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The relative lengths of individual telomeres are defined in the zygote and strictly maintained during life.

Previous studies have indicated that average telomere length is partly inherited (Slagboom et al., 1994; Rufer et al., 1999) and that there is an inherited telomere pattern in each cell (Graakjaer et al., 2003); (Londoño-Vallejo et al., 2001). In this study, we quantify the importance of the initially inherited telomere lengths within cells, in relation to other factors that influence telomere length during life. We have estimated the inheritance by measuring telomere length in monozygotic (MZ) twins using Q-FISH with a telomere specific peptide nucleic acid (PNA)-probe. Homologous chromosomes were identified using subtelomeric polymorphic markers. We found that identical homologous telomeres from two aged MZ twins show significantly less differences in relative telomere length than when comparing the two homologues within one individual. This result means that towards the end of life, individual telomeres retain the characteristic relative length they had at the outset of life and that any length alteration during the lifespan impacts equally on genetically identical homologues. As the result applies across independent individuals, we conclude that, at least in lymphocytes, epigenetic/environmental effects on relative telomere length are relatively minor during life.

Age Factors↗

Life extension versus improving quality of life.

There are two principal directions in ageing research: (i) the quest for understanding the mechanisms that determine the length of life and the use of such knowledge in order to find a potentially life extending treatment and (ii) the attempt to improve the quality of life in the elderly by reversing or preventing functional decline of different tissues without primarily extending life span. This chapter addresses the importance of assessing the potential impact of interventions on quality of life rather than extending life.

Aging↗

Contribution of cause-specific mortality to changing sex differences in life expectancy: seven nations case study.

During the last two decades some industrialized nations witnessed varying degrees of constriction in their sex gaps in overall life expectancy. We investigate this development by paying particular attention to the contributions of major causes of death to the change in the difference between 1970 and 1990. The analysis is based on the experiences of seven nations: Australia, United States, Sweden, England and Wales, Portugal, Hungary, and Japan. In the first four countries the gap has been narrowing during the last twenty years; in Hungary and Japan, the difference remains substantial and continues to expand; in Portugal the situation is characterized by a slowdown in the amount by which the sex gap is expanding over time. We apply decomposition analysis to answer the following questions: (1) What is the relative contribution of major causes of death to sex differences in average length of life within broad age categories? (2) How do the contributions of age and cause of death vary across time to either widen or narrow the sex gap in survival? (3) How do the patterns of cause contribution vary across societies?

Adolescent↗

Are causes of death predictable?

A random sample of death records of adult males from 1967 to 1970 was chosen from the South Australian Registry of Births, Deaths, and Marriages. The natural parents of these individuals were identified by cross-reference to birth certificates, and an extensive search was made of the death records for these parents. In this manner random families were selected for which, where possible, the cause of death and length of life of each family member were determined. From the information pertaining to the stated cause of death, each individual was assigned to one of five death categories.

Adult↗

Absence of strong heterosis for life span and other life history traits in Caenorhabditis elegans.

We have examined crosses between wild-type strains of Caenorhabditis elegans for heterosis effects on life span and other life history traits. Hermaphrodites of all wild strains had similar life expectancies but males of two strains had shorter life spans than hermaphrodites while males of two other strains lived longer than hermaphrodites. F1 hermaphrodite progeny showed no heterosis while some heterosis for longer life span was detected in F1 males. F1 hybrids of crosses between two widely studied wild-type strains, N2 (var. Bristol) and Berg BO (var. Bergerac), were examined for rate of development, hermaphrodite fertility, and behavior; there was no heterosis for these life history traits. Both controlled variation of temperature and uncontrolled environmental variation affected the length of life of all genotypes. Significant G x E effects on life span were observed in comparisons of N2 and Berg BO hermaphrodites, or N2 hermaphrodites and males, or N2 and a Ts mutant strain (DH26). Nevertheless, within an experiment, environmental variation was minimal and life spans were quite replicable.

Animals↗

Quality of life after organ transplantation.

Organ transplants are being conducted with increasing frequency. It is generally known that these procedures increase length of life, but less is known about the quality of that life. In this paper, the literature pertaining to quality of life of patients with kidney, pancreas, heart, heart-lung, liver and bone marrow transplants is reviewed. On the basis of this review, it seems that quality of life after kidney and heart transplantation is very good, when compared to the pretransplant state. However, more research is required to examine quality of life of recipients of other types of transplantation. There are many issues that pertain to measurement of quality of life that remain to be addressed. These include: definitions of quality of life, dimensions of quality of life, expectations of quality of life and clinical assessment of quality of life.

Adult↗

[Free radical-related processes of mitochondrial aging].

Mitochondria are particularly susceptible cellular organelles to damage caused by free oxygen radicals. The authors explain certain processes taking place during ageing and leading to death in relation to mitochondrial ageing: an inverse correlation between the value of the basal metabolism rate and life span, the effect of antioxidant addition to the diet on body mass and length of life, the exponential type of the mortality curve as a function of age, the favourable effect of limited calorie content of the diet on life span and development of degenerative diseases.

Aging↗

Trends in prostate cancer survival in Sweden, 1960 through 1988: evidence of increasing diagnosis of nonlethal tumors.

BACKGROUND: The incidence of prostate cancer has increased during the past 30 years but has been paralleled by increases in survival rates from this disease, despite the absence of documented major improvement in curative treatment. Since a high prevalence of microscopic prostate cancer has been observed in autopsied men and because many prostate cancers may never surface clinically, increased diagnostic activities might have led to increased detection of less aggressive tumors. PURPOSE: This study was conducted to elucidate whether the trends in prostate cancer incidence and patient survival may be due to increasing diagnoses of nonlethal tumors. METHODS: We analyzed a population-based cohort comprising all cases of prostate cancer (n = 80,901) detected in Sweden during the period of 1960 through 1988. Five hundred eighteen patients (0.64% of the total number) who could not be followed because of emigration or an incomplete national registration number were excluded. Observed and relative survival rates were calculated for the entire cohort of 80,383 assessable patients per 5-year age group in 5-year periods of diagnosis and according to diagnostic method and were compared between geographic areas with differences in incidence rates. To estimate the independent effects of these determinants, multivariate analyses were performed. RESULTS: For the 80,383 patients with complete follow-up, the 10- and 20-year observed survival rates were 17.5% (95% confidence interval [CI] = 17.2%-17.9%) and 3.5% (95% CI = 3.2%-3.7%), and the relative survival rates were 41.1% (95% CI = 40.3%-41.9%) and 28.6% (95% CI = 26.5%-30.1%), respectively. Relative survival rates improved markedly over time; 10-year relative survival rates increased from 29% (95% CI = 27%-31%) among case patients diagnosed in 1960 through 1964 to 45% (95% CI = 43%-46%) among those diagnosed in 1975 through 1979. Relative survival rates leveled off after about 18 years at 18% (95% CI = 15%-20%) among patients diagnosed in 1960 through 1964 and at 31% (95% CI = 28%-34%) among those diagnosed in 1970 through 1974. An even more favorable outlook was observed in those case patients diagnosed later. In areas with a high or low incidence of prostate cancer, the 10-year relative survival rates were 45% (95% CI = 44%-47%) and 36% (95% CI = 34%-38%), respectively. In the early 1960s, the calculated loss of life expectancy after diagnosis varied from about 68% (95% CI = 61%-75%) of the expected length of life in the youngest age group to about 48% (95% CI = 46%-50%) in the oldest age group. From 1960 through 1964 to 1985 through 1988, the loss of life expectancy decreased by more than 50% in all age groups. The differences in relative survival rates between age groups were small, with a gradual decrease in age groups more than 60-64 years of age. CONCLUSIONS: Most of the great temporal improvement and geographic variation in survival rates are quantitatively consistent, with likely increases in the rate of detection of nonlethal tumors. IMPLICATIONS: The increase in relative survival rates must be taken into consideration when evaluating the outcome of treatment of prostate cancer, since nonrandomized comparisons may be confounded by time trends. Diagnosis of nonlethal tumors raises concerns because the individual would suffer from the psychologic burden of a cancer diagnosis without any therapeutic benefit.

Age Distribution↗

[Cost of pharmacologic treatment and their determinants in ambulatory care of cystic fibrosis patients].

Life expectancy of cystic fibrosis (CF) patients has improved following the introduction of modem therapies. Length of life has been most important determinant of cost of medical care in each population. The aim of this study was to evaluate the cost of pharmacologic treatment and their determinants served by patients and medical insurance. Medical records of our CF center patients from year 2003 were analysed. The annual cost of pharmacologic treatment in our patients in 2003 averaged PLN 26595.91; of total costs 74% were from DNase, 7% from drugs classified as "other", 6.2% from pancreatic enzymes. Individual annual costs served by patients averaged from PLN 979.67 to 10805.57 (mean PLN 6059.63). Mean annual cost "per patient" served by medical insurance averaged PLN 26595.91; 70% of costs were from DNase, 15% from inhaled corticosteroids and bronchodilators. 68% of drug costs were served by medical insurance, 32% by patient. We found significant correlation between cost served by patients (p1), by medical insurance (p2) and age (p1, p2<0.0001) and severity of disease--defined based on percent expected FEV1 (p1=0.006; p2=0.001). Severity of disease and patients age were important determinants of pharmacologic treatment cost in CF patients.

Ambulatory Care↗

Tooth microstructure tracks the pace of human life-history evolution.

A number of fundamental milestones define the pace at which animals develop, mature, reproduce and age. These include the length of gestation, the age at weaning and at sexual maturity, the number of offspring produced over a lifetime and the length of life itself. Because a time-scale for dental development can be retrieved from the internal structure of teeth and many of these life-history variables tend to be highly correlated, we can discover more than might be imagined about fossil primates and more, in particular, about fossil hominids and our own evolutionary history. Some insights into the evolutionary processes underlying changes in dental development are emerging from a better understanding of the mechanisms controlling enamel and dentine formation. Our own 18-20-year period of growth and development probably evolved quite recently after ca 17 million years of a more ape-like life-history profile.

Animals↗

Telomere length in the newborn.

Telomere length is similar in different organs of the human fetus but variable among fetuses. During extrauterine life telomere length is highly variable among individuals and longer in women than men. In the present work we addressed the following questions: 1) Are there sex-related differences in telomere length at birth? 2) Is there synchrony (i.e. correlation in length) of telomeres in tissues within the newborn? 3) Is the variability in telomere length among newborns as large as that in adults? We studied normal male and female newborns who donated DNA samples from three sources: white blood cells, umbilical artery, and foreskin. Telomere length was measured by the mean length of the terminal restriction fragments (TRF). TRF length was not different between male and female newborns. It was highly synchronized among the DNA samples from white blood cells, umbilical artery and skin within individual donors but exhibited a high variability among donors. We conclude that there is no evidence for the effect of sex on telomere length at birth, suggesting that longer telomeres in women than men arise from a slower rate of telomeric attrition in women. The variability in telomere length among newborns and synchrony in telomere length within organs of the newborn are consistent with the concept that variations in telomere length among adults are in large part attributed to determinants (genetic and environmental) that start exerting their effect in utero.

Adolescent↗

[Results of quality of life research in chronic psychiatric patients].

This article resumes the most important results of quality of life research on chronic mentally ill patients and argues for the importance of this perspective of evaluation-research. Chronic mentally ill persons experience less quality of life than the general population. Rehabilitation-programs improve the quality of life of chronic mentally ill patients. There is a covariation between better quality of life and length of the interval without being recidivous. Patients of community based programs report a better quality of life than long-term psychiatric inpatients. Finally some open questions and problems concerning quality of life research on the chronically mentally ill are discussed.

Chronic Disease↗

Problems and solutions in calculating quality-adjusted life years (QALYs).

The quality-adjusted life-year (QALY) is a measure of the value of health outcomes. Since health is a function of length of life and quality of life, the QALY was developed as an attempt to combine the value of these attributes into a single index number. The QALY calculation is simple: the change in utility value induced by the treatment is multiplied by the duration of the treatment effect to provide the number of QALYs gained. QALYs can then be incorporated with medical costs to arrive at a final common denominator of cost/QALY. This parameter can be used to compare the cost-effectiveness of any treatment. Nevertheless, QALYs have been criticised on technical and ethical grounds. A salient problem relies on the numerical nature of its constituent parts. The appropriateness of the QALY arithmetical operation is compromised by the essence of the utility scale: while life-years are expressed in a ratio scale with a true zero, the utility is an interval scale where 0 is an arbitrary value for death. In order to be able to obtain coherent results, both scales would have to be expressed in the same units of measurement. The different nature of these two factors jeopardises the meaning and interpretation of QALYs. A simple general linear transformation of the utility scale suffices to demonstrate that the results of the multiplication are not invariant. Mathematically, the solution to these limitations happens through an alternative calculation of QALYs by means of operations with complex numbers rooted in the well known Pythagorean theorem. Through a series of examples, the new calculation arithmetic is introduced and discussed.

Cost-Benefit Analysis↗

Effects of hemodialysis dose and membrane flux on health-related quality of life in the HEMO Study.

BACKGROUND: It has been widely supposed that high dose and high flux hemodialysis would affect the quality as well as the length of life of patients treated by maintenance hemodialysis. The HEMO Study examined changes in health-related quality of life as a secondary study outcome. Specific hypotheses were that study interventions would affect physical functioning, vitality, Short Form-36 Health Survey (SF-36) physical and mental component summary scores, symptoms and problems associated with kidney disease, and sleep quality. METHODS: At baseline and annually, subjects responded to both the Index of Well-Being and the Kidney Disease Quality of Life-Long Form questionnaires. The interventions were assessed on the basis of their average effects over 3 years. RESULTS: At baseline, the SF-36 physical component summary score was lower than in healthy populations, but the mental component score was nearly normal. Over 3-year follow-up, physical health continued to decline; mental health and kidney disease-targeted scores remained relatively stable. The high dose hemodialysis intervention was associated with significantly less pain (4.49 points, P < 0.001) and higher physical component scores (1.23 points P= 0.007), but these effects were small compared to the natural variability in scores. High flux membranes were not associated with statistically significant differences in health-related quality of life. CONCLUSION: The HEMO Study results demonstrate the marked burden of chronic kidney failure and hemodialysis treatment on daily life. In this trial among patients undergoing maintenance three times a week hemodialysis, the SF-36 physical component summary score and pain scale showed significant but very small clinical effects favoring the higher dialysis dose. No clinically meaningful benefits or either the dose or flux interventions were observed for other indices of health-related quality of life.

Aged↗

[Analysis of eyeball development in children between the fourth month and seventh year of life with regard to eyeball length, refraction value and fundus].

An ophthalmologic screening of three-month-old infants was conducted between 1990 and 1993 in the province of Szczecin. The screening was aimed at early detection and treatment of vision defects and diseases of the eye. Attention was also focused on the appearance of the eyeballs. Approximately 50% of children had a retina of more or less "reduced density". The fundus appeared much like in the case of near-sightedness, raising the question whether such eye would continue towards myopia or would this just be a morphological trait of immature retina which will disappear with growth and development of the eyeball. The children were selected among those reporting for ophthalmologic screening and were divided into four groups: I--children with retina of "reduced density" and near-sightedness in the family (at least one parent had myopia), 45 children--90 eyes; II--children with retina of reduced density, whose parents did not have myopia, 45 children--90 eyes; III--children without changes in the fundus and with near-sightedness in the family, 30 children--60 eyes; IV--children without changes in the fundus, whose parents did not have myopia, 30 children--60 eyes. An additional group consisted of children without family history of near-sightedness, in whom myopia was -5.0 D sph or more during skiascopy with cycloplegia when the child finished six months of life (10 children--20 eyes). The following was examined in all children after three months of life: pupillary reflexes, fixation, anterior segment of eyeball, eyeball length, fundus, intraocular pressure, and refraction. The examination was repeated when the children finished three years, and six years ten months of life. Skiascopy was performed with prior cycloplegia. Statistics were done using Mann-Whitney test for unpaired and Wilcoxon's test for paired results. The following conclusions were made: 1. Length of the eyeball was not related to the appearance of fundus or family history of myopia (Tab. 1). Growth of the eyeball could be divided into two periods. The first was fast, lasting until the end of the third year of life. The second was slow and by the end of the seventh year, growth was almost complete. In children with inborn near-sightedness, the eyeballs were already longer in the fourth month of life. 2. Average size of refraction after cycloplegia in six-month-old infants does not depend on the appearance of eye fundus or family history of near-sightedness. Between six months and three years of life, a limited increase in refraction took place, whereas between the fourth and seventh year of life a decrease was observed. This decrease was significantly greater in children with a family history of near-sightedness. In children with inborn near-sightedness, there was no increase in refraction and decrease proceeded at a faster pace. In six-month-old infants, reversed astigmatism predominated, but between the seventh month and fourth year of life it declined and between the fourth and seventh year its axis changed (Tab. 3 and 4). 3. "Reduced density" found in three-month-old infants is a morphological trait of the retina and does not predispose to near-sightedness. It occurs more often in children with blue or light gray color of the iris, i.e. with little pigment in the stroma (Tab. 6). In most cases, "reduced density" disappeared before the end of the third year of life (Tab. 5). In children with inborn near-sightedness it was not possible to assess on the grounds of the eye speculum whether the observed reduced density was caused by lack of pigment in the pigmented layer of the eyeball or by near-sightedness, or both.

Child↗

Medical Economics and Quality of Life: Analysis of Factors That Influence the Perception of Medical Cost by Post-surgical Breast Cancer Patients.

Recently, the importance of achieving a balance in terms of length of life (LL), quality of life (QOL) and medical costs has been emphasized in the evaluation of cancer treatment, and it is also said that the cost should be seen from the viewpoints of both the society and the patient. Few studies, however, have been performed to investigate how the patients bear the cost and the influence of this factor. Therefore, in the present study we examined the perception of medical care cost (PMC) in 83 non-recurrent post-surgical breast cancer patients. The factors that influence the PMC were analyzed by univariate and multivariate analyses using the variables representing QOL, sociodemographic and clinical characteristics, types of therapy, and various types of medical cost. First, the results of the relationship between the variables and the PMC revealed that the patients with better QOL, especially those with better social category QOL, tended to have a lower PMC. However, no other variable had any significant associations with the PMC. Second, the results of multiple regression analyses revealed that patients with better QOL, especially those with better social category QOL, in the elderly, and/or those with higher level of education tended to show a lower PMC. In conclusion, the results of the present study suggest that, when we consider evaluating the cost of cancer treatment for postsurgical breast cancer patients, we should take into account the patients' QOL, age, and their level of education.

Journal Article↗

Relationship between metabolic rate, free radicals, differentiation and aging: a unified theory.

Metabolic rate is a major factor governing the rate of aging in both homeotherms and poikilotherms and is inversely related to life span. Homeotherms exhibit stable basal metabolic rates and species-specific life spans. Conversely, in poikilotherms, both basal metabolic rate and life span vary greatly. Metabolic potential (total energy consumed/g/life span) is a species-specific characteristic in Homoetherms and poikilotherms. Length of life is dependent upon the rate at which this fixed metabolic potential is expended, that is, metabolic rate. Oxygen-free radicals produced by metabolism can cause molecular damage. Accumulation of lipofuscin granules, Schiff-base-like, fluorescent material and thiobarbituric acid-reactants, as well as increased exhalation of pentane with age are indicative of free, radical-induced molecular damage. Metabolic rate influences the rate of age-related changes. There is an overlapping compensatory balance between various components of the antioxidant defense system. The total antioxidant capacity of cells tends to decline with age. A dynamic equilibrium may exist between the rate of free radical generation and antioxidant levels. The establishment of this equilibrium is associated with differentiation. It is hypothesized that loss of the equilibrium between free radical generation and antioxidant defenses results in dysdifferentiation, aging and cancer.

Aging↗

[Surgical treatment of far-advanced gastric cancer].

Surgical treatment of far-advanced gastric cancer should be categorized as part of a multidisciplinary treatment. Its therapeutic principles may be summarized as follows: survival should be expected; operative death must be avoided; any operation promoting the growth of cancer should be avoided; oral intake should be made possible, pain should be eased; and the main focus must be removed as far as possible. In the cases with positive peritoneal dissemination, even at P3, a significant extension of life is recognized in the palliative gastrectomy group as compared with the non-resected group. However, considering the postoperative length of life, palliative gastrectomy seems applicable to cases of P1, H1, partly to H2, n3(+), and S3, but in more advanced cases, it was learned essential to determine the surgical method in consideration of the nature of the cancer in the individual cases.

Humans↗