differences in ejection fraction between people of different ages. The longitudinal perspective examines the effect of the aging process in single individuals.

Biogenesis Of Ubiquitin Protein Inclusions Aggresomes

It is unclear why neurodegeneration associated with hereditary forms of neurodegenerative disorders only becomes symptomatic in the adult or at an advanced age despite the congenital presence of specific mutant proteins. Zanusso et al121 postulate that the ubiquitin proteasome pathway degrades mutant proteins shortly after they are produced, thus preventing their aggregation. Malfunction of this pathway caused by harmful conditions, such as oxidative stress or inflammation, may mediate a decrease in the degradation rate of abnormal proteins, bringing about their accumulation as protein aggregates which may form inclusions. An aging-induced decrease in proteasome function may also contribute to stabilization and aggregation of mutant proteins that are normally turned over by the ubiquitin proteasome pathway. A micro-array analysis of the expression of 6347 genes in mouse skeletal muscle revealed age-dependent decreases in the expression of genes encoding stress factors and proteins...

Home and community care

Local responses involve people in their homes, neighbourhoods and community organizations. They take responsibility for addressing HIV AIDS as a shared community concern. Community interventions to support PLWH should include supporting TB patients to complete treatment. Some PLWH regard TB as an ominous sign of AIDS.A more optimistic view of the development of TB is as an opportunity to seek help for a treatable condition.The prospect is of an increased healthy life expectancy. Targeted information, education and communication interventions can encourage the more optimistic view.

A1 The Two Approaches to Medical Biology

We have argued that it is desirable, and possible, to bring together the 'mechanistic' and 'pathophysiological' ('vital-materialist') approaches to medical biology. However, because our account of DVT-related research has been largely historical, we have emphasised their divergence during the course of this book. In particular, we have stressed (1) the schism that separated the two approaches during the 1840s and (2) the overwhelming dominance of the mechanistic approach during the last half century. In this appendix we shall attempt to explain these two historical observations. We shall also explore why vital-materialism (the pathophysiological approach) is sometimes confused with vitalism. standpoints in religion, politics, science and other aspects of culture.) By implication, the physician pathologist surgeon's knowledge and experience are ranked lower than those of molecular biologists.1 Yet molecular biologists do not first encounter, for example, DVT in clinical practice and...

Adenocarcinoma of the Oesophagus

Disordered cell growth, called dysplasia, constitutes the first step in the progression of Barrett change into cancer. Dysplasia is recognized by the appearance of an increased nuclear--cytoplasmic ratio and loss of nuclear polarity. Initially, the metaplastic glands are lined by cells that become pseudostratified, somewhat resembling colonic adenomas. As the degree of dysplasia progresses, the cells become increasingly disorganized and the nuclei lose their pseudostratified appearance. Invasive cancer becomes recognizable once the tumour cells extend through the muscularis mucosae into the underlying submucosa. The evolution from low-grade dysplasia through moderate- to high-grade dysplasia and invasive cancer is shown in Figures 17 and 19. Overall, many invasive tumours appear to be very well differentiated because they make clearly identified glands. Other tumours are poorly differentiated and it is difficult to identify glandular structures. Even well-differentiated tumours have...

Evolutionary Considerations

Constant stimulation is not new our increasing life expectancy is. Tissue declines with age. Rousseau (1762) asked the question, Why are men in chains when they are born free Perhaps an analogous question is, Why is there so much worry when we have so much One reason is that if we don't find worry, we are very good at constructing it. This is not just a piece of pathology.

Primary Central Nervous System Lymphoma

PCNSL (see C.ha.p.teL4.6 ) develops in approximately 5 percent of patients with AIDS and is found at autopsy in up to 10 percent of cases. It is the initial AIDS-defining illness in 0.6 percent of adults. Primary CNS lymphoma develops in patients with advanced HIV-1 disease who are severely immunosuppressed. Ihe incidence of PCNSL in the AIDS population may be increasing as longevity is extended by medical management and antiretroviral agents. Lymphomas are usually of the diffuse immunoblastic, or diffuse large cell, or small-cell noncleaved B-cell type ' J with a predilection for the deep cerebral gray matter, corpus callosum, periventricular white matter, and cerebellar vermis. A relationship to EBV is strongly suggested. EBV is frequently detected in the tumor tissue and detection of EBV DNA by PCR in CSF is sensitive and specific for establishing a diagnosis in the appropriate clinical setting.

A28 The Opening of the Schism

Vital-mechanists' primary concern is not the 'cause of life' but the effects of life - they are concerned with what living matter actually does because it is living (as opposed to non-living or dead).13 Under the influence of Naturphilosophie, 19th-century vital-mechanists became interested in principles of organisation and 'harmony' that were peculiar to biology. They were sceptical about extreme mechanistic views, just as Goethe and others were sceptical of Kant, but this did not commit them to vitalism, as is sometimes alleged (see Section A.2.9). 14 M ller was a powerful, inventive and communicative personality who espoused 'the idea' (in Goethe's sense) and made a success of it. Like Goethe, he was concerned with objects as they presented themselves to sentient experience. M ller is sometimes deemed a 'vitalist', perhaps on account of the following sentence from his Elements of Physiology 'Though there appears to be something in the phenomena of living beings which cannot be...

A32 Alternatives to Mechanism are Often Misrepresented

For mechanists, it became - and remains - easy to caricature alternative viewpoints in terms of a simple dichotomy, acceptable and unacceptable. Monod (1971) wrote 'a few words about the old quarrel between reductionists and holists . According to these holist schools, which, phoenixlike, are reborn in every generation, the analytical attitude ( reductionist ) is doomed to fail in its attempts to reduce the properties of a very complex organization to the sum of the properties of its parts. It is a very stupid and misguided quarrel, which merely testifies to the holists' total lack of understanding of scientific method ' As examples of 'holism', Monod cited a collection of papers (Koestler and Smithies 1969) written by such distinguished exponents of scientific method as C. H. Waddington and Paul Weiss. Monod's eminence is beyond question and his essay is scholarly and durable but his dismissal of alternative perspectives, in all of which he perceived 'vitalism' or 'animism',...

A33 Extreme Mechanism The 19thcentury German Materialists

Just as many vitalists in France at the turn of the century had repudiated the independence of the soul from the body, so many German materialists began to question the notion that humans had spiritual attributes. In 1846, Carl Vogt (1817-1895) wrote the following notorious words (see B chner 1864)23 'I believe that every scientist, if thinking at all consistently, will reach the opinion that all the faculties that we comprise under the name of psychic actions are nothing but functions of the cerebral substance, or, to express myself somewhat crudely, that thoughts have about the same relation to the brain as bile has to the liver or urine to the kidney'. Vogt scandalised his readers, but his sentiments were little different from those expressed by Bichat and Cabanis almost half a century earlier. Yet his biological frame of reference was wholly different he was an outright mechanist, whereas Bichat and Cabanis had been vitalists. However, if there is no vital force, how are we to...

A5 Rapprochement between the Mechanistic and Vital Materialist Approaches

What are the prospects for ending the imbalance between these two approaches more generally, and for enabling all biomedical workers now and in the future to perceive them as complementary rather than contradictory In general, vital-materialists (mainly clinical practitioners) are willing to accept the findings of mechanistic research and where possible to exploit them their difficulty is comprehension, since much of the modern biological literature looks to the outsider like a 'private language'. On the other hand, mechanists remain dismissive of the vital-materialists they tend to consider their work misdirected, antiquated, tainted with vitalism and, mistakenly, they believe that its achievements have been subsumed in their own approach.30 There is therefore a pressing need to help mechanists to achieve a clearer and better-informed awareness of the past achievements of vital-materialist research and its legacy in biology and medicine today, and to recognise its continuing...

Age Dependent Lineage Skewing of HSCs

It is well documented that a decline in immune function accompanies the natural ageing process in both mice and humans (Morrison et al. 1996, Marley et al. 1999, Liang et al. 2005). This finding has far-reaching implications given the success of stem cell transplantation using stem cells from older individuals and the etiology of age-associated hematopoietic conditions. It has been hypothesized that age-related hematological defects have their origin in cell intrinsic changes in the functional capacity of hematopoietic stem and progenitor cells (Rossi et al. 2005). Indeed, whole genome microarray analysis on purified young and old HSCs revealed almost 1,000 genes to be age-related with a high degree of statistical significance (Rossi et al. 2005). This study found that the expression of numerous genes specifying lymphoid fate and function was downregulated with age, whereas genes directing myeloid specification and function were upregulated with age. These findings are consistent with...

Photosensitivity dermatoses

Pityriasis Rubra Pilaris Face Treatment

As the aged population continues to become a higher percentage of the total population and life expectancy increases, the nutritional status of this elderly population becomes increasingly important. The vitamin deficiencies are therefore discussed as follows.

Global burden of coronary heart disease

Coronary Artery Disease Burden World

Coronary heart disease is decreasing in many developed countries, but is increasing in developing and transitional countries, partly as a result of increasing longevity, urbanization, and lifestyle changes. Civilization kills. Since 1990, more people have died from coronary heart disease than from any other cause. Unlike stroke, coronary heart disease is a comparative newcomer on the world stage. Variations in death rates are marked they are lower in populations with short life expectancy.

A41 The Metaphysical Dichotomy in Early 20thCentury Biology and Medicine

26 It was emphatically not vitalist vitalism had become extinct by the end of the 19th century. Its last significant exponent, Hans Driesch, had used 'entelechy' to explain observations in experimental embryology that seemed at the time incompatible with the dictates of physics and chemistry, but can now be 'explained' by reference to the spatio-temporal distribution of chemical groups on cell surfaces.

Bronchial Sleeve Resection

Adjacent primary tumors may produce airway obstruction by direct airway invasion or extrinsic compression (Figures 40-4A, 40-5, Figures 40-4B and 40-5C through E, see Color Plates 10, 11 ). Esophageal cancer, head and neck malignancies, and thyroid cancer may all result in tracheal obstruction that can be palliated by stent placement. Esophageal cancer may also result in a malignant tracheoesophageal fistula. These patients commonly have a short life expectancy, but the contamination of the airway by salivary and gastric contents may be minimized by a covered esophageal stent or covered tracheal stent, or both. Expandable endoesophageal stents have produced a marked improvement in the palliation of patients with malignant esophageal obstruction. However, when these stents are placed in the upper esophagus, they may result in a secondary extrinsic compression of the trachea or mainstem bronchi. If the esophageal stent cannot be removed, then the airway can be palliated with a second...

Atomism Descartes and Gassendi

Other historians have written books on the influence of vitalist and mechanistic thought, particularly that of the alchemists Paracelsus and van Helmont and their followers and the Cartesians and Gassendi on English natural philosophy. This section is not synoptic instead, I focus on aspects of Continental thought on bodily spirit and matter that were problematic for English Harveians at mid century. The vitalism of Paracelsus and van Helmont as well as the mechanism of the Cartesians loomed large in that respect. Within the Oxford and London experimental clubs, reception of their ideas was partial and contingent. In comparison, English investigators quickly and more or less completely incorporated work by Continental anatomists that confirmed and expanded Harveian models. For example, Jean Pecquet's discovery of the thoracic duct, disclosed in 1651, stimulated considerable work at Oxford on chyle and the role of the liver in blood production within three years of its publication....

Autosomal Dominant Cerebellar Ataxia

Clinical Features and Associated Disorders. Cerebellar aplasia seldom occurs alone. It is characterized by complete or near complete absence of the cerebellum. The clinical picture of patients with cerebellar aplasia is variable. The life expectancy of patients with this disorder ranges from a few weeks to a normal life span. In general, patients with cerebellar agenesis have profoundly impaired motor development and persistent motor deficits. However, there are reports of patients with subtotal cerebellar aplasia who learned to stand, walk, and run. Compensation appears to be best if intelligence is normal. y

Complications of penile prosthetic surgery and their management

Erectile Radiology

If mechanical problems in an inflatable device develop after surgery, a trend to remove and replace the entire device has emerged recently. Common mechanical failures are tubing fracture, cylinder or reservoir leak, cylinder aneurysm, or connector disruption. Most urologists consider that replacing the entire device will give the patient added longevity in all parts 14,30 . Certainly after two or three years, it is prudent to replace all the prosthesis components because there can be significant wear of the device within that period. In addition, repeated penile incisions to change cylinders may shorten the penile length 34 . Furthermore, bacteria-positive cultures of clinically uninfected penile prostheses have been found in 70 of tested implants. In some patients, more than one organism grew, and in some patients the pump culture was negative but the biofilm was positive 35 . This may explain the higher infection rate that occurs with revision surgery 36,37,38 . Combining complete...

Rationales And Mycological Backgrounds

Although fungi may produce abundant spores, many fungi may have only a portion of spores viable and thus capable of germination and growth. Stachybotrys chartarum reportedly has only a small percentages of the conidia available in laboratory cultures. 18 In addition, growth of the fungus is inhibited by different species of Penicillium.18 The second edition of the Field Guide for the Determination of Biological Contaminants in Environmental Samples2 provides a table of longevity of spores of 18 fungi under air-dry conditions. Spores of S. chartarum are reported to have a half-life of approximately 0.8 year. This implies that the spores will die out in about 5 years if there is no moisture for germination, growth, and reproduction. Spores may lose viability over time if no suitable germination and growth conditions are available. Some fungal spores are known to remain viable for years.2,7,19 A wide range of viability of fungi in laboratory storage, with several different storage...

Mitochondrial DNA Mutations and Aging

Mitochondrial DNA alterations in aging postmitotic cells have been examined extensively. Aging is associated with both mtDNA deletions and mtDNA point mutations. The highest levels of age-associated multiple mtDNA deletions are observed in postmitotic tissues with high energy demands such as heart, skeletal muscle, and brain 70,71 . The search for mtDNA point mutations in tissue homogenates of aging individuals gave rather disappointing results with very low levels of specific mutations (0.04 -2.2 ) 72 .When single cells were analyzed, mtDNA point mutations were observed to accumulate to high levels in an age-dependent and tissue-specific manner 73,74 . Several of them accumulated up to 50 in single skin fibroblasts of individuals over 65 years of age 74 . Still, there was an open question if mtDNA mutations could be a driving force of aging or are just secondary to the aging process. Recently, we have developed a mouse model that provided the first experimental evidence for a...

Predisposing factors to developing cancer

As society becomes more affluent, so the incidence of cancer can be demonstrated to rise. There could be a number of explanations for this, including increased wealth and improved health care enabling individuals to achieve a greater life expectancy than their grandparents (Gabriel, 2001). People are also surviving previously life-threatening illnesses, such as infectious diseases, major accidents, etc., only to live longer and possibly to develop cancer later in life. We also know that more affluent societies consume higher amounts of convenience foods, alcohol and tobacco, as well as being exposed to higher levels of chemicals and pollutants compared with people living in some less developed parts of the world. All these factors can contribute to an individual developing a malignancy (Venitt, 1978 Cartmel and Reid, 2000 Corner, 2001). Other factors can include past exposure to ionizing radiation, viruses and a genetic disposition (Cartmel and Reid, 2000 Yarbro, 2000a).

Important Findings In The Pediatric Emg Laboratory

The onset of SMA type II is typically from 6 to 18 mo, with some cases beginning as early as the neonatal period. These children often present with motor delays. They eventually sit independently but never walk, and survive only to adolescence or early adulthood. The gait difficulties that are often the first signs of SMA type III usually begin after 18 mo. These patients walk independently for most of their lives. Life expectancy is normal in most cases of SMA type III, although some patients require wheelchair assistance as adults.

Heterogeneity The Hallmark of Ageing

Ageing is characterized by random accumulation of unrepaired cellular and molecular damage. The mechanisms involved are inherently stochastic, i.e., driven by chance (Kirkwood 2005). In fact, several studies have demonstrated stochastic heterogeneity as an important feature of the ageing process Examining the effect of ageing on cell integrity in different tissues of Caenorhabditis elegans by electron microscopy (Herndon et al. 2002), it was found that stochastic factors are clearly involved in the ageing process and that different cell types deteriorate at different rates. Apart from heterogeneity on a tissue and cellular level, the wide interindividual variation in life span of C.elegans nematodes, even in isogenic populations under very homogeneous environmental conditions, indicates the intrinsic randomness of the ageing process (Kirkwood and Finch 2002). This heterogeneity in life span variation of isogenic C. elegans populations has been attributed to chance variation in...

Adulthood And Aging Social Processes And Development

Close social partners provide emotionally meaningful interactions, and satisfaction with family members, including siblings, spouse, and children, increases with age. The sibling relationship represents one of the longest, more enduring relationships in life, and Victor Cicirelli's (1989) research reveals that people who report positive relationships with siblings, particularly their sisters, also report lower levels of depression. In addition, the marital tie is also important to overall well-being. Across the life span, marital satisfaction follows a curvilinear pattern high in the early years of marriage, decreasing slightly into middle adulthood, and then rising again toward the end of middle age. People whose marriages survived into old age report high levels of marital happiness and contentment. Although they reported that difficult times did occur, they attribute their marriage's longevity to strong levels of mutual commitment and friendship. The majority of research has...

Controlling Vascular Endothelial Growth Factor Therapies For Ocular Diseases Associated With Neovascularization

A primary drawback in the use of oligonucleotides as a therapeutic has been the relative biological instability of the compound. Oligonucleotides are generally short lived in vivo, and while the use of modified chemistries has led to improved half lives, longevity remains a limiting issue and re-administration is required on a regular basis. In this respect, gene therapy, whereby a modified, recombinant gene is inserted into the genome, is a superior method of controlling gene function. Once inserted, the new gene remains functional for an indefinite period, producing the therapeutic agent for the life of the cell. In addition to longevity, specific cell types may be targeted for gene expression through the use of cell and tissue specific promoters, which control gene expression. This approach may be useful for systemic delivery of gene constructs as it ensures that the gene is not expressed in tissues where its presence may prove detrimental. For the control of VEGF associated with...

Heart Related Diseases

There has also been an increase in average life expectancy. People now live long enough to succumb to diseases that develop slowly, such as many cardiac diseases, particularly coronary heart disease. Lifestyles, too, have changed. Lack of physical activity and changes in diet may contribute to increased coronary heart disease.

Viability of Fungal Spores

Fungal spores can remain viable for a short period, for weeks or as long as many years, depending on the fungal species, spore types, and storage conditions.1 It appears that under the same conditions, chlamydospores and resting spores survive longer than do other types of spores ascospores, longer than basidiospores and smaller-sized conidia (e.g., of Aspergillus or Penicillium), longer than dark-colored, larger spores (e.g., Stachybotrys, Ulocladium), although this kind of generalization is often challenged. Most spore longevity data are derived from experimental records, and those laboratory conditions may not reflect field conditions. These data should be used only as an estimation of spore longevity. Indoor fungi are mostly in an open environment that has many factors affecting the survi-vability of fungi, such as desiccation, temperature, chemicals, and radiation. The common belief is that the number of viable fungal spores reported as CFUs

Physiology of Salivary Glands

Abdominopelvic Cavity

About 1 l of saliva is secreted by a normal adult each day. During unstimulated salivation, 69 of saliva is contributed by the submandibular glands, 26 by the parotid, and 5 by the sublingual glands. The relative amounts supplied by the parotid and submandibular glands, however, are switched during stimulation, where two thirds of secretion is then from the parotid gland. Of total flow, 7-8 is due to the minor salivary glands regardless of stimulation. The presence of food in the mouth, the act of chewing, and nausea all stimulate salivation, while sleep, fatigue, dehydration, and fear inhibit it. Salivary secretion rates are not dependent on age, and flow rates remain constant despite the degeneration of acinar cells during the aging process. Medication side effects or systemic disease are more likely to be responsible for hypofunction of salivary glands in elderly patients 15, 17 .

Stem Cells of the Liver and

If we believe that tumours have their origins in normal stem cells, or at least in cells with sufficient longevity to acquire multiple genetic mutations, then we need to appreciate normal cell turnover in the liver and intestine. Foetal liver is a source of bipotential progenitor cells (hepatoblasts) as seen by their extensive colonisation of the diseased livers of rats after transplantation.8 In postnatal animals, hepatocytes are highly differentiated cells with multiple synthetic and metabolic functions they are also the functional stem cells in the liver under most circumstances. In health, individual hepatocytes have a life expectancy of over a year. Therefore in the normal adult liver, there is little cell proliferation detectable with only 0.01 of hepatocytes in the cell cycle at any one time. However, in response to parenchymal cell loss, hepatocytes restore the liver mass by self-replication. This is a very efficient system and in rodents, when two-thirds of the liver is...

Nonhereditary Idiopathic Cerebellar Ataxia

While IDCA-C patients have an almost normal life expectancy, the prognosis for those with IDCA-P MSA is poor. Patients become wheelchair-bound approximately 5 years after the onset of disease. Median survival after disease onset is 8 to 10 years. y , y The cause of IDCA is unknown. Unlike the situation with the hereditary ataxias, major progress in understanding the pathogenesis of IDCA is not to be expected in the near future.

Chronic Angst Allostasis and Pathology

Provide physiological and behavioral resources that help maintain equilibrium. Unfortunately, these resources are finite. Chronic signals from physiological mediators (cytokines, cortisol, catecholamines, etc.) take their toll on bodily function, resulting in vulnerability to a variety of diseases such as those that concerned Sterling and Eyer (1988) and later McEwen and Seeman (1999 including hypertension, diabetes, atherosclerosis, bone loss, sleep disruption, disruption of immune and reproductive functions, inhibition of neurogenesis, aging process Seeman et al., 2001). Vulnerability to these events can occur from prenatal events (Barker, 1997 Welberg and Seckl, 2001).

Factors And Signals Promoting Cardiogenesis In Vertebrates

F EBs lacking of both diffusible and matrix-bound forms of LIF (lif-1) EBs) showed a severe suppression of early differentiation of cardiomyocytes (Bader et al., 2000). Furthermore, onset of differentiation could be rescued by a very low concentration of D-LIF, but consecutive differentiation was attenuated in a concentration-dependent manner by increasing D-LIF concentration in wild-type and lif-7- cardiomyocytes. At fully differentiated state, paracrine and autocrine LIF promoted proliferation and longevity of cardiomyocytes. Bader et al. (2000) suggested that both D-LIF and M-LIF contribute to the modulation of cardiogenesis in a subtile, opposite manner and control proliferation and maintenance of the differentiated state of cardiomyocytes.

Where Do the Cancers Arise

The assessment of DNA alterations in tumour cells allows a precise determination of their clonality. Where HBV is involved, there is no doubt that the integration of HBV-DNA into the hepatic genome is a significant event in hepatocarcinogenesis.1,35,36 Moreover inspection of viral integration sites amongst tumour cells clearly indicates that each tumour is monoclonal, i.e. derived from a single cell.37-40 Likewise, studies of HCC clonality based on restriction fragment length polymorphisms of X-linked genes such as the androgen receptor gene (HUMARA) come to the same conclusion.41 The important question is, which cell is involved in cancer initiation As discussed above, in the liver there are many cells endowed with longevity and long-term repopulating potential, suggesting that there may be more than one type of carcinogen target cell. Irrespective of which target cell is involved, what is clear is that cell proliferation at the time of carcinogen exposure is pivotal for fixation of...

Malignant Tracheoesophageal Fistula

Figure 26-6 Palliative treatment of malignant tracheoesophageal fistula by exclusion and esophageal bypass. The text notes variations of this procedure. It may be justifiable in a few patients, whose prospects for longevity are unusually encouraging. A, Collar incision with upper sternotomy provides access to the upper esophagus to a point just above the tumor, and later for esophagogastric anastomosis. Laparotomy allows omental mobilization, gastric mobilization, pyloromyotomy, and intrathoracic excision of the lower esophagus up to the tumor (with additional anterior diaphragmatic incision). B, Diagram of components of procedure. Esophageal division above and below the tumor and fistula converts this to a diverticulum of the trachea. The lower esophagus is removed. The stomach is fully mobilized with omentum remaining attached, and both are nourished by the right gastroepiploic artery. Pyloromy-otomy or pyloroplasty is necessary. The stomach is advanced through a substernal tunnel...

Role of Telomere Length and Telomerase in Human Disease

In addition, several human premature ageing syndromes are characterized by a faster rate of telomere attrition with age, such as Dyskeratosis congenita (DC see Du et al., this volume). DC patients carry mutations in components of the telomerase complex which result in decreased telomerase stability and shorter telomeres (Mitchell et al. 1999). These mutations affect either the Terc gene (patients with the autosomal-dominant DC variant) (Vulliamy et al. 2001, Vulliamy et al. 2004) or the dyskeratosis congenita 1 gene (DKC1) (patients with the X-linked form of the disease), which encodes a protein involved in Terc stability and snoRNA processing (Mitchell et al. 1999). Both mutations result in decreased telomerase activity and shorter telomeres compared to healthy individuals (Mitchell et al. 1999, Vulliamy et al. 2001, Vulliamy et al. 2004). In addition to DC and aplastic anemia patients, who have defective telomerase activity and short telomeres, a number of additional human premature...

Telomerase For The Development Of In Vitro Models Of Cancer Progression

The ability of telomerase to immortalize cells without altering the underlying genetic background has also been demonstrated in cells with inherited susceptibility syndromes, such as ataxia-telangiectasia, Bloom syndrome, xeroderma pigmentosum and premature ageing syndromes such as Werner syndrome and Hutchinson-Gilford pro-geria. Thus, telomerase may be an important tool for establishing premalignant cell lines which can be used for the development of in vitro models of cancer progression, for amassing large numbers of cells required for other assays or as standard cellular reagents for microarray analysis. Microarray is a novel technique which utilizes microchip technology to analyze cellular RNA for changes in patterns of genetic expression in mutated cells versus their normal counterparts.

The sexual division of labor

Stringent sexual division of labor was resurrected, however, by the relatively cumbersome technology of steam powered machines introduced at the early stages of the industrial revolution, only to diminish again with the introduction of electric power and the advances in medicine. Electric power (and more recently hi-tech electronics) brought industry closer to home and enabled more flexible work schedules. Advances in medicine, especially in preventive medicine, prolonged considerably life expectancy. Taken together, these two developments helped to extend the effective working life span of women well into, and long past, child-bearing age so much so, that the nonagricultural labor force participation rate of married women (an inverse measure of the sexual division of labor) went up in most developed countries from about 5 early in the twentieth century to nearly 60 toward its end. All in all, sexual patterns of division of labor in human societies seem to be highly adaptable in...

Telomere Shortening and Organismal Aging

Of this hypothesis, increasing evidence links human premature aging syndromes and mouse models of premature aging with DNA damage-induced genome dysfunction. Mutant mice unable to repair accumulated DNA damages exhibit symptoms of premature aging and die early (Rudolph et al. 1999, Tyner et al. 2002, Cao et al. 2003, de Boer et al. 2002, Wong et al. 2003), suggesting that proper maintenance of genomic integrity is essential for longevity. Late-generation telomerase null animals display a subset of aging phenotypes, including alopecia, hair greying, a reduced stress response, and decreased longevity (Rudolph et al. 1999). These animals also exhibit elevated genomic instability, manifested as chromosomal fusions and increased cancer incidence. Enhanced sensitivity to genotoxic agents such as ionizing radiation and alkylating agents is also noted in late generation mTerc ' mice and derivative cell lines (Wong et al. 2000, Goytisolo et al. 2000, Lee et al. 2001), suggesting that...

Cytotoxic Effects of Chemotherapy

The effects of chemotherapy on ovarian function are both agent and dose-dependent, and this effect may be additive to that resulting from abdominopelvic radiotherapy. Alkylating agents affect the resting oocyte in a dose-dependent, cell cycle-independent manner. Thecal cells and ova are depleted, as are the primordial follicles, resulting in arrest of follicular maturation and decreased estrogen secretion. Again, as was the case with radiotherapy, the effects are more pronounced in post-pubertal as compared with prepubertal females, due to the fact that post-puber-tal females have fewer remaining viable oocytes. The effects worsen with age, as the normal aging process is accompanied by an ongoing depletion of oocytes. Risks of menstrual irregularity, ovarian failure and infertility increase with age at treatments. Conversely, younger females can tolerate higher doses of alky-lating agents without impairment of fertility, compared with adult females 10-15 .

The US Carvedilol Program

The proponents of carvedilol assembled a collection of compelling arguments both during and after the disputatious FDA debate. There was no question about the strength of the US Carvedilol's programs findings. Lives were prolonged for patients who had a disease that had no known definitive therapy and whose prevalence was rapidly rising. The Data Safety and Monitoring Committee* of the program had stated that, in the face of the large mortality benefit, it was unethical for the trial to continue merely to demonstrate an effect on its weaker endpoints. The FDA was reminded that the most compelling of all endpoints in clinical trials is total mortality, and the most laudable goal was prolonging life. There was no doubt that carvedilol had produced this precise result in the US Carvedilol Program.

Binary Oppositions in 17th18thCentury Medicine

General accounts of history often portray the past in terms of opposed pairs of metaphysical viewpoints5 Galenist versus Harveyan, humoralist versus solidist, vitalist versus mechanist, and so on. We shall follow this practice because it cannot 5 The once-fashionable structuralist Claude L vi-Strauss held that the representation of experience as a set of binary oppositions - nature culture, male female, light dark, etc. - is fundamental to the structure of the human mind, universal among preliterate societies and commonplace in developed cultures. Whatever the credibility of this judgment, it is difficult altogether to avoid the reduction of knowledge to such pairs of opposites, especially in outline accounts of the history of ideas. However, it is potentially misleading and can lend itself to the most vulgar rhetoric. An extreme 'mechanist' declaring 'either you share my beliefs wholly or you're a vitalist' seeks to marginalise anyone who draws attention to the philosophical pitfalls...

Primary Prevention Of Psychopathology

Most of the enormous improvement in the health and increasing longevity of members of our society has come about as a result of the successful application of the methods of primary prevention within the field of public health. Public health prevention methods involve finding the noxious agent and taking steps to eliminate or neutralize it, or strengthening the host.

The Coping Strategies Of Hiv Htlvi And Htlvii

The strategy of both HTLV viruses in the absence of intravenous drug usage and rapid movements of peoples was very close to the gentle pathogen persuasion. Both viruses persist with little damage to their host by replicating very slowly while being passed vertically or between adults as an STD. Being poorly transmitted from cell to cell and individual to individual favors the gentle character, but another feature is that they have mechanisms to cause the T-cells to replicate. In AIDS, depletion of T-cells in long-term HIV infection occurs, but this does not occur in HTLV. This allows more opportunities for the virus to be transmitted between humans. These viruses are poorly transmissible and transmission from male to female is rare and the transmission from female to male is very slow (at least for HTLV-I). Though it is passed presumably in the same three ways that HIV is passed to the neonate i.e., in utero, perinatally by blood-to-blood transfer, and (predominately) postnatally via...

Cellular versus Organismal Aging

Abstract Aging is an extremely complex process, affecting individual cells and organisms as a whole. Here we discuss the impact of telomeres, the natural chromosome ends, on cellular and organismal aging, and how telomere maintenance influences genome stability and tumorigenesis. Since telomeres represent only a fraction of the complexity of the aging process, we discuss how genome integrity and DNA damage response pathways affect postmitotic aging, and which genetic pathways promote survival and elongated life, namely the IGF-1 signaling pathway, dietary restriction, and mitochondrial transport chain. At this point the researchers in the field are intensely studying individual aspects of aging, but it remains a unique challenge to integrate all aspects, with the goal of understanding longevity.

Preoperative Evaluation

A thoughtful assessment of comorbidities, including cardiovascular and pulmonary risk factors is critical in allowing for the appropriate choice of procedures and adjunctive modalities. For example, a patient with advanced COPD may do better with an expeditious procedure performed under regional rather than general anesthesia. Alternatively, a patient with significant coronary artery disease and a short life expectancy may be more appropriately selected for local excision of a rectal cancer rather than radical resection.

Genetic Pathways of Postmitotic Cell and Organismal Survival

Fig. 1.2 Reduced insulin IGF-1 signaling (IIS) synergizes with perturbations in other longevity pathways. Representative life span analysis of worms with combinatorial inactivation of IIS, diet restriction, or reduced mitochondrial electron transport chain (ETC) activity is depicted. A) Combination of diet restriction (depicted as red line) with reduced IIS (green line) results in animals that live longer than either single perturbation (blue line). B) Combination of reduced ETC (depicted as yellow line) with reduced IIS (green line) results in animals that live longer than either single perturbation (cayenne line). For more details of separation of these three pathways, please see text (See Color Plate) Fig. 1.2 Reduced insulin IGF-1 signaling (IIS) synergizes with perturbations in other longevity pathways. Representative life span analysis of worms with combinatorial inactivation of IIS, diet restriction, or reduced mitochondrial electron transport chain (ETC) activity is depicted....

The other end of life Why do we age and die

Interestingly, medical advances have increased the average life expectancy, but this has been accomplished solely by preventing death during younger years. Nothing in medical science has extended significantly the maximum age of about a century that individuals can reach we simply increase the number of individuals who live to approach that maximum.

Winnipeg Jets Standings

Form of p53 display premature ageing phenotypes such as reduced longevity, osteoporosis, generalized organ atrophy, and diminished stress tolerance (Tyner et al. 2002). Moreover, it has been shown that hypermorphic levels of p53 in these mice affect hematopoietic stem cell (HSC) number, proliferation, and _ functionality with age, whereas deletion of one copy of p53 increased HSC proliferation during mouse ageing (Dumble et al. 2007). In contrast, telomere dysfunctional mice carrying an extra copy of wild-type p53 gene under its natural promoter (total three copies of p53) did not show an increase in tissue atrophy or a shortening in life span (Garcia-Cao et al. 2006). These results were surprising since telomere dysfunctional mice carrying an extra copy of p53 are expected to have a 1.5-fold increase in p53 gene dosage when compared to telomere dysfunctional mice with only two copies of p53. Notably, the in vivo load of telomere-derived chromosomal damage was significantly decreased...

Harvey and the Physiological Approach

We can generalise this assessment not everyone who declined to adopt a radical 'mechanist' stance (in the Cartesian sense of 'mechanist') in the 17th and 18 th centuries can be automatically labelled a 'vitalist'. The point is moot in Harvey's case. Exposed to the newly evolving metaphysic of natural philosophy from his formative years and a strong proponent of the Baconian approach to experiment, Harvey refuted Galen's account of blood movement and laid the foundations of modern physiology (see Chapter 8) but he was not a 'proto-mechanist' like the iatrophysicists and iatrochemists. Yet to deem him a 'vitalist' would not merely be anachronistic, it would be absurd it is hard to find a 17th-century writer less inclined towards mystical notions than Harvey. In refuting Galen, he distanced himself from mediaeval tradition no less sharply than those of his contemporaries whom we might term 'proto-mechanist'.

Late 18th and Early 19thcentury Studies of Blood Chemistry

The benefit of the new chemical approach to what was to become 'haematology' is beyond question. The cost was the eventual divorce of this mechanistic program from work being undertaken in parallel from the 'pathophysiological' standpoint. Perhaps paradoxically, many of these early animal chemists did not accept the mechanistic metaphysic, at least not wholly several of them were vitalists or included vitalistic elements in their writings. Some of the publications by Stevens (see above), and even Liebig, suggest vitalism. This makes it particularly misleading to equate proponents of the pathophysiological approach with 'vitalism' and proponents of the mechanistic approach with 'mechanism'. The historical reality is more diverse.

HSC Gene Expression Profiles Transcription Factors and Epigenetic Modification

Recently, epigenetic modifiers of gene expression have emerged as important regulators of stem cells and the ageing process. In addition to direct sequence-specific genetic variations, epigenetic changes to chromatin structure and covalent modification of histones play important roles in regulating gene transcription throughout the life span of an organism. Expression of genes mediating epigenetic processes changes with age (Rossi et al. 2005), suggesting that epigenetic modifications may contribute to HSC ageing. In HSCs a particular class of epigenetic modifiers termed the polycomb group (PcG) proteins are important regulators of self-renewal and cell fate determination. PcG proteins are transcriptional repressors that silence expression of transcripts promoting differentiation in human and mouse embryonic cells (Boyer et al. 2006, Kamminga et al. 2006). One PcG protein in particular, Bmi-1, is required for efficient self-renewing divisions of adult HSCs (Lessard et al. 1998, Park...


Of the 30 million cases in 1997, almost 21 million were in sub-Saharan Africa alone (where in some places, such as Botswana, upwards of 36 percent of the adult population has become infected with HIV), while South and Southeast Asia and the Pacific accounted for another 6 million cases. In all, the developing world contained 95 percent of the cases, and in 1998 it was estimated that 70 percent of all new infections and 80 percent of all AIDS deaths occurred in sub-Saharan Africa. By 2001, average life expectancy south of the Sahara had declined by 10 years and infant death rates had doubled. Illustrative of the impact of AIDS mortality is the example of Zambia, where a dire shortage


Stands in terms of therapy development. Nicol Keith and Alan E. Bilsland focus on anticancer therapies targeting telomerase or telomere structure. Given that human cancers have very short telomeres and high levels of telomerase compared to non-transformed human tissues, destabilization of telomeres and inhibition of telomerase could both be promising targets in anticancer therapy. It is exciting to see that the first cancer clinical trials have been initiated using a novel telomerase enzyme inhibitor. Somewhat unexpected have been early successes using a telomerase immunotherapy for cancer therapy. In the final chapter Terence Davis and David Kipling introduce therapeutic approaches targeting stress signals downstream of DNA damage and or telomere dysfunction in Werner syndrome patients these approaches aim to improve cellular and organismal fitness during ageing. Although they focus on Werner syndrome, it is likely that some of these connections also apply to normal ageing...


Cellular and organismal aging is influenced by multiple parameters, such as telomere length, telomere shortening rates, the DNA damage response machinery, dietary restriction, mitochondrial metabolism, and the insulin-signaling pathway. Currently it is not well understood how these pathways interact, how the determinants of organismal life span influence cellular aging, and how or if the cellular clock limits organismal longevity. It remains a unique challenge to the aging research community to integrate the various aspects of the field, to realize the connections to age-related diseases, and to exploit these realizations for healthy aging.

Classic Hemophilia

Classic hemophilia varies in severity from family to family. In the most severe cases, in which plasma is essentially devoid of factor VIII, the patients may bruise readily and bleed apparently spontaneously into soft tissues and joints, with the latter resulting in crippling joint disease. Trauma, surgical procedures, and dental extractions may lead to lethal bleeding. The life expectancy of those with severe classic hemophilia is foreshortened, death coming from exsanguination, bleeding into a vital area, or infection. The prognosis of classic hemophilia has been greatly improved by modern therapy in which episodes of bleeding are controlled by transfusion of fractions of normal plasma containing the functionally missing proteins. This therapy is not without hazard, for transfusion of concentrates of factor VIII derived from normal plasma has been complicated by transmission of the viruses of hepatitis and the acquired immune deficiency syndrome (AIDS).


Cancer is predominantly an illness of middle age and, with a few exceptions, is relatively rare in children. Thus, people in the developed world, having escaped famine and epidemic disease, have extended their life expectancy into the ages in which cancer frequency is increasingly high.

Shift work

This has been shown in several studies, but the cause is uncertain. It may be related to repetitive cycles of internal desynchroniza-tion of circadian rhythms, but other factors including increased alcohol consumption, and tobacco smoking may be relevant.


Increasing life expectancy has led to remarkable growth in the older adult population. According to the 2000 U.S. Census, 35 million older Americans, or 12.4 of the U.S. population, is over the age of 65. The over-85 age group includes 4.2 million Americans, the fastest growing age group in the United States. With the aging of the baby boom cohort, there will be 70.3 million Americans over age 65 in the year 2030. The rapidly growing older population and the significant impact of aging on physical, psychological, and social functioning suggest that knowledge about gerontology (normal aging) and geriatrics (clinical aging) will become vital for researchers, clinicians, and policy makers.

Future Issues

Census data suggest that 25.4 of the elderly population in 2030 will be members of racial and ethnic minority groups. Increasing life expectancy among racial and ethnic minority groups means an increasingly diverse aging population and thus, interventions for older adults should be developed and provided in culturally sensitive and appropriate ways. Clinicians should consider factors such as cohort-specific discrimination and different values concerning caregiving and mental health issues held among different ethnic minority elderly groups.

Diabetes mellitus

Treated by lifelong daily insulin injections, although if inappropriately managed, this carries an increased risk of hypoglycaemia, and the restoration of normoglycaemia does not always alleviate the aforementioned secondary complications, and patients often have a reduced life expectancy.4

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