c-Abl is required for development and optimal cell proliferation in the context of p53 deficiency. (65/3329)

The c-Abl tyrosine kinase and the p53 tumor suppressor protein interact functionally and biochemically in cellular genotoxic stress response pathways and are implicated as downstream mediators of ATM (ataxia-telangiectasia mutated). This fact led us to study genetic interactions in vivo between c-Abl and p53 by examining the phenotype of mice and cells deficient in both proteins. c-Abl-null mice show high neonatal mortality and decreased B lymphocytes, whereas p53-null mice are prone to tumor development. Surprisingly, mice doubly deficient in both c-Abl and p53 are not viable, suggesting that c-Abl and p53 together contribute to an essential function required for normal development. Fibroblasts lacking both c-Abl and p53 were similar to fibroblasts deficient in p53 alone, showing loss of the G(1)/S cell-cycle checkpoint and similar clonogenic survival after ionizing radiation. Fibroblasts deficient in both c-Abl and p53 show reduced growth in culture, as manifested by reduction in the rate of proliferation, saturation density, and colony formation, compared with fibroblasts lacking p53 alone. This defect could be restored by reconstitution of c-Abl expression. Taken together, these results indicate that the ATM phenotype cannot be explained solely by loss of c-Abl and p53 and that c-Abl contributes to enhanced proliferation of p53-deficient cells. Inhibition of c-Abl function may be a therapeutic strategy to target p53-deficient cells selectively.  (+info)

The effect of longevity on spending for acute and long-term care. (66/3329)

BACKGROUND: The proportion of the population made up of elderly persons in the United States is projected to increase from 13 percent of the population in 2000 to 20 percent by 2030. The implications for health care expenditures may be profound, because elderly persons use health care services at a greater rate than younger persons. We estimated total expenditures for acute and long-term care from the age of 65 years until death and in the last two years of life. METHODS: We combined data from Medicare, the National Mortality Followback Survey, and the National Medical Expenditure Survey to estimate total national expenditures for health care according to the age at death. We also simulated expenditures with the use of projected demographic characteristics of two cohorts: people turning 65 in 2000 and those turning 65 in 2015. RESULTS: Total expenditures (in 1996 dollars) from the age of 65 years until death increase substantially with longevity, from $31,181 for persons who die at the age of 65 years to more than $200,000 for those who die at the age of 90, in part because of steep increases in nursing home expenditures for very old persons. Spending in the last two years of life also increases with longevity, but a reduction in Medicare expenditures ($37,000 for persons who die at the age of 75 years and $21,000 for those who die at the age of 95) moderates the effect of the increase in nursing home expenditures ($6,000 for those who die at the age of 75 years and $32,000 for those who die at the age of 95). Health care spending for women is consistently higher than that for men, after adjustment for the increased longevity of women. Simulations show that increased longevity after the age of 65 years has a relatively small effect on the anticipated increase in spending, especially for services covered by Medicare, from 2000 to 2015. The effects of the larger number of people born in 1950 than in 1935 and the larger number of people surviving to the age of 65 years are much more important. CONCLUSIONS: In the United States, the effect of longevity on expenditures for acute care differs from its effect on expenditures for long-term care. Acute care expenditures, principally for hospital care and physicians' services, increase at a reduced rate as the age at death increases, whereas expenditures for long-term care increase at an accelerated rate. Increases in longevity after the age of 65 years may result in greater spending for long-term care, but the increase in the number of elderly persons has a more important effect on total spending.  (+info)

Life tables as "predictors" of average longevity. (67/3329)

Selected figures from Canadian life tables have been analysed to illustrate one potential use of routinely collected and published data. A plea is made for the inclusion of the fundamentals of demography in undergraduate medical education.  (+info)

Evidence of sex-linked effects on the inheritance of human longevity: a population-based study in the Valserine valley (French Jura), 18-20th centuries. (68/3329)

A long-standing puzzle in gerontology is the sex dependence of human longevity and its inheritance. We have analysed the sex-linked pattern of inheritance of longevity from 643 nuclear families on the historical population register of a French valley. We have focused on mean conditional life expectancy at a minimum age of 50 years, thus, in the present study, longevity refers to late or post-reproductive survival. A comparison of parents' and offspring's longevity has shown the existence of a heritable component of late survival in this population. We have found that the heritable component was substantially larger for daughters compared to sons. Moreover, this result appeared to be specific to late survival, that is, when only post-reproductive mortality for parental and offspring generations is taken into account. The stronger resemblance of parents to their daughters was no longer observed when considering younger ages at death for the offspring. This observation explains the hitherto unaccountable diversity of data in previous studies.  (+info)

Markers for bone metabolism in a long-lived case of thanatophoric dysplasia. (69/3329)

We report a male patient with type 1 thanatophoric dysplasia, now eight years old, having a mutation in the FGFR3 gene. Radiological examination at birth revealed that the ribs and the bones of the extremities were very short and vertebral bodies were greatly reduced in height with wide intervertebral spaces. The femurs were shaped like French telephone receivers. Because of respiratory insufficiency due to the narrow thorax, the patient has been intubated and supported by continuous mechanical ventilation since the day after birth. Since 5 years of age, despite sufficient caloric intake, his body weight never increased above 4700 g, body height 49.0 cm, head circumference 46.1 cm, and chest circumference 35.8 cm. Acanthosis nigricance and huge bilateral coral-like urolithiases has been present. His mental development was severely retarded but he was able to make emotional expressions. Although developments in motor functions could not be assessed, his neurodevelopmental milestones in social relationships and language perception seemed to be at the level of a 10 to 12 month old. His bone maturation was also severely retarded. All of the assays of his serum and urinary bone formation- or resorption-related substances were within normal limits for age. Therefore, bone formation as well as bone resorption activities seemed normal and not responsible for his growth retardation.  (+info)

Cloning and expression of the sponge longevity gene SDLAGL. (70/3329)

Porifera show a characteristic Bauplan in spite of the fact that (almost) all cells are telomerase-positive and presumably provided with an unlimited potency for cell proliferation. One gene, SDLAGL, was identified in the marine sponge Suberites domuncula whose deduced polypeptide showed high sequence similarity to the longevity assurance genes from other Metazoa. While in single cells no transcripts of SDLAGL could be identified, high expression was seen after re-aggregation of single cells and in proliferating cells of primmorphs.  (+info)

Problems of an aging population in an era of technology. (71/3329)

With the substantially growing number of elderly persons in Canada and the rest of the developed world, the need for adequate health and social care will increase. Health and social service providers must develop policies and programs allowing the elderly to lead rich and independent lives for as long as possible. As advances in age-related diseases are made, the elderly will potentially live longer and lead more active and fulfilling lives. Society, governments and those involved in the care of the elderly must meet the new challenges of this aging population in a humane and respectful way.  (+info)

Extension of life-span with superoxide dismutase/catalase mimetics. (72/3329)

We tested the theory that reactive oxygen species cause aging. We augmented the natural antioxidant systems of Caenorhabditis elegans with small synthetic superoxide dismutase/catalase mimetics. Treatment of wild-type worms increased their mean life-span by a mean of 44 percent, and treatment of prematurely aging worms resulted in normalization of their life-span (a 67 percent increase). It appears that oxidative stress is a major determinant of life-span and that it can be counteracted by pharmacological intervention.  (+info)