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PubMed2005

Longevity following the experience of parental divorce.

An archival prospective design was used to study mediating and moderating variables for the association between parental divorce and increased mortality risk, using a sub-group (n = 1183) of individuals from the US Terman Life Cycle Study covering the period 1921-2000. In childhood, both socioeconomic status (SES) and family psychosocial environment were related to parental divorce but did little to explain its effects. The higher mortality risk associated with experiencing parental divorce was ameliorated among individuals (especially men) who achieved a sense of personal satisfaction by mid-life. Behaviorally, smoking was the strongest mediator of the divorce-mortality link. This study extends previous work on the long-term effects of parental divorce and reveals some reasons why the stress of parental divorce in childhood need not necessarily lead to negative later-life outcomes.

Child↗
PubMed2006

Cancer screening in older adults in an era of genomics and longevity.

OBJECTIVES: To provide an overview of cancer genomics and cancer screening in older adults with a focus on breast, prostate, and colon cancers. DATA SOURCES: Journal articles, research articles, and web sites. CONCLUSION: Cancer screening in older populations is often in the context of one or more co-morbid conditions, cancer survivorship, genomic information, and competing health priorities. The field of cancer screening has outgrown the tools available to enable health care providers and older adults to make informed cancer screening decisions. Research is needed to develop clinical screening tools that integrate age, cancer risk, life expectancy, and comorbidity. IMPLICATIONS FOR NURSING PRACTICE: Health care providers are faced with opportunities and challenges in the prevention and early detection of cancer in older Americans.

Aged↗
PubMed2006

The co-evolution of intergenerational transfers and longevity: an optimal life history approach.

How would resources be allocated among fertility, survival, and growth in an optimal life history? The budget constraint assumed by past treatments limits the energy used by each individual at each instant to what it produces at that instant. We consider under what conditions energy transfers from adults, which relax the rigid constraint by permitting energetic dependency and faster growth for the offspring, would be advantageous. In a sense, such transfers permit borrowing and lending across the life history. Higher survival and greater efficiency in energy production at older ages than younger both favor the evolution of transfers. We show that if such transfers are advantageous, then increased survival up to the age of making the transfers must co-evolve with the transfers themselves.

Animals↗
PubMed2003

Complementation of Escherichia coli ubiF mutation by Caenorhabditis elegans CLK-1, a product of the longevity gene of the nematode worm.

Caenorhabditis elegans CLK-1 was identified from long-lived mutant worms, and is believed to be involved in ubiquinone biosynthesis. The protein belongs to the eukaryotic CLK-1/Coq7p family, which is also similar to the bacterial Coq7 family, that hydroxylates demethoxyubiquinone, resulting in the formation of hydroxyubiquinone, a precursor of ubiquinone. In Escherichia coli, the corresponding reaction is catalyzed by UbiF, a member of a distinct class of hydroxylase. Although previous studies suggested that the eukaryotic CLK-1/Coq7 family is a hydroxylase of demethoxyubiquinone, there was no direct evidence to show the enzymatic activity of the eukaryotic CLK-1/Coq7 family. Here we show that the plasmid encoding C. elegans CLK-1 supported aerobic respiration on a non-fermentable carbon source of E. coli ubiF mutant strain and rescued the ability to synthesize ubiquinone, suggesting that the eukaryotic CLK-1/Coq7p family could function as bacterial UbiF.

Animals↗
PubMed1998

Longevity of lobsters is linked to ubiquitous telomerase expression.

Mammals have high growth rates in embryonic and juvenile phases and no growth in adult and senescent phases. We analyzed telomerase activity in a fundamentally different animal which grows indeterminately. Lobsters (Homarus americanus) grow throughout their life and the occurrence of senescence is slow. A modified TRAP assay was developed and the lobster telomeric repeat sequence TTAGG was determined. We detected telomerase activities which were dependent on RNA and protein components, required dGTP, dATP and dTTP, but not dCTP. Telomerase products with a five nucleotide periodicity were generated. High telomerase activities were detected in all lobster organs. We conclude that telomerase activation is a conserved mechanism for maintaining long-term cell proliferation capacity and preventing senescence, not only in cellular models or embryonic life stages but also in adult multicellular organisms.

Animals↗
PubMed1997

Analysis of the apo E/apo C-I, angiotensin converting enzyme and methylenetetrahydrofolate reductase genes as candidates affecting human longevity.

Genetic factors are likely to affect human survival, since twin studies have shown greater concordance for age of death in monozygotic compared to dizygotic twins. Coronary artery disease is an important contributor to premature mortality in the UK. Accordingly, we have chosen genes associated with cardiovascular risk, apo E/apo C-I, angiotensin converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR), as candidates which may affect longevity/survival into old age. An association study was performed by comparing allele and genotype frequencies at polymorphic loci associated with these genes in 182 women and 100 men aged 84 years and older with 100 boys and 100 girls younger than 17 years. MTHFR allele and genotype frequencies were similar in the elderly and young populations. Apo C-I allele and genotype frequencies were significantly different in the elderly women compared to the younger sample (P < 0.05). No difference was observed in the elderly men. At the neighbouring apo E gene, we only observed a difference between genotypes in the elderly women and the young sample; however, this did not retain significance when the genotype frequencies of the young sample were adjusted to values expected from the allele frequencies on the basis of Hardy-Weinberg equilibrium and compared to observed genotypes in elderly men and women. In contrast to previous studies, apo E2 was not overrepresented in the elderly men or women. Thus, the proposition that apo E2, E3 and E4 protein isoforms are themselves functionally associated with increasing risks for early death, may be too simplistic. The I/I ACE was depleted in the elderly males but not the elderly females. Furthermore, significant differences were observed between ACE genotypes in elderly men and elderly women. These data suggest that the penetrance of loci which influence survival may vary according to sex. The depletion of the ACE I/I genotype in elderly men is generally consistent with a previous study which found decreased frequencies of the I allele in French centenarians compared to younger controls. However, these results are apparently paradoxical, since others have suggested that the I allele is associated with increased cardiovascular risk. Clarification of the overall effect of a genotype on survival will be vital if therapies are to be considered which target specific genetic variants.

Adolescent↗
PubMed1998

A common methylenetetrahydrofolate reductase gene mutation and longevity.

Homozygotes (TT genotype) for the C677T mutation in the gene of methylenetetrahydrofolate reductase (C677T/MTHFR mutation) constitute about 12% of the Caucasian population. They have mild hyperhomocysteinemia which is an established risk factor for cardiovascular disease. If the mutation is associated with premature death its prevalence is expected to be lower in the elderly than in the young. To test this we determined the C677T/MTHFR genotypes in 220 newborn and 222 elderly 80-108-year-old Swedes. In the newborn and elderly, the allele frequency, of the C677T/MTHFR mutation was 29.1 and 27.0% and the mutant homozygote frequency was 10.0 and 9.5%, respectively. In a meta analysis of the present and three previous studies including a total of 1388 elderly and 1415 younger subjects, the odds ratio (OR) representing the likelihood of the TT genotype to attain old age relative to the CC genotype was 0.87 (95% confidence interval (CI), 0.69-1.11) and relative to both the CC and CT genotypes was 0.83 (95% CI, 0.66-1.04). This finding does not suggest that the C677T/MTHFR mutation is a strong risk factor for diseases frequently leading to premature death.

Aged↗
PubMed1998

The effects of an extract of Ginkgo biloba, EGb 761, on cognitive behavior and longevity in the rat.

Extracts of the leaves of the Ginkgo biloba tree are widely used throughout the world for their purportedly beneficial effects on brain function. In the present investigation, a standardized extract, EGb 761, was self-administered orally by male Fischer 344 rats that were then tested in an eight-arm radial maze. The tasks employed were a) continuous learning and b) delayed nonmatching to position. Chronic postsession administration of EGb 761 at a dose of 50 mg/kg had no effect on continuous learning but the same dose given presession resulted in a trend toward fewer sessions to reach criterion performance as well as fewer errors. In addition, it was observed that rats chronically treated with EGb 761 lived significantly longer than vehicle-treated subjects. In a delayed nonmatching to position task using a 30-min delay in 20-month-old rats. EGb 761 administered presession produced a dose-related decrease in total, retroactive, and proactive errors; a repeated-measures design was used, with subjects serving as their own controls. Following the dose-response determination, the group, now 26 months of age, was divided in two with half receiving EGb 761 at a dose of 200 mg/kg presession and the other half vehicle (sweetened condensed milk). A statistically significant positive effect of treatment with EGb-761 was observed. The present data are consistent with the beneficial effects on cognitive performance which have been widely reported in human subjects. In addition, the data suggest that the methods employed, i.e., continuous learning and delayed nonmatching to position tasks in aged rats, are capable of detecting drugs of possible value in the treatment of human cognitive impairment. Finally, the present results encourage a search for the pharmacologically active principles of EGb 761 and for their mechanisms of action.

Animals↗
PubMed2003

HLA haplotypes and TNF polymorphism do not associate with longevity in the Irish.

Polymorphism of the human leukocyte antigen has been implicated in a number of autoimmune disorders including ageing. In the course of the present study, no association of the human leukocyte antigen (HLA)-A1, B8, DR3 haplotype with a male Irish aged population, as previously reported, was observed. Two polymorphic nucleotides in the TNF cluster (G-308A TNF-alpha and G+252A TNF-beta), associated with increased TNF-alpha production, were shown to be in tight linkage disequilibrium with the class I and II HLA loci, generating HLA haplotypes with extended linkage disequilibrium. However, no age-related allele or genotype frequencies were observed for either polymorphic nucleotide.

Adult↗
PubMed2003

Hormone levels and cataract scores as sex-specific, mid-life predictors of longevity in genetically heterogeneous mice.

Serum levels of thyroxine (T4), leptin, and insulin-like growth factor-I (IGF-I), as well as cataract severity, were evaluated as predictors of life span in a population of genetically heterogeneous mice (UM-HET3). Long life span was predicted by low levels of leptin at age 4 months in females, and by low levels of IGF-I at age 15 months and high levels of T4 at age 4 months, in males. Cataract severity at either 18 or 24 months was also a significant predictor of life span in females only, but in contrast to what has been reported in human studies, relatively severe cataract was correlated with longer life span. Additional work is needed to evaluate the role of these hormones as potential modulators of the aging process, and to resolve the conflicting data obtained for cataract severity as a predictor of life span.

Animals↗
PubMed1999

Longevity, stress response, and cancer in aging telomerase-deficient mice.

Telomere maintenance is thought to play a role in signaling cellular senescence; however, a link with organismal aging processes has not been established. The telomerase null mouse provides an opportunity to understand the effects associated with critical telomere shortening at the organismal level. We studied a variety of physiological processes in an aging cohort of mTR-/- mice. Loss of telomere function did not elicit a full spectrum of classical pathophysiological symptoms of aging. However, age-dependent telomere shortening and accompanying genetic instability were associated with shortened life span as well as a reduced capacity to respond to stresses such as wound healing and hematopoietic ablation. In addition, we found an increased incidence of spontaneous malignancies. These findings demonstrate a critical role for telomere length in the overall fitness, reserve, and well being of the aging organism.

Aging↗