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Vascular Genetic Factors and Human Longevity

Complex interrelationships between age-associated illnesses such as vascular disease and AD indicate that biological and genetic pathways may be worthy of examination in centenarian populations to provide insights into human longevity. This is also borne out by the involvement of lipoprotein metabolism and a number of vascular genetic risk factors 20, 21 . The search for factors involved in aging and longevity has progressed extensively in recent years because of increased human life expectancy and elevation of the number of elderly people, which in turn results in increased prevalence of age-related illnesses. Different genetic and nongenetic factors have been examined in the quest to understand the biological basis of human longevity. For example, centenarians are characterized by marked delay or escape from age-related diseases, such as coronary artery disease (CAD), cerebrovascular disease (CVD), and AD, which respectively are the first, the third, and the fourth largest causes of...

Inflammation and Immune Response in Human Longevity

Aging is not synonymous with illness. However, aging does increase the risk for certain illnesses. Overall, elderly people have an increased rate of chronic disorders, infections, autoimmune disorders, and cancer. A significant part of this increased risk seems to be related to aging changes in the immune system. With age, the number of immune cells may decrease slightly. More important, the functioning of these cells declines. The cells are often less able to control illness than in earlier years. As a person ages, the immune system produces fewer antibodies. It also responds more slowly to injury, infection, or disease. Cells of the immune system can also lose their ability to tell the difference between normal and abnormal tissue. Accordingly, several studies have shown an association between in vitro T cell function and longevity, suggesting that a well-preserved immune system may be associated with extended longevity 83 . Therefore, centenarians are the best examples of...

Limits On Life Expectancy And Future Prospects

Because we do not understand the mechanisms of biological aging or the reasons for aging, estimating the limits of human life expectancy is highly empirical. There is a strong evolutionary and genetic influence on life expectancy (7-9). The forces of natural selection decrease with advancing age because, in natural populations, few individuals survive past the reproductive ages. Therefore, among the survivors, random mutations (alleles) will accumulate and their detrimental effects will be expressed after reproductive activity has ceased. In recognition of those ideas, Williams (10) proposed an antagonistic pleiotropy hypothesis, which suggests that disadvantageous genes in a population will not be selected against if they arise after the reproductive phase that is required to maintain the population. A related theory is that of the disposable soma theory (11), the concepts of which were summarized by Holliday (12) as follows Finch (9) has reviewed the relationships between life-span...

Introduction Bad Medicine Better Medicine

I am tall, over six feet. The vast majority of people over six feet tall have been born in the last century, perhaps in the last thirty years. In the mid-eighteenth century Frederick the Great of Prussia searched across Europe to assemble a regiment of men over six foot tall the enterprise took its point from the rarity of such giants. Anybody inspecting my body for a post mortem would find that on my upper arm there is the scar of a vaccination against smallpox, which must have occurred after 1796, when Jenner invented vaccination, and before 1980, when smallpox was officially declared eradicated. They would also find evidence of my surviving an appendix operation and a compound fracture of the tibia this, as we shall see, implies medical care received after 1865. Before that date an appendectomy was almost certain to be fatal, while the only hope for someone with a compound fracture (where the bone sticks through the skin) was amputation. The...

Nucleic Acids Genes and Gene Products

The end regions of chromosomes are composed of the nucleotide sequence TTAGGG repeated hundreds of times and are called 8elomeres . Telomere sequences are lost each time that a cell replicates until the cell loses its ability to divide as part of the aging process. Telomerase is a specialized DNA polymerase that replaces the DNA sequences at the telomeres of the chromosomes. Telom-erase allows cells to divide indefinitely, a factor that can be important in cancer.100-115

Azidothymidine See AZT

AZT (azidothymidine) A synthetic pyrimi-dine dideoxynucleoside analog that inhibits replication of retroviruses, including HIV by interfering with DNA synthesis mediated by the viral reverse transcriptase. AZT-5'-triphosphate interacts preferentially with reverse transcriptase rather than cell DNA poly-merase. The use of this drug by oral administration in vivo is recommended for reducing viral load, restoring T cell function, and prolonging life in persons with clinical AIDS. It is also recommended for use in HIV-infected pregnant women in order to reduce the risk of transmission of HIV to the baby. The drug is toxic to dividing cells such as bone marrow cells, and drug-resistant HIV mutants arise readily the benefits of AZT therapy need to be balanced against these opposing factors. Synonyms 3'-azido-2',3'-dideoxythymi-dine AZT azidothymidine retrovir zidovudine.

The Role of Damage Response Pathways in Stem Cell Aging

Cell numbers at the risk of increased tumorigenesis. For example, p21, encoded by Cdknla, a cell cycle inhibitor and downstream target of p53, is upregulated in response to short telomeres, consistent with it being important in averting catastrophic genomic rearrangements via processes that eliminate cells (74, 77). In the context of telomeres and aging, a recent study examined the combined effects of Terc and Cdkn1a deletion. The absence of p21 in fourth generation (G4) Terc ' mice, with critically short telom-eres, prolonged their lifespan and improved stem cell function in the hematopoietic system and intestinal epithelium (78). Surprisingly, it did so without an acceleration of tumorigenesis. The fact that p21 deletion did not extend lifespan to that found in G4 Terc-+ mice, demonstrates that both p21-dependent and p21-independent mechanisms limit longevity in the context of telomere dysfunction (78).

And Aging or Anemia of Aging

Currently, individuals aged 65 and older represent 12 of the US population and by the year 2030 they are expected to represent 20 (1). The segment of the population increasing more rapidly than any other involves individuals over 85, the so called oldest old. The mean life expectancy of the population was around 60 years in 1900, is currently 80 for women and 76 for man and is expected to rise to 84 and 80, respectively, in 2030 (1).

Physiological Functions of Autophagy

Abstract The field of autophagy research has advanced rapidly in recent years, with important discoveries made in relation to both molecular mechanisms and physiological functions. Initially, autophagy was thought to be primarily a response to starvation. Although this might be true in lower eukaryotes, this catabolic process exerts various physiological functions in higher eukaryotes. This review summarizes the physiological roles of autophagy in amino acid pool maintenance, intracellular quality control, development, cell death, tumor suppression and anti-aging.

Recent Advances In Studies On Glycosides Of Araliaceous Plants

Ginseng, the most famous oriental drug in the world has long been used as a tonic or a drug of longevity in Chinese traditional medicine. A number of triterpenoid glycosides derived from protopanaxatriol, protopanaxadiol and oleanolic acid have been isolated and identified. Two new glycosides named ginsenoside-F5 (1) and ginsenoside Rd2 were isolated from the leaves with the aim of searching for dammarane saponin with biological activity of reducing the toxicity induced by some anticancer drugs l,65 , Ginsenoside F5 is the first example of protopanaxatriol-type saponin with arabinofuranose from the taxon within P. ginseng species. The study indicates that arabinopyranoside and arabinofuranoside coexist not only in protopanaxadiol-type but also in protopanaxatriol-type in the same plant. In the course of search for new natural sources of biologically active saponin of reducing side-effects induced by prednisone, another new dammarane saponin, ginsenoside-I, (2), was isolated from the...

Estimating Soil Microbial Activity

Whenever energy-rich compounds are added to soil, changes in constitutive and or induced microbial enzyme activity can be detected within just a few minutes to a few hours, as long as nothing else is limiting and enzyme activities are at sufficient levels to be detected. However, the induction of enzymes from previously unexpressed metabolic pathways (nonconstitutive enzymes) is generally much more easily recognized than changes in constitutive enzymes, which are also likely to be present in other soil organisms (e.g., roots, fauna). After depletion of energy-rich compounds, such as phenolic acids, the induced enzyme activity should return to preinduction levels as quickly as it was induced. The longevity of any enzyme activity in the soil will be determined by rates of enzyme synthesis and degradation. Thus, such changes in constitutive and induced enzymes are largely ephemeral unless inputs of energy-rich compounds at nontoxic levels are continued for extended periods and end...

Implications and Policy Recommendations

To aid the design of successful ART programs in resource-poor settings, more information on the impact of ART provision is crucial, including data on tolerability, treatment failure, and emergence of drug-resistant strains. Such data would help in the design of cost-effective programs that would maximize benefits to patients and increase the longevity of drug effectiveness. The most suitable drug regimens for the target population must be procured at the lowest possible cost (in generic versions where possible). Factors to consider include drug potency, efficacy in inhibiting viral replication, convenience, tolerability, and the implications of failure for future treatment options. Drugs with greater potency, which are metabolized slowly and which require many mutations in the viral genome to confer significant resistance, will generally be more robust to the emergence of resistance in the context of suboptimal adherence or treatment interruption. Such robustness is critical, given...

Arterial Stiffness and Extracellular Matrix

The growing prevalence and associated risk of arterial stiffness provide a major challenge to better understand the underlying causes and the resultant physiological impact of this condition. Structural components within the arterial wall, mainly collagen and elastin, are considered to be major determinants of arterial stiffness. Thus, quantitative and qualitative alterations of collagen and elastin fibers are involved in arterial stiffening that is associated with the aging process and disease states such as hypertension, diabetes, atherosclerosis, and chronic renal failure. Elucidation of mechanisms leading to the above alterations will aid in more specifically targeted therapeutic interventions because currently available cardiovascular medications fall short at reducing the stiffness of the large arteries. Reduction of arterial stiffness will likely have a significant impact on morbidity and mortality of older adults, as well as subjects suffering from cardiovascular and renal...

Management Programs Control Hospital Antibiotic Policy

Antibiotics are used in three general settings hospitals, community, and agriculture. Only hospitals are starting to take responsibility for stewardship. (The Food and Drug Administration is responsible for efficacy and safety, not drug longevity.) Antibiotic management teams now guide prescribing policies of most U.S. hospitals (see Box 7-1). Among their activities is approving only certain antibiotics for hospital use. These antibiotic lists, called formularies, generally include only a few members of each antibiotic class. Formularies enable the entire hospital to take advantage of local infectious disease experts, and formularies help hospitals negotiate discount prices from pharmaceutical suppliers who want their product listed on the formulary.

Does Arterial Stiffness Predict Atherosclerotic Coronary Events

Coronary heart disease is a major cause of death and morbidity. Due to the increased longevity of most developed societies, there is an increasing overlap between arteriosclerosis associated with normal vascular ageing and atherosclerosis associated with cardiovascular risk factors. There is therefore a need for improvements, both in the early identification of individuals at risk, and in cardiovascular risk stratification. Arterial stiffness is an important determinant of cardiovascular risk and can now be measured simply and non-invasively in large populations. This review will therefore focus on the current evidence as to the predictive value of arterial stiffness in relation to coronary events and also on the possible pathophysiological mechanisms linking arterial stiffness and atherosclerosis.

Typeii Diabetes Mellitus

Diabetics with a limited life expectancy, therapeutic control should be primarily aimed at avoiding acute symptoms such as weight loss, polyuria and polydipsia, coma and foot problems. Blood glucose, however, can be tolerated up to 180 mg per 100 ml fasting and 250 mg per 100 ml postprandial and HbAi around 10 . In younger Type-II diabetics, who still have a life expectancy of more than 10 years, with long-term complications of diabetes still to come, the same degree of metabolic control should be achieved as in Type-I diabetics near-normal blood glucose, HbAj lower than 10 and normolipidaemia. In many of these patients, after secondary failure, insulin therapy can be initially combined with oral agents which might promise some metabolic benefits for a limited time range in ca. 50 of Type-II diabetics.

Gene Mutations in Nonneoplastic Diseases

Most common lethal inherited genetic disease among the Caucasian population, affecting almost 30,000 Americans.179181 Treatment advances for CF patients have increased life expectancy to more than 36 years today. 1 79 The molecular basis for the development of CF is mutation of the cystic fibrosis transmembrane conductance regulator (CFTR).182,183 The diagnosis of CF is based on several clinical characteristics, a family history of CF or a positive CF newborn screening test, and mutation in the CFTR gene and or protein.184 The symptomatology of CF is highly variable from patient to patient, possibly owing to differences in CFTR function caused by specific mutations.185187 Given that epithelia in CF patients behave as though they are impermeable to chloride ions,1 88 it was expected that the CFTR gene would encode a chloride channel. However, it was found that the CFTR gene encodes an ABC transporter homologue that actually functions as a chloride channel which is directly activated by...

Mechanisms of action nutrients 651 General nutrition

Although prolonged energy, protein or micronutrient malnutrition may increase an individual's risk of developing cancer, perhaps by reducing the effectiveness of the immune system, life expectancy in societies with large malnourished populations is low, and infectious diseases are more likely to be the principal causes of illness and mortality. In prosperous Western societies, over-consumption of energy, coupled with inadequate exercise, appears to be a major risk factor for cancer. The World Cancer Research Fund report on diet and cancer4 made some general recommendations on food supply, eating and related factors. For individuals, the general advice was to consume nutritionally adequate and varied diets based predominantly on fruits, vegetables, pulses and minimally processed starchy foods. Overweight, defined as body mass index (BMI weight in kg height in metre 2) in excess of 25 is associated with a rise in the relative risk of most cancers, and frank obesity is particularly...

The Biochemistry Of Aging

Life Expectancy versus Maximum Life Span Aging is a fascinating topic that has interested philosophers and scientists for centuries. Indeed, interest in the aging process has markedly accelerated, particularly over the past two decades, primarily due to the realization that not only do the that has interested e aging process has primarily due to the

Clinical Development of CV706 and CV787

A Phase I trial of CV706 was initiated in 1998 at the Brady Urological Institute of the Johns Hopkins Oncology Center under the direction of Jonathan Simons, MD, and Ted DeWeese, MD. The patient population consists of men with locally recurrent prostate cancer with rising PSA levels following definitive external beam irradiation. Men in this category are usually left untreated or receive androgen ablation therapy as serum PSA levels rise significantly above 10 ng mL. On average, these men have a life expectancy of 3 years. The virus was administered under spinal anesthesia using the brachytherapy template

Discuss the pathophysiology of aortic stenosis

Exertion can occur in the absence of coronary artery disease because the thickened myocardium is susceptible to ischemia and the elevated LV end-diastolic pressure reduces coronary perfusion pressure. Life expectancy with symptoms of angina is about 5 years. Once syncope appears, the average life expectancy is 3 to 4 years. Once congestive heart failure occurs, the average life expectancy is 1 to 2 years.

Gastroesophageal Varices

Childs-Pugh Class C cirrhotic patients have a very high operative mortality with emergency shunt surgery and a limited life expectancy secondary to their liver failure. Because of lower procedural mortality, these patients should be managed with TIPS. Childs-Pugh Class A and B cirrhotic patients have a significantly lower operative mortality and longer life expectancy than Childs-Pugh Class C patients. In these patients, the increased durability of surgical shunts relative to TIPS is worth the higher procedural morbidity and mortality of surgery. Patients who are not transplant candidates but have good liver function should have their refractory acute variceal bleeding controlled by emergency shunt surgery. This approach is outlined in Table 3.

People in Famines Generally Do Not Die of Starvation

Although fat people live longer under conditions of voluntary complete starvation, in accord with the predictions of the balance of energy expenditure relative to storage (fasting endurance), these conditions are not necessarily a good model for what happens during natural (or man-made) conditions of famine. In fact, it may come as a surprise to most people to discover that during most famines relatively few of the people that die perish from frank starvation that is, depleting their body reserves to the point where they run out of energy. Perhaps the most comprehensive data available on causes of mortality during famine comes from the Irish potato famine, which hit the island of Ireland between 1845 and 1850. The cause of the famine was a combination of societal and natural disasters. During the period in question the staple diet of the population was almost entirely restricted to a single crop the potato. During the famine years the potato crop was devastated by an infection of the...

Cystic Fibrosis Chronic Lung Infection with P aeruginosa

Aggressive antimicrobial treatment of chronic P. aeruginosa infections in the CF lung improves lung function and life expectancy but the infection is rarely if ever eradicated. The main reason is most likely the biofilm mode of growth, but the frequent occurrence of multiply drug resistant (MDR) P. aeruginosa in CF patients implies that conventional resistance mechanisms also play a role.

Obesity Therapeutics Prospects and Perspectives

Obesity is often mischaracterized as a cosmetic, or life style issue when in fact it is a devastating disease with tremendous health and financial consequences. In the US alone, it has been estimated that there are greater than 300,000 deaths per year (2). This distressing effect on life expectancy is largely related directly to the life threatening co-morbidities of obesity such as non-insulin-dependent diabetes, hypertension, coronary artery disease, and some forms of cancer (3). The less lethal comorbidities associated with obesity include gallstones, osteoarthritis, degenerative arthritis, and apnea. The financial consequences of obesity can be measured in multiple ways as a total cost to society (direct and indirect), estimated percent of total medical cost, and direct value of obesity related medications (4-6). Whichever parameter is chosen to measure the financial impact of obesity, the cost is highly significant to our society.

Posttest discussion points when giving an HIVpositive result

Whilst recognising the seriousness of the diagnosis, you should avoid speculating about a patient's life expectancy, stressing that each individual case is different and that strategies to extend survival and new treatment therapies are being developed and tested at a rapid pace. The fact that they are diagnosed in a first world country will mean that treatment options are readily available and expert care is available.

Antibiotic Discovery Faces a Fundamental Economic Problem

Because pharmaceutical companies, or any company for that matter, cannot survive by developing and producing a product that they know will ultimately lose money, development costs must be reduced, or governments must heavily subsidize the effort. Alternatively, companies could seek new anti-infectives that will severely restrict the emergence of resistance (see Box 10-8) Extending the time before resistance develops should increase the likelihood that development costs will be recovered because sales could be high. Such an alternative has yet to become a focus of drug discovery efforts. We expect the decline in antibiotic discovery to continue until new ways are found to finance antibiotic development or to increase antibiotic longevity.

A brief history of antibiotics

Antibiotics played a major role in defining and developing the nascent pharmaceutical industry of the 1940s and 1950s to a highly successful, scientifically driven enterprise producing a steady stream of life-saving drugs and contributing significantly to expanding human life-expectancy and improving quality of life throughout the developed world 5,6 . From the early 1970s through the middle 1990s, the productivity of antibacterial drug R& D groups enabled the production of a steady stream of new antibiotics to treat bacterial infections. The most common strategy employed throughout this period was to make incremental changes to the chemical structures and formulations of existing drugs to produce next generation drugs with incremental improvements in properties. The changes typically addressed specific issues such as improved potency, spectrum of activity, toxicity profile or a more convenient dosing regimen. One of the important outcomes of this approach was the development of...

Obesity And Abdominal Adiposity

Prospective study of over 1 million adults in the US evaluated the relationship between BMI and cardiovascular mortality as well as all-cause mortality20. The risk of death from cardiovascular disease as well as all causes was noted to increase progressively over the range of overweight to clinically obese patients regardless of age or sex (Figure 7.7)20. One study demonstrated that risk factors for coronary artery disease such as low HDL cholesterol levels, systolic blood pressure, triglycerides, glucose, and serum total cholesterol often cluster with obesity21. The study also demonstrated that a 2.25 kg weight reduction was associated with a 48 reduction in the sum of risk factors for coronary artery disease in man and a similar 40 reduction in women21. A recent study investigated the relationship between being overweight or obese at 40 years of age and life expectancy22. Overweight and obesity were both strongly associated with large decreases in life expectancy, even among...

Immunomodulatory phosphorylcholinecontaining proteins secreted by filarial nematodes

Introduction - Parasitic worms represent an enormous medical problem for humans. Current estimates as to the number of infections world-wide are greater than the global population and one species alone, Ascaris lumbricoides, infects more than a quarter of all humans. A characteristic of infection with these worms is its enduring nature. Infections with parasitic worms are in fact commonly life-long and indeed individual worms may survive for several decades. Such longevity is remarkable given that the worms contain a repertoire of highly immunogenic molecules and dictates that they must have evolved extremely effective mechanisms for evading host immunity. One wide-spread mechanism by which they do this involves actively modulating the host immune system such that it is rendered ineffective. It is generally accepted that an elucidation of the molecular mechanisms and associated targets underlying this immunomodulation, will provide opportunities to develop novel strategies to...

Immunodeficiency Disorders

At present there is no cure for AIDS. Early diagnosis and treatment are vital. Certain medications that are currently available, when used in combination, seem to slow development of the disease. These medications include nucleoside analog reverse transcriptase inhibitors (such as zidovudine, also called AZT), which interrupt an early stage of virus replication, and protease inhibitors (such as indinavir, ritonavir, and saquinavir), which interrupt the same process at a later stage. Although these cocktail drug regimens typically cause unpleasant side effects such as nausea and diarrhea, when started early, they are enabling many people infected with HIV to live longer, more productive lives. Other drugs designed to combat the virus, bolster the immune system, and prevent or treat opportunistic infections that result from HIV infection are now being tested. Research on an AIDS vaccine is also under way. For more information on HIV and AIDS, see page 186.

Mutations of the Amyloid Precursor Protein Gene

An interesting familial mutation has been observed that affects the Ap region of the APP gene and causes an amino acid substitution in APP site 693 (E693Q). Although amyloid bodies are formed, none of the features of AD is present. There are no NFTs, and neither the neocortex nor hippocampus undergoes any significant neuronal loss. Instead, the phenotype associated with APP(E693Q) is severe rupturing (hemorrhaging) of the small blood vessels of the cortex and cerebellum as the result of an accumulation of diffuse Ap amyloid bodies. This condition is called cerebral amyloid angiopathy (CAA) and is quite rare. The CAA APP(E693Q) mutation is inherited as an autosomal dominant trait. Onset occurs between 45 and 55 years of age. Approximately 50 of those with CAA APP(E693Q) die within 12 months after the first serious hemorrhage. Those who live longer experience a series of debilitating strokes. Transfection studies with mutant APP(E693Q) cDNA indicated that there was no increase in the...

A specific health problem smoking

Perhaps the most important final point to make in this chapter is that health is not simply a physical or biological matter. Psychological factors are heavily involved in it in all of its aspects. Stress, anxiety and emotion, in general, all have their effects on the immune system, health in general and in reactions to disease. Although this makes health a more complex matter than it was once thought to be, it also means that various psychosocial factors can be used in order to bring about positive changes to the health of individuals, from dealing with stress and the control of chronic pain through to increased chances of longevity.

Are there any medications that I should adjust or stop taking while Im being treated for osteoporosis

That has been used for years to manufacture estrogen, progesterone, and testosterone. Because DHEA is a precursor of testosterone, sometimes high dosages of it cause male characteristic side effects such as facial hair and acne, although doses around 50 mg or less do not appear to cause these side effects. DHEA has been touted as an anti-aging miracle drug. Its claimed effects include increased energy and better sex drive. Although DHEA is available over the counter, you must discuss its pros and cons with your clinician before trying it. The dosage of DHEA being used in clinical trials is about 150 mg to 200 mg per day. A clinical trial looking at DHEA's effect on Crohn's disease is also being conducted.

Rosa Palasciano Sabrina Capurso Annamaria Gadaleta Antonio Capurso Patrick G Kehoe and Vincenzo Solfrizzi

Vascular Genetic Factors and Human 2.1. APOE Gene Polymorphism and Genes Related to Longevity 3. Inflammation and Immune Response in Human Human Aging can be considered the product of an interaction between genetic, environmental, and lifestyle factors, which in turn influence longevity that varies between and within species 1 . Given the high complexity of the phenomenon, several theories have been proposed providing an insight in the role of genetic and environmental factors in the process of aging 2, 3 .

Aging and Mitochondrial Dysfunction

Demonstrated that specific mutations in mitochondrial genes can cause many pathologies 12-18 , some of which accompany aging. These associations have led to the proposal that mitochondria play causal roles in the aging process, and the acceptance of the oxygen free-radical theory of aging has further reinforced this view, especially as oxygen and mitochondria are intimately related. It can be equally well argued, however, that mitochondria normally function as antiaging agents because dietary restriction and aerobic exercise, which suppress or delay aging and or related pathologies, increase mitochondrial activity and or mitogenesis 19-26 it is loss of certain mitochondrial activities that provokes aging onset 3, 7, 8, 27, 28 . These and other observations have therefore led some to question many of the assumptions underlying the proposed causal roles of ROS and mitochondria in aging and associated pathologies 29-35 . Additionally, it should also be noted that aging also occurs in...

Preparation For Carotid Stenting

As mentioned above, patient selection is critical. Using the standards established in NASCET for measuring the degree of stenosis, patients should have symptomatic disease > 69 or asymptomatic disease > 80 . They should be poor surgical candidates but have a life expectancy > 5 years. Although noninvasive methods can document stenosis, assessment of the degree of stenosis is fairly inaccurate. In NASCET, as well as ACAS, official cervical angio-grams were used to assess the degree of stenosis.

Origin of Altered Proteins

One early explanation of aging was the so-called error-catastrophe theory which posited that an increase in translational errors may cause aging 81 , due to the eventual feedback of errors into DNA replicative enzymes, thereby increasing DNA replication errors and altered (mutant) protein formation. Although the major prediction of this theory, an age-related increase in translational error frequency, has never been realized, it should be pointed out that the theory has not been tested with respect to proteins synthesized by mitochondrial ribosomes 82 . However, it has been shown that decreasing the error frequency of mitochondrial ribosomal protein synthesis increased yeast cell longevity 83 , while increasing the error frequency of cytoplasmic ribosomes in cultured human fibroblasts by paromomycin provoked the onset of cell senescence 84 . Interestingly, the phenomenon of ototoxicity of certain antibiotics has been ascribed to their miscoding effects on mito-chondrial ribosomes...

Post Genomic View of Aging Definitions Theories and Observations

From birth to death, aging is a continuous and extremely complex multifactorial process that involves the interaction of genetic, epigenetic and environmental factors, and in which the incidence of diseases increases as well as the possibility of dying. The variability of the aging phenotype among individuals of the same species as well as the variability in longevity among species strongly suggests the mediating influence of both genetic and environmental factors in dictating the life span. For example, several genetic polymorphisms are known to confer extreme longevity in animal models, and a number of observations suggest that similar polymorphisms may operate in humans. The spectrum of the aging phenotype may vary from disease and disability to absence of pathology and preservation of function. At present, humans over age 65 are more likely to be active and productive than at any other time in history and life expectancy, disability rates, and health and wealth indicators have all...

Management options

Infection, e.g. with fungi or other atypical organisms. Neurological manifestations are especially important to anaesthetists and include neuropathy, encephalopathy, meningitis, focal brain lesions, dementia, myelopathy and myopathy. In addition, HIV-positive subjects' life expectancy is increased by taking prophylactic highly active antiretroviral therapy (HAART). These drugs may cause blood dyscrasias, gastrointestinal disturbances, neurological and hepatic impairment and increased drug metabolism via hepatic enzyme indication. Prior to any anaesthetic intervention all patients must therefore be assessed carefully for evidence of organ system impairment.

Whats the likelihood that I will die from osteoporosis

With life expectancy increasing, the federal government is making recommendations in an effort to help you live out your years in a more healthful manner. By 2010, it is expected that 12 million men and women over the age of 50 will have osteoporosis, and a remarkable 40 million will have osteopenia. Preserving your bone health can help prevent osteoporosis and the fractures that can cause early death. Healthy People 2010, an initiative from the Department of Health and Human Services, challenges Americans to improve their health by engaging in activities that promote their overall well-being. Some of the challenges relate directly to bone health, such as avoiding tobacco and alcohol, as well as increasing activity and eating a healthy diet. For example, one of the goals of Health People 2010 is to reduce the percentage of adult Americans who smoke by half (from 24 to 12 ). Another goal is to double the percentage of adults who exercise 30 minutes daily from 15 to 30 .

Clinical Box 51 Free Radicals and Aging

It has been proposed that aging results partly from accumulated damage caused by free radicals. Most of the support for this theory comes from studies of mice and rats. It has been shown that mice lacking mitochon-drial SOD survive only for a short period and that mice over-expressing mitochondrial catalase (i.e., the enzyme that detoxifies hydrogen peroxide) have increased life spans. These studies support a role for free radicals in aging and also point to the mitochondrion as a primary source of the destructive molecules. There also are some hints that the long life span of humans is related to control of free radicals. For example, it appears that in comparison to mouse cells, human cells have a greater ability to manage damage by free radicals. Another line of evidence that links longevity to decreased free radicals is that rodents and other animals placed on very low calorie diets live longer and show decreased production of superoxides and hydrogen peroxide. Unfortunately,...

Current Role Of Surgical Shunts

The management of a complex disease such as portal hypertension requires a multidisciplinary effort, and each specialist has a defined role and contribution gastroenterologist (overall management of the liver disease, medical management of variceal hemorrhage, sclerotherapy or variceal banding), vascular transplant surgeon (surgical shunting, liver transplantation), and interventional radiologist (TIPS). The treatment of each patient should be selected based on the severity of the underlying liver disease, the amount of functional liver reserve and his life expectancy. There is little doubt that patients with severe liver dysfunction should not undergo surgical porta-systemic shunting as a high likelihood of perioperative mortality, and encephalopathy can be expected. Such patients are best managed with sclerotherapy or TIPS as a bridge to an eventual liver transplantation, which is the definitive treatment for both the portal hypertension, and liver dysfunction. If the patient is not...

Oxidative Stress Yields DNA Damage

Oxidative damage is not necessarily present in significant amounts in the normal brain (Arnett et al. 2005), presumably because mediators of oxidative stress are balanced by endogenous antioxidant systems. In the rodent, under normal physiological conditions, however, increases in basal levels of oxidative DNA damage have been detected in the brain during aging (Cardozo-Pelaez et al. 1999 Hamilton et al. 2001 Rutten et al. 2003). Furthermore, in the aging human brain, DNA damage has been found in the promoter regions of genes encoding proteins that are downregu-lated in the aged brain, suggesting that DNA damage accumulates in the brain over time (Lu et al. 2004). Accumulation of DNA damage during the aging process may contribute to age-related neurodegeneration the extent and consequences, however, of nonpathological DNA damage in the brain have yet to be determined.

Neurofibromatoses Neurofibromatosis Type

The age of onset of NF1 ranges from less than 10 years to 40 years or older. After onset, the severity of the clinical features increases with age. Generally, life expectancy is reduced as a result of complications caused by recurring benign tumors. If malignant tumors develop, the prognosis is poor.

Preparing for Surgery

There are no guarantees when it comes to the results of cosmetic surgery. Be sure that you have realistic expectations about how you hope to look and feel after the procedure. Discuss your expectations fully with your doctor and listen carefully to his or her description of the proposed outcome. Do not expect cosmetic surgery to stop or reverse the aging process. Although cosmetic surgery can enhance your appearance and increase your self-confidence, it will not necessarily match your ideal image or cause other people to treat you differently. The final result may differ from what you have in mind.

Physical Function An Important Geriatric Concept

The number of older persons living with physical disability increases dramatically with increasing age. Data from the US National Health Interview Survey of Disability show that of the women aged 65 years and older, 18.8 needs help with (instrumental) activities of daily living at home, which is 10.9 in men (3). At the age of 85 years or older, 54.8 of the women and 36.9 of the men are needing help with (instrumental) activities of daily living. One of the key paradoxes in gerontology is that although women live longer than men, they live with more physical disability at older age. This is for a large part caused by the fact that the prevalence of nonlethal but disabling chronic diseases is generally higher in older women than in older men.

Laboratory Findings in CR Nonhuman Primates

The longevity data in monkeys remain preliminary. However, previous reports from the National Institute on Aging indicate that CR reduces morbidity, neoplastic diseases in particular 70 , and perhaps even mortality 71 in monkeys. Early in 2002 at the National Institute on Aging, the proportions of both rhesus and squirrel monkeys that had died in the CR cohorts were about one-half that in the controls 72 .

Contexts and Challenges for the Use of New Antibiotics

In the preantibiotic era, some 100 years ago, the three main causes of death in the United States were bacterial infections tuberculosis, pneumonia, and gastrointestinal (GI) tract infections (Wenzel and Edmond, 2000) accounted for 30 of deaths, and the life expectancy was 47 years (Cohen, 2000). At the end of the 20th century in the developed world, only lower respiratory tract infections still ranked in the top 10 causes of mortality. More specifically, for the eight decades spanning 1900 to 1980, infectious disease mortality in the developed world fell from 797 100,000 to 36 100,000, a tribute to improved public health and the impact of antimicrobial therapeutics. But the 15-year interval from 1981 to 1995 saw a rise in mortality rates from that 36 100,000 to 63 100,000 (life expectancy had increased to 76 years), reflecting changes in the patterns of infectious diseases (Cohen, 2000). The developing world had no such success story, with 13 million infectious disease-related deaths...

Antimicrobial Therapy

A number of factors should be considered when choosing appropriate antimicrobial agents. They should be effective against all target organism(s), induce little or no resistance, achieve sufficient levels in the infected site, have minimal toxicity, and have maximum stability and longevity.

Utilization of Composite Rhytidectomy to Correct the Unfavorable Outcomes Following Facelift Surgery

Esthetic Surgery Finger

Many patients have a normal crescentric anatomical pattern on the upper cheek area called a malar crescent (Fig. 42.12). The problem with this excessive orbicularis muscle that may become a malar mound or festoon is that it is made even worse with a simple superior lateral facelift, since it is not changed and is in fact made more obvious. While it appears quite normal on a normal unoperated aging face, it becomes a distinct stigma of previous surgery. Of greater significance is the potential for a deeper concavity of the lower eyelid created by orbital indiscriminate lower-eyelid fat (Fig. 42.13). The triad of an unoperated forehead, hollow lower eyelid, and a lateral sweep is pathogenomoic of previous facelift surgery 15 . Frequently, a second facelift is done to correct this stigma of the facelifted appearance but the same lateral vector technique may enforce the undesirable appearance. The effective tightening of the SMAS, which has more longevity than the operated upper facelift...

Custom joint replacement implants

Rapid Prototyping Implants

Design and fabrication of hip and knee implants are currently being investigated. The proposed concept is to custom design implants based on patient-specific CT data. Since the proposed design of the knee implants involves the use of novel contoured bone-implant interface surfaces, they must be tested on animals before any clinical studies can be conducted on humans. The veterinary school at NCSU is currently performing hip replacements on dogs on a weekly basis using standard implant components. Both a cemented and a cementless hip implant system have been developed at NCSU where the implant components come in several sizes. Currently there are no commercial knee implants available for dogs owing to the number of sizes that would be necessary to accommodate different sizes of dog knees within a breed and between different breeds. The idea of custom designing the implant components for each patient would solve this problem for dogs, and would provide a remedy for the common condition...

Direction of the Traction of the Cutaneous Facial and Neck Flap and its Resection

Versajet Method

Once the cutaneous flap has been pulled, the redundant skin is excised with a knife all around the ear. The amount of traction which is applied depends on the state of the skin and the nature and degree of correction required. It is time to emphasize that rhytidoplasty is a palliative procedure since the aging process does not stop. Fore this reason the operation should achieve a natural and smooth result (Figs. 39.11-39.15).

Benchmarking Its Utility in the Fight Against Antibacterial Resistance

As a result of the recent decline of antibacterial drug development and the increasing number of off-patent agents, fewer large pharmaceutical companies are involved in supporting large-scale surveillance studies. Also, those companies that are developing antibacterial agents are generally more selective about the studies performed and or often have insufficient resources to support these large and expensive programs. In this climate, programs such as the SENTRY Antimicrobial Resistance Program (17), which represents a long-standing program that originally received funding from one sponsor (Bristol-Myers Squibb) and which now receives funding from a number of pharmaceutical companies, is an example of an effective paradigm for a broad-based surveillance program that ensures longevity of data collection.

Section Ii Cardiovascular And Pulmonary Diseases

Until recently, median life expectancy for patients with PPH was two to three years after diagnosis. Predictors of survival include performance in the six-minute walk test (11), pulmonary artery pressure, right atrial pressure, cardiac index and mixed venous oxygen saturation (12). For reasons unknown, the presence of Raynaud's disease is associated with a worse prognosis. Survival is longest in patients who have cardiac output > 2.5 L min and respond favorably to acute vasodilator challenge (13). In contrast, cardiac output < 2.5 L min, left untreated, predicts a survival of only several months. The disease is progressive and has no cure.

Alcoholic versus viral or idiopathic chronic dilated cardiomyopathy DCM

The most prevalent confusion with the alcoholic heart disease caused by thiamine and nutritional deficiency is with viral or idiopathic chronic DCM. Between 20 and 35 of all cases ofDCM are thought to occur because of excessive ethanol intake 25 , However, in both alcoholic and idiopathic chronic DCM, the clinical picture is similar. In the early stages of both categories of congestive heart failure, the patients often show some response to bedrest, salt restriction, diuretics, and digitalis. Afterwards there is slight-to-moderate cardiac dilatation. Still later the heart becomes markedly enlarged. Once cardiac failure appears, life expectancy can be measured in months or, at the most, a few years. Death is usually from heart failure, uncontrolled arrhythmias, or thromboembolism. In both, the electrocardiogram may show conduction disturbances, nonspecific ST-T abnormalities, and even anterior infarction.

The Impact Of Parkinsonism On Healthrelated Quality Of Life

Some analogies can usefully be drawn from Hr-QoL studies in PD. The degree of disability in atypical parkinsonism is at least as great as in PD and depression occurs in all atypical parkinsonian disorders (29,30). It is therefore likely that these factors are also important in atypical parkinsonian disorders. However, these are likely not to be the only difficulties encountered by patients with atypical parkinsonism in whom, frequently, many systems are affected. The impact of features such as greater autonomic dysfunction, higher rate of falls, behavioral changes, or cognitive impairment, will depend on the type of atypical parkinsonism. In addition, the shortened life expectancy, greater disability, lack of response to treatment, associated nonmotor features, cognitive impairment, and behavioral disturbances in atypical parkinsonian disorders will all impact on patients' subjective evaluation of their Hr-QoL. On the other hand, symptoms that occur less frequently in atypical...

Aging and Autophagy of Mitochondria

Macroautophagy involves the formation of autophagosomes containing large portions of cytoplasm or whole organelles bounded by a double membrane which then fuse with lysosomes. This process, sometimes simply termed autophagy, involves nonselective intake of cytoplasmic material for degradation into reusable building blocks. Macroautophagy responds to metabolic cues such as starvation, controlled by the target of rapamycin (TOR) regulatory complex. TOR activity is inhibited by rapamycin. The increased incidence of general protein breakdown may help to explain the beneficial effects of dietary restriction and rapamycin on longevity by suppressing the accumulation of altered proteins and dysfunctional organelles. It is observed, however, that macroautophagy activity declines with age, possibly due to the accumulation of undegradable lipofuscin (age pigment) within the autophagosomes. Lipofuscin is formed spontaneously when partially degraded material (peptides or lipid) becomes...

Sexual Desire and Aging

Older married people are more likely than single people of the same age to report engaging in sexual intercourse. But marriage does not guarantee a partner for life. Health problems that develop over the course of a marriage can interfere with one partner's or both partners' ability to engage in sex. Because men have a shorter life expectancy and women tend to marry older men, women are more likely to be widowed. Nearly 34 percent of women and 7 percent of men are widowed at ages 55 to 59 60 percent of women and only 18 percent of men are widowed at age 85 or older.

Lipoprotein a and Clinical Manifestations of Atherosclerosis

Only nine years after its discovery in plasma as an antigenic trait, a relationship was suggested between lipoprotein(a) and coronary heart disease (CHD) (B6, D2). Moreover, an interesting relationship between longevity and Lp(a) concentrations was reported by Berg (BIO) The frequency of higher Lp(a) levels in very old persons (> 83 years) was lower than in the reference population. The same observation was made by Knapp (K18) in black American men. This

Theories Of Senescence

To date, the only known practical method of extending longevity of mammals is dietary restriction (DR ref. 18). This was first recognized in 1935 by the nutritionist, McCay (19). Actually, it is the restriction of caloric intake that results in prolongation of life in model studies with rodents (18,20). Within reasonable limits, the greater the restriction of calories the longer life expectancy is extended (20). Although in most studies DR has been initiated at the time of weaning of juvenile rodents, DR commenced in young adult or midlife ages also results in life extension (20,21). DR results in a significant retardation of the age-associated decline in immunological competence and a significant lowering of the incidence of tumors in rodents, both of which are well correlated with increased longevity (20,22). The reasons offered to explain this apparently beneficial effect of DR are discussed in Chapter 5. The application of DR to extending longevity in humans at present is out of...

Kathleen Steger Craven

The population in the United States in the 21st century is at greater risk for infections due to increased longevity coupled with more chronic underlying diseases, aggressive medical and surgical procedures, solid organ transplantation, immunosuppressive therapy, and a highly mobile modern society. The current population is also at greater risk of infection from obesity, diabetes mellitus, and cardiovascular diseases. Therapies for various diseases may include antibiotics, steroids, chemotherapy, and a spectrum of monoclonal immune modulators that may increase colonization with antibiotic-resistant bacteria or alter the host immune system. As the result of these pressures, there have been well-documented increases in infections caused by multidrug-resistant (MDR) pathogens both in the community and healthcare settings (2). Some of the more common MDR pathogens include methicillin-resistant Staphylococcus aureus (MRSA), Streptococcus pneumoniae, extended-spectrum...

Altered Proteins and ROS

Interestingly, it has also been found that reduced cytoplasmic protein synthesis suppresses age-related mitochondrial dysfunction 120 , and that decreased protein synthesis has been shown to increase longevity in yeast 121 and Caenorhabditis elegans 122-124 , while methionine restriction (but not other amino acids) suppressed mitochondrial oxidative dysfunction in rats and mice 125 . It is possible that all these examples decrease the generation of error-proteins simply as a result of the lowered overall bulk protein synthesis per cell, thereby decreasing the error-protein load that the chaper-ones and proteolytic apparatus must deal with 77, 126, 127 . Additionally and or alternatively, decreased protein synthesis may induce beneficial alterations in gene expression 128 as it has also been demonstrated that a yeast longevity gene is upregulated when error-protein synthesis is increased 129 , possibly reflecting error-protein-induced expression of stress-proteins (proteases and...

Exercise and Fitness

Lack of exercise is a serious public health problem in the United States, contributing to chronic disease and premature death. Regular physical exercise is one of the most important steps you can take to protect your health and live longer. Each year, millions of Americans experience health problems that could have been prevented or relieved through regular physical activity. Exercise also lowers your risk of developing diabetes, high blood pressure, and colon cancer, and helps to reduce blood pressure in people who have high blood pressure. Exercise helps build and maintain healthy bones, muscles, and joints and prevents back pain by increasing your strength and flexibility and improving your posture. Physical activity also helps to decrease your percentage of body fat by preserving muscle mass. Exercise helps you lose weight and maintain your loss this is another way exercise helps you stay healthy and live longer. It can help


Cambridge geneticist Aubrey de Grey expects that life expectancy will soon extend dramatically. He worked out a very detailed plan to repair all the types of molecular and cellular damage that happen to us over time. Strategies for Engineered Negligible Senescence (SENS) is project to prevent and cure ageing. They should be fully working in mice within just 10 years and it might take only another 10 years to get them all working in humans. The unbelievable legend of Methuselah's age could become true

The Target Viruses

By mutation and selection, evade the blocking effects of a single inhibitor. Therefore, as with tuberculosis, the practical answer is to find inhibitors of a wide range of virus-specific enzymes or proteins and to use them in a patient simultaneously. This search for new drugs will be a continuing need as it is with antibacterials. Similarly, inhibitors of pandemic and epidemic influenza A viruses will need the continuing attention of antiviral chemotherapists. The human herpes viruses (HHV1-8) cause a remarkably diverse range of important diseases and will continue to remain important targets, especially VZV (varicella-zoster virus or shingles), which will reach new importance in a world population with increasing longevity. Common cold viruses and other viruses of the respiratory tract cause pathogenesis in the upper respiratory tract during all months of the year in all countries of the world and hence have economic importance. The eight or so hepatitis viruses, and especially...


Men who are married tend to live longer than men who are single. Does this mean that marriage is the healthiest form of relationship for men Not necessarily. But it does mean that a stable, long-term relationship includes features that positively affect many men's emotional and physical health.


Bacterial types and numbers present in raw milk are influenced by the health of the lactating cow, udder preparation practices, adequacy of equipment cleaning and sanitizing regimens, milk-cooling practices, and the length of time the milk is held before pasteurization. Residual bacterial populations in processed products are determined by initial numbers and types of bacteria in raw milk, time and temperature combination used to process milk, and care taken to prevent recontamination of the pasteurized product. Measures taken to protect raw and pasteurized products from contamination with bacteria contribute to final product quality and shelf life extension.

Chapter Summary

Aging may be viewed as a process that arose early in phylogeny in order to eliminate the competition of postreproductive individuals for limited resources. Because natural selection cannot operate on populations that have passed reproductive activity, those individuals who survived beyond reproductive competence were likely to accumulate random mutations. Although mutations frequently are deleterious, the expression of their adverse effects may require the influence of a hostile environment. Thus, aging may result from a combination of genetic and environmental influences. The remarkable extension of life expectancy in the human population over the last quarter century may reflect, especially, environmental changes coupled with advances in medicine. Recent trends in longevity may suggest that a limit on human life-span is about to be reached.

Fungal Carotenoids

Carotenoids are naturally occurring pigments formed through the isoprenoid pathway that impart attractive color to animals and plants and also have essential biological functions as antioxidants, membrane stabilizers, and as precursors to essential metabolites such as vitamin A. They are biosynthesized as hydrocarbons (carotenes) and as oxygenated derivatives of carotenes (xanthophylls). Various fungi produce carotenoids of biotechnological interest including (3-carotene, lycopene, and astaxanthin (see appendix for systematic names). Compared to other groups of organisms that have been evaluated including animals, terrestrial plants, and prokaryotes, several fungal groups have the ability to produce and accumulate intracelullarly remarkably high levels of carotenoids, a property that they share with certain microalgae. Thus, fungi and microalgae appear most promising for industrial production of carotenoids. Escherichia coli, other eubacteria, archaebacteria, and plants have also been...

Carer Burden

It is not only the lives of patients that are severely affected by the chronic progressive disease course, by decreased life expectancy, and by the multiple consequences of atypical parkinsonian disorders the lives of each family member and, particularly their carers, are also affected. It is likely that atypical parkinsonian disorders affect carers' physical functioning (e.g., caring affecting the carer's own health), emotional well-being (e.g., response to change in role, feelings of hopelessness and depression), and social functioning (limitations on social life), but no studies to date have assessed the different aspects of caregiver burden in these disorders. However, one study investigated the correlates and determinants of carer burden in PSP (35). In this study, the impact of PSP on carers increased with advancing disease severity and disability. Interestingly, this was most pronounced in the first 18 mo after diagnosis, but carer burden plateaued after this initial increase....

Unoperated Forehead

In most facelift surgeries today, the forehead lift is not a consistent part of facial rejuvenation. Since many surgeons and many patients omit this procedure for various reasons, while a patient may undergo a subcutaneous facelift with minimal changes in their early 40s, it would be illogical to assume that the changes are long-lasting. If they are long-lasting then one would agree that the unoperated forehead will become more ptotic, thereby creating a disharmonious appearance in time. On the other hand, if the facelift is considered a light procedure with a short longevity, then the patient normally becomes disenchanted with the results which accomplish little of what was expected. Unfortunately, many patients have had an excessive amount of skin removed from the upper eyelid, making a forehead lift often impossible since eye closure would be a problem.

Old age and death

There are obvious changes that occur with advancing years, both physically and psychologically. One way of looking at such changes is that they either represent or reflect a growing disengagement with life in general or, perhaps, a disengagement with one's own capacities to deal with life. This might well be so for some people as they age. However, an alternative way of looking at the ageing process is that disengagement is forced on the person through lowered physical capacities, retirement and or illness. In spite of this, with increasing age, some people strive to become even more involved with life in spite of whatever decline they might be subjected to.


Iron supplementation affords a relatively simple opportunity for anemia correction depending on the underlying disease. The decision to undertake upper and lower endoscopy, with the attendant discomfort and difficulty of preparation for disabled or confused patients should be made in the context of the patients overall quality of life and estimated remaining life expectancy. There are no studies available that have reported on underlying causes of iron deficiency in older long-term care residents.


It is evident from the preceding discussion that inflammation is a complex multifactoral process in which it is extremely difficult to pinpoint the initiating event. Although advances in molecular biology and laboratory techniques have significantly improved our fundamental understanding of inflammation, it is apparent that the exact biochemical mechanisms involved in this process remain unclear. Lack of understanding has contributed to a paucity of treatment strategies to control inflammation, especially low-grade systemic inflammation seen in CHD, metabolic syndrome X, hypertension, etc. Studies have shown that low-grade inflammation plays a significant role in many of these hitherto believed to be degenerative conditions. It is not yet clear whether low-grade systemic inflammation occurs with the aging process. If so, it will be interesting to study whether suppressing low-grade systemic inflammation can slow the aging process itself. Because inflammation is a fundamental process...


An HC-Ad vector expressing the human al-antitrypsin gene was used in several instructive experiments. Using the loxP helper virus production system, an HC-Ad vector was generated containing the 19-kb genomic human al-antitrypsin locus that included both the macrophage and liver-specific promoters, all exons and introns, and the natural polyadenylation signal 2 . al-Antitrypsin antagonizes neutrophilic elastase and is abundantly expressed in hepatocytes and at a lower level in macrophages. Expression in the two cell types is regulated by different tissue-specific promoters. Currently, al-antitrypsin-deficient patients have a shortened life expectancy due to emphysema. Patients are treated with weekly injections of human al-antitrypsin purified from human plasma.

Aging Heart

Biogerontology has become attractive to biologists in the past decade. Normal human and animal cells have a finite capacity to replicate and function whether they are cultured in vitro or transplanted as grafts in vivo. This phenomenon has been interpreted to be aging at the cellular level. Alterations in the organization and mobility of cell membrane constituents of cultured rat heart myocytes (53) appear a general phenomenon of aging cells. The aging heart exhibits diastolic dysfunction and increased stiffness. Evidence shows that aging affects the passive mechanical properties of single cardiac myocytes isolated from the hearts of 4-mo young and 30-mo old rats (54). Progressive loss of cardio-myocytes occurs during the aging process and may cause heart failure. A recent study showed that intramyocardial transplantation of mouse ESCs improved cardiac function in aging old rats (55). Mouse ESCs labeled with GFP were injected into myocardium of aged rat hearts. Compared with the young...

Experimental Models

When female and male animals are evaluated side by side, a male phenotype of ischemic sensitivity can be uncovered. A remarkable rodent study of more than 2000 genetically hypertensive and stroke-prone animals showed that life expectancy is longer in the female than in the male. Evidence of cerebral hemorrhage and vascular lesions was absent in females until an advanced age (4). These early observations mimic human epidemiology. Furthermore, outcome from brain injury is clearly sex linked in standard animal models. Female rats and mice of many different inbred and outbred strains sustain smaller tissue damage and improved functional outcome from focal or global cerebral ischemia than do males for an equivalent insult. Similarly, male animals sustain greater injury than do age-matched females after traumatic brain injury or Similar sex specificity can be modeled in cell culture when background sex steroids are removed from the media. For example, female neurons tolerate toxic dopamine...

Tumor Metastasis

It would be surprising if there were only a few common gene mutations that controlled metastasis in all cancers. It is more likely that different combinations of these mutations occur in various kinds of tumors. The possibility of glioma-specific metastatic changes has been noted. Gliomas are extremely invasive cancers. About 20,000 new cases are diagnosed each year in the United States, and, despite various therapeutic regimens, life expectancy is at best two years. The basis for glioma invasiveness is not known. However, some gliomas produce a protein that binds to the major component of the extracellular matrix in the brain and, presumably, facilitates the movement of glioma cells through this structure. In other words, this protein lays down a path for glioma cells. Other glioma cells have a chloride ion channel not found in any other cell type, including normal glia cells. This glioma-specific ion channel may pump water out of the glioma cells, making them slender and able to...


The results of this last study raise key questions, viz. (a) how does LPS communicate with opioid receptors in the central nervous system and (b) how do those opioid receptors communicate with splenic MPs Add to those questions a further question how does aging affect opioid receptors and the production of endogenous opioids It is clear that there is a great deal yet to be learned about the in vivo regulation of MP antimicrobial defenses and how it all is affected by the aging process.

Usa 19861989

Hutchinson et al. (2006) conducted an incidence-based COI analysis to estimate the lifetime cost of HIV AIDS resulting from new infections diagnosed in 2002. Having used data from the HIV AIDS Reporting System of the Centers for Diagnose Control and Prevention, stages of disease at diagnoses and the proportion of cases by race ethnicity were determined. The authors estimated provider costs and mortality-related productivity losses were estimated using data on cost, life expectancy, and antiretroviral therapy from literature. The authors estimated the costs of new HIV infections in the United States in 2002 at US 36.4 billion, composed of US 6.7 billion in medical costs and US 29.7 in productivity losses, whereby the medical costs per case were highest for whites (US 180,900) and lowest for Afro-Americans (US 160,400).


The role of ADARs in non-physiological settings, of both individual and combined ADAR deficiency, has not been significantly explored. Studies in humans have yielded interesting associations of human traits with modifications of ADAR family members. Recent studies from human cancer suggest roles for ADAR proteins in both solid and hematological tumors (Ma et al. 2011 Maas et al. 2001). Observations of altered editing activity in tumors, both increased and decreased, highlight a potentially fascinating role for these enzymes in the diversification of the tumor proteome and regulation of tumor transcription through effects on miRNA pathways (Shah et al. 2009). Ongoing improvements in the modeling of human cancer in the mouse and siRNA shRNA technologies lend themselves to a functional assessment of the contribution of ADARs to cancer pathogenesis. Genetic association studies of human centenarians have identified variations in ADAR2 that are associated with longevity (Sebastiani et al....

Relevance to Humans

The effects of CR on longevity in humans have not been evaluated directly. Kagawa et al. examined a proportion of centenarians in Okinawa Prefecture compared with those in other regions of Japan 78 . Okinawa residents have a in height. After adjustment for race, cigarette smoking, income, and body mass index, the relative risk of cancer in several organs is increased 1.5- to 1.6-fold with height. In particular, the colorectal cancer risk for men above 178.6 cm in height is significantly increased by 2.1-fold compared with that for men below 169 cm in height. Moreover, it has been suggested that a large body size and fatness, as measured by adult stature, body weight, and body mass indices, are positively related to a variety of cancer risks, including breast, colorectal, prostate, endometrial, kidney, and ovary 80 . These studies support associations among calorie intake, body size and disease, and perhaps, ultimately, longevity. As shown in Fig. 12A-C 73 , three of the most robust...

Bloom Syndrome

Bloom syndrome (BS) is a rare autosomal recessive disorder characterized by short stature, immune deficiency, redness and often infections as a result of localized capillary expansions and lesions (telangiectasis), primarily of the cheeks and nose, creating the so-called butterfly pattern, sensitivity to sunlight, and increased occurrence of a wide range of cancers, including lymphomas, leukemias, and laryngeal, cervical, and gastrointestinal carcinomas. Life expectancy is not much longer than 50 years. In contrast to cultured normal cells, those from BS patients have large numbers of chromosome abnormalities, such as deletions, duplications, broken chromosomes, and unusual chromosome configurations. An interesting chromosome phenomenon called sister chromatid exchange (SCE), which entails recombination between chromatids of duplicated chromosomes, is commonly observed in cultured BS cells. In addition to chromosome abnormalities, the rate of gene mutation is about 10 times higher in...


Is there any conclusion that we can draw With all carefulness and in due respect to the strong differences between countries, we can state that the reduced costs of hospitalization justify the high cost of HAART in countries where hospitalization and long-term care are provided to all HIV AIDS patients. In countries with low hospital services (e.g., developing countries) this might be different. On the contrary, HAART is strongly increasing the number of years for which we have to finance this expenditure as the life expectancy is strongly increasing. The lifetime provider costs have to be compared with the reduced lifetime indirect costs of HIV AIDS. In countries with a high gross national product, we can conclude that the reduction of indirect costs due to HAART is higher than the increase of lifetime provider costs so that HAART seems a wise investment - not only from a humanitarian, but also from an economic point ofview. In countries with a low gross national product and, in...

Scientific Issues

Whether arsenic is a trace element essential to human health remains a subject of debate. However, many studies have proved the potential beneficial effects of arsenic (ATSDR, 1998). In traditional Chinese medicine, the arsenic compound Xionghuang(AsS) was recorded as one of the superior materials in 'Bencaojing', a famous classic work of pharmacology written during the Ming dynasty. It is reported that arsenous acid or arsenic trioxide (As2O3) is effective in cosmetology, longevity and is often used against many diseases such as psoriasis, syphilis, rheumatosis, and trypanosomiasis (Chen et al., 1995). It was in the 1970s in China that As2O3 was introduced into the treatment of acute promyelicytic leukemia (APL) and it showed a striking effectiveness. A clinical complete remission rate was reported (Sun et al., 1992 Zhang et al., 1996) from 65.6 to 84 with treatment (10 mg day, intravenous infusion for 29 to 60 days). In vitro studies suggested that As2O3 may induce the apoptosis of...

Secondary Facelift

Mouth Reconstruction Surgery

Even celebrities in our profession - the best plastic surgeons in the world - are not able to stop the biological clock. Very good results after rejuvenative procedures are subject to the ageing process and these faces will lose their freshness and attractiveness as time goes by. In well-performed rhytidoplasties we will have fewer problems from facelift surgery, even after 15 or 20 years. Sometimes it could be sufficient to perform only a mini or a minimal-invasive, deep-intensive (MIDI) facelift in patients of even advanced age, if the first surgery was done well.

Age Group

Darwin Tubercle

Although extensive undermining of the SMAS was performed in an earlier period, it has been noted that plication of this structure in the same direction as the skin flaps, with repositioning of the malar fat pad, has given satisfactory and natural results (Fig. 40.7). The durability of this maneuver is relative to the individual aging process. Tension on the musculo-aponeurotic system allows support of the subcutaneous layers, corrects the sagging cheek and reduces tension on the skin flap.

Cystic Fibrosis

The significance of chloride pumps becomes especially evident in cystic fibrosis (CF), a hereditary disease especially affecting white children of European descent. CF is usually caused by a defect in which cells make chloride pumps but fail to install them in the plasma membrane. Consequently, there is an inadequate saline layer on the cell surface and the mucus is dehydrated and overly sticky. This thick mucus plugs the ducts of the pancreas and prevents it from secreting digestive enzymes into the small intestine, so digestion and nutrition are compromised. In the respiratory tract, the mucus clogs the cilia and prevents them from beating freely. The respiratory tract becomes congested with thick mucus, often leading to chronic infection and pulmonary collapse. The mean life expectancy of people with CF is about 30 years.

Ageing Antiageing

The American molecular biologist Leonard Hay-flick has discovered that the life expectancy of every creature depends on the maximum ability of its cells to divide. He discovered that the human cell is able to divide 40-60 times. After that our biological clock runs down. For mice, for example, this number is 28, and for tortoises it is 120. The only cells which do not obey this rule are cancer cells. Will we learn how to prolong life from cancer cells Ageing is not very pleasant, but it is the only known way to live longer is an aphorism by Sent Beuve. Apart from energy and productivity, memory and mental concentration also dwindle in old age. The state of health deteriorates altogether because the human immune system can no longer distinguish self from foreign. This gives rise to autoimmune reactions disarray prevails in the organism like a kind of civil war. A cynical gerontologist once said that age is the only disease from which you cannot expect to recover.

The Neck

The delineation of the cervicomandibular angle plays an important role in the appearance of the attractive, youthful neck 11, 12 . Occasionally, patients are more concerned with the appearance of their necks than that of their faces. As a direct continuation of the aging process of the lower face, the aging neck is mainly attributed to loss of platysmal tone, loose skin, together with periplatysmal fat deposits.

Facial Surgery

As they age, some men seek to improve the appearance of their face and neck through cosmetic surgery. Facial surgery covers a number of different procedures, including a facelift and forehead lift, eyelid surgery, nose surgery, facial implant surgery, and refinishing treatments for facial skin (such as chemical peels and dermabrasion). Sometimes two or more of these procedures are performed at the same time. Although facial surgery cannot reverse the aging process, it can give the face a younger, rejuvenated look that can increase your self-confidence and sense of well-being. The aging process causes the skin of the eyelids to droop, and fat often begins to accumulate above and below the eyes, producing bags. Eyelid surgery (known medically as blepharoplasty) can be used to alleviate these age-related changes. Now the second most common type of plastic surgery performed on men, eyelid surgery can give you a younger appearance but will not remove crow's-feet or other wrinkles from...

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Anti Aging Made Easy

When it comes to reducing wrinkles, you really have to take your needs seriously. There are a number of factors that play a role in the health and well being of your skin. It is often hard to understand how products work and why they may not work even if they promise to do so. If you are considering wrinkle creams and a regimen of facelifts, you may go broke in the process. Before you do all of that, consider going through a process of determine the very best solution for your needs.

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