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Modification of cell growth and longevity using an in vivo assay in Drosophila melanogaster.

Beadex is a mutation in Drosophila melanogaster that causes premature cell death in the growing wing blade. The extent of cell loss can be modified by environmental conditions and by other genes. By strictly controlling the genotype, therefore, we can use phenotypic variation in the amount of cell death as an in vivo screen of the action that selected drugs have upon cell longevity and replacement in the growing wing. We found that drugs that modify membrane stability or lysosome activity often, but not always, had similar effects upon cell and organism longevity. Thus, the processes important to cell stability in a growing organ are partially separable from those acting upon the organism as a whole. Furthermore, Minute mutations that reduce the efficiency of protein synthesis and extend developmental time allow Beadex -related cell death to be compensated for by additional cell replacement or increased cell lifespan. Both time-span of developmental activity and the stability of cell membranes and organelles are therefore important variables affecting the makeup of the cell populations in an adult organ.

Acetamides↗

The longevity of international rugby players.

The longevity of New Zealand international rugby players (All Blacks) is compared with the New Zealand male population to test the hypothesis that vigorous leisure time physical activity in the form of rugby in early adulthood is associated with an increased longevity. Data on 822 All Blacks since 1884 are compared with information from New Zealand life tables for males. The life expectancy of All Blacks is the same as the general population although non-Maori All Blacks live almost ten years longer than Maori All Blacks.

Adolescent↗

[Interrelation of familial longevity and the state of the locomotor apparatus].

Relationship was studied between the familial longevity and age changes in the locomotor apparatus. According to the cross-sectional and longitudinal data, the individuals aged over 60 showed a decrease in the factor of familial longevity with pathology of the locomotor apparatus. Changes in clinical and objective data with age appeared to be more pronounced in persons whose families had no long-living relatives. The above changes were more expressed in men.

Aged↗

Growth, kidney disease, and longevity of Syrian hamsters (Mesocricetus auratus) fed varying levels of protein.

Male and female hamsters were fed natural ingredient diets containing 6, 12, 18, or 24% protein. Differences in growth rate, feed consumption, kidney weight, serum chemistry (total protein, serum creatinine, blood urea nitrogen), and longevity were analyzed. The kidneys were examined microscopically and graded according to the severity of nephritis. The 6% protein diet resulted in the lowest frequency of nephritis, but the animals were significantly smaller and had shorter life spans than the remaining groups. The 12% protein diet initially promoted slower growth than 18 or 24% protein, but the differences in body weight eventually became insignificant. The 12% protein diet resulted in a higher frequency of nephritis than 6% protein, but lower than 18 or 24% protein. The 18 and 24% protein diets promoted the most rapid early growth as well as the highest frequency and most severe kidney lesions. Uremia did not appear to be a major cause of death. Longevity did not differ significantly among hamsters of either sex fed 12, 18, or 24% protein diets.

Animals↗

Exercise intensity and longevity in men. The Harvard Alumni Health Study.

OBJECTIVE: To examine the independent associations of vigorous (> or = 6 resting metabolic rate [MET] score) and nonvigorous (< 6 MET score) physical activity with longevity. DESIGN: Prospective cohort study, following up men from 1962 or 1966 through 1988. SETTING/PARTICIPANTS: Subjects were Harvard University alumni, without self-reported, physician-diagnosed cardiovascular disease, cancer, or chronic obstructive pulmonary disease (n = 17,321). Men with a mean age of 46 years reported their physical activities on questionnaires at baseline. MAIN OUTCOME MEASURE: All-cause mortality (3728 deaths). RESULTS: Total energy expenditure and energy expenditure from vigorous activities, but not energy expenditure from nonvigorous activities, related inversely to mortality. After adjustment for potential confounders, the relative risks of dying associated with increasing quintiles of total energy expenditure were 1.00 (referent), 0.94, 0.95, 0.91 and 0.91, respectively (P [trend] < .05). The relative risks of dying associated with less than 630, 630 to less than 1680, 1680 to less than 3150, 3150 to less than 6300, and 6300 or more kJ/wk expended on vigorous activities were 1.00 (referent), 0.88, 0.92, 0.87, and 0.87, respectively (P [trend] = .007). Corresponding relative risks for energy expended on nonvigorous activities were 1.00 (referent), 0.89, 1.00, 0.98, and 0.92, respectively (P [trend] = .36). Analyses of vigorous and nonvigorous activities were mutually adjusted. Among men who reported only vigorous activities (259 deaths), we observed decreasing age-standardized mortality rates with increasing activity (P = .05); among men who reported only nonvigorous activities (380 deaths), no trend was apparent (P = .99). CONCLUSIONS: These data demonstrate a graded inverse relationship between total physical activity and mortality. Furthermore, vigorous activities but not nonvigorous activities were associated with longevity. These findings pertain only to all-cause mortality; nonvigorous exercise has been shown to benefit other aspects of health.

Adult↗

How frailty models can be used for evaluating longevity limits: taking advantage of an interdisciplinary approach.

In this paper we discuss an approach to the analysis of mortality and longevity limits when survival data on related individuals with and without observed covariates are available. The approach combines the ideas of demography and survival analysis with methods of quantitative genetics and genetic epidemiology. It allows us to analyze the genetic structure of frailty in the Cox-type hazard model with random effects. We demonstrate the implementation of this strategy to survival data on Danish twins. We then evaluate the resulting lower bounds for biological limits of human longevity. Finally, we discuss the limitations of this approach and directions of further research.

Aged↗

[Longevity as a developmental process: life history and individual perspectives].

Longevity research often portrays the image that single characteristics of the past life explain best why some people survive into the second century of their lives, and others not. This paper challenges this approach by arguing that longevity should be seen as a life-long development process that still continues in the present lives of the oldest old. Four specific themes are addressed: First, individual differences can increase or decrease with age, depending on the domain studied. Second, historical events have shaped the individual biography of the oldest old and still have a profound impact on the personality and mental health of this age group. Third, individual events such as the loss of family members and friends are powerful recent experiences that challenge the oldest old to adapt to these recent changes in their lives. Finally, the oldest old seem to have unique time perspectives, realizing that remaining life expectancy is short and that time itself may not be of much importance to their current lives.

Aged↗

[Genetics of longevity].

It is possible to use different studies to demonstrate the genetic component of a phenotype. From the beginning of the century, many authors have studied the possible genetic transmission of longevity. The study of genealogies of ascendants first, and then of descendants of elderly individuals shows that the age at death incorrelated in people belonging to the same family. Finally, the studies carried out on monozygot and dizygot twins have made it possible to estimate that this genetic component accounts for approximately 10% of the individual's lifespan. Research on congenic mice which differ only by the chromosomic region of the Major Histocompatibility Complex (MHC) implies that this particular region might have an effect on longevity. However, the study of several alleles of the MHC indicates a complex sex-dependent influence. Several other chromosomic regions are also implied. As far as human beings are concerned, several research teams have worked on the HLA region. Once again, the situation is still far from clear.

Alleles↗

Factors affecting longevity.

In view of the fact that hypercholesterolemia occurs in 31.4%, hypertension in 16.7% and the smoking rate is 58.8% in males (Table 8), risk factors are not low. Despite this, we Japanese preserve a leading position regarding longevity. I hope that I have provided some evidence supporting the proposal that apparently not only a low fat intake but other factors including genetic make up and a relatively high antioxidant intake contribute to our longevity.

Antioxidants↗

Unexpected association between reproductive longevity and blood magnesium levels in a new model of selected mouse strains.

Two recently described mouse strains, with high (MGH) and low (MGL) blood magnesium (Mg) levels were obtained by selection over 19 generations. Both strains exhibit strong differences for characteristics generally known to be related to blood Mg levels, such as increased stress sensitivity and stress-induced aggressivity in MGL mice. In contrast, while experimental Mg deficiency due to low oral Mg intake has been shown to shorten life span and lower reproductive ability, reproductive longevity was longer in the MGL than in the MGH strain. Interestingly, the life spans of the two strains are very similar. Although this character could have been fixed in the strains by chance, with no relationship to the blood Mg level, the possibility of a causal link with the selection cannot be ruled out and is discussed. Regardless of the mechanisms at stake, the MGH and MGL strains appear to constitute a new model for the study of the relationships between reproductive longevity and blood Mg levels.

Aging↗

[Allozyme heterozygosity, sexual maturation rate, and longevity].

Humans, animals, and plants are shown to have a universal polygenic system maintained by stabilizing selection, which underlies highly significant correlations between multilocus allozyme heterozygosity, the sexual maturation rate, and longevity. For 77 animal and 30 plant species, it was demonstrated that allozyme genomic heterozygosity (1) is positively correlated with rate of sexual maturity (2) (r12 = 0.815, P < 0.001) and negatively correlated with longevity; (3) (r13 = -0.793, P < 0.001). These relationships are significantly affected by the genotype-environment interactions that modify the structure of the metabolism related to growth and development. An increase in the number of heterotic genes involved in growth and development increases the energy expenditure in this ontogenetic period, accelerates the sexual maturation rate, and shortens the life span.

Animals↗

Banner year for U.S. longevity.

In 1997 life expectancy for all persons combined rose to a new record high of 76.4 years. Additionally, average future lifetime for newborn girls and boys also established new peaks--79.3 years and 73.4 years, respectively. For girls the 1997 value surpassed the previous high of 79.1 years recorded in 1992 and 1996 while for boys new peaks have been consecutively recorded since 1994. Last year's longevity enhancements among men were larger than those for women--continuing the trend of the past few years. Newborn girls could still anticipate living 5.9 years longer than boys--the gap was 6.0 years in 1996 and 7.0 years in 1989-91. Current projections indicate that the disparity between the genders in average future lifetime may decline to 4.6 years by the year 2050. Also worthy of note is the apparent narrowing of the gap in longevity by race. In 1996 newborn white boys could expect to outlive nonwhite newborn boys by 5.0 years compared with 5.7 years in 1989-91; among girls the disparity diminished from 4.1 years in 1989-91 to 3.6 years in 1996.

Adult↗

Influence of caloric restriction on motor behavior, longevity, and brain lipid composition in Sandhoff disease mice.

Caloric restriction (CR), which improves health and increases longevity, was studied as a therapy in a hexosaminidase beta knockout mouse model of Sandhoff disease (SD), an incurable neurodegenerative disease involving accumulation of brain ganglioside GM2 and asialo-GM2 (GA2). Adult mice were fed a rodent chow diet either ad libitum (AL) or restricted to reduce body weight by 15-18% (CR). Although GM2 and GA2 were elevated, no significant differences were seen between the Hexb-/- and the Hexb+/- mice for most brain phospholipids and cholesterol. Cerebrosides and sulfatides were reduced in the Hexb-/- mice. In addition, rotorod performance was significantly worse in the Hexb-/- mice than in the Hexb+/- mice. CR, which decreased circulating glucose and elevated ketone bodies, significantly improved rotorod performance and extended longevity in the Hexb-/- mice but had no significant effect on brain lipid composition or on cytoplasmic neuronal vacuoles. The expression of CD68 and F4/80 was significantly less in the CR-fed than in the AL-fed Hexb-/- mice. We suggest that the CR delays disease progression in SD and possibly in other ganglioside storage diseases through anti-inflammatory mechanisms.

3-Hydroxybutyric Acid↗

Cloning, sequencing, and transgenic expression of Podospora curvicolla and Sordaria macrospora eEF1A genes: relationship between cytosolic translation and longevity in filamentous fungi.

We have cloned and sequenced the gene encoding the translation elongation factor eEF1A from two filamentous fungi, Podospora curvicolla and Sordaria macrospora. These fungi are close relatives of Podospora anserina and also show senescence syndromes. Comparison of the sequences of the deduced proteins with that of P. anserina reveals that the three proteins differ in several positions. Replacement of the P. anserina gene by either of the two exogenous genes does not entail any modification in P. anserina physiology; the longevity of the fungus is not affected. No alteration of in vivo translational accuracy was detected; however, the exogenous proteins nonetheless promoted a modification of the resistance to the aminoglycoside antibiotic paromomycin. These data suggest that optimization of life span between these closely related fungi has likely not been performed during evolution through modifications of eEF1A activity, despite the fact that mutations in this factor can drastically affect longevity.

Amino Acid Sequence↗

Induction of longevity by cytoplasmic transfer of a linear plasmid in Podospora anserina.

In Podospora anserina the longevity inducing linear plasmid pAL2-1 was transferred from the extrachromosomal long-lived mutant AL2 to the short-lived wild-type strain A. The resulting strain, AL2-IV, exhibited the long-lived phenotype. In the short-lived progeny of crosses between this strain and wild-type strain A, the plasmid was absent. In contrast, all long-lived progeny contained both the autonomous plasmid as well as copies of it integrated in the mitochondrial DNA (mtDNA). Molecular analysis revealed that the integrated plasmid copies most likely resulted from a de novo integration of the autonomous element and the generation of AT-linker sequences at the integration site. We conclude that once the plasmid is present in mitochondria of a particular genetic background, it is able to integrate into the mtDNA and to induce longevity.

Ascomycota↗

Conventional coagulation and thromboelastograph parameters and longevity of continuous renal replacement circuits.

OBJECTIVE: To determine the relationship between conventional and thromboelastograph (TEG) coagulation parameters and continuous renal replacement therapy (CRRT) circuit longevity. DESIGN: Conventional coagulation and TEG parameters were measured at the commencement of and during CRRT. Time to circuit cessation was measured and only circuits reaching a predetermined rise from baseline in the pressure gradient across the haemofilter were diagnosed as failing due to clotting. All other circuits were excluded from analysis. SETTING: A general critical care unit of a metropolitan tertiary hospital. PATIENTS AND PARTICIPANTS: Fourteen consecutive patients requiring CRRT were studied. The CRRT technique used was continuous veno-venous haemodialysis. INTERVENTIONS: Thromboelastograph measurements were made prior to the commencement of CRRT and daily thereafter for each circuit. The international normalised ratio (INR), activated partial thromboplastin time (APTT) and platelet numbers were measured at commencement and 8 hourly thereafter. Heparin was used for anticoagulation unless considered contraindicated. MEASUREMENTS AND RESULTS: Forty-seven circuits with a mean (SD) circuit life of 33.0 (30.2) h were entered. Twenty-five circuits fulfilled circuit clotting criteria; the mean circuit life was 30.8 (22.1) h. Heparin anticoagulation was found to prolong circuit life significantly despite adequate mean circuit life, 33.2 (35.7) h, in heparin-free circuits. The starting APTT and the TEG variables reaction time (R) and coagulation time (RK) were significantly correlated. The starting APTT, starting RK and mean time taken for the amplitude to increase from 2 to 20 mm (K) were predictive of circuit life. None of these variables predicted which patients would need heparin. CONCLUSION: While TEG variables more closely predicted circuit longevity than conventional coagulation variables, the clinical benefit of TEG monitoring of anticoagulation for CRRT would appear to be minimal.

Acute Kidney Injury↗

[Everlasting solidarity? Longevity and generational relations].

Demographic development of industrial societies is determined by continuous low birth rates and increasing life expectancy. The dramatic change in generational structure will be an enormous challenge not only for the public social security systems; as an original place of inter-generational relations, family is particularly faced with increasing life expectancy and the chances and risks of longevity. Need for nursing care is such a risk of longevity, realizing that only about 3% aged between 60 and 80 are in need of care, but about 25% at the age of 80 or older. The majority of nursing cases is well-cared at home, mostly by relatives. Although one might care for relatives for many reasons--not only for love and altruism--empirical data insist on indicating strong family ties based on senses of solidarity and commitment. The focal point of the following article is a case review describing highly emotional family relationships in a home care situation. On the one hand, the description clarifies family solidarity representing the basis of German long-term care insurance since 1995; on the other hand it demonstrates the enormous burden caring for an old mother or father. Increasing life expectancy might even intensify burdens, so that fewer and fewer relatives might be able or willing to accept them. In this matter, new mixtures of private and public services will attain increasing importance. Considering German long-term care insurance a pioneer, it expresses a new sense of limited public responsibility assuming the existence of sufficiently strong family ties.

Aged↗

Long-term clinical performance and longevity of gold alloy vs ceramic partial crowns.

Cast gold partial crowns (CGPC) are an accepted means of restoring posterior teeth. For aesthetic reasons, gold alloys are being increasingly substituted with ceramics. The aim of the present study was to investigate retrospectively the long-term clinical performance and survival of CGPC and compare the results to the ones already reported for ceramic partial crowns (CPC). The CGPC group consisted of 42 patients (24 male, 18 female) randomly sampled from a total of 106 patients with CGPC, with one restoration per patient. The CPC group consisted of 22 patients with a total of 42 restorations. Both types of restoration were done by one experienced dentist. Another two experienced dentists who were not involved in performing the restorations rated both kinds of partial crowns using the modified United State Public Health Service (USPHS) criteria [14]. The Median age of the CGPC was 57 months (range 3-157) and of the CPC and 63 months (range 24-72). Forty-one (98%) of the CGPC and 27 (64%) of the CPC were placed in molars, the rest in premolars. In each group, 40 (95%) restorations were still functioning without any necessity of replacement. Two teeth with CGPC, in situ for 4.5 and 11 years, respectively, had been extracted for periodontal reasons. Two CPC fractured and had to be replaced after 2 and 6.5 years in situ. The USPHS criteria results were similarly good for the gold and ceramic groups. Kaplan-Meier analysis revealed survival probabilities of 72+/-21% and 96+/-4% after 13 and 7 years, respectively, for the CGPC. Survival of the CPC was 81+/-15% after 7 years. No statistically significant difference among survival functions of CGPC and CPC was found. From this data, it can be concluded that the longevity of CPC is not inferior to that of gold alloys. However, more long-term studies comparing the clinical performance and longevity of these two types of indirect restoration in the posterior region with larger numbers of restorations are desirable.

Bicuspid↗