New England Centenarian study

(Last Update: Jul 8)

This project has a new paper in Science. It's a strange and fascinating achievement that a test purports to guess whether you'll live to be 100 with 77% accuracy.

Becoming a centenarian is rare, and guessing the occurrence of rare events is notoriously difficult. It will be interesting to see how these results generalize to a different study population.

UPDATE (Jul 8):

Well, as I mentioned above, guessing the occurrence of rare events is notoriously difficult, and scientists that have looked at this study cast doubt on its validity. If it's too good to be true, it probably ain't. The more interesting question: how did it slip into Science?

Science DOI: 10.1126/science.1190532

Genetic Signatures of Exceptional Longevity in Humans

Paola Sebastiani

Abstract

Healthy aging is thought to reflect the combined influence of environmental factors (lifestyle choices) and genetic factors. To explore the genetic contribution, we undertook a genome-wide association study of exceptional longevity (EL) in 1055 centenarians and 1267 controls. Using these data, we built a genetic model that includes 150 single-nucleotide polymorphisms (SNPs) and found that it could predict EL with 77% accuracy in an independent set of centenarians and controls. Further in silico analysis revealed that 90% of centenarians can be grouped into 19 clusters characterized by different combinations of SNP genotypes—or genetic signatures—of varying predictive value. The different signatures, which attest to the genetic complexity of EL, correlated with differences in the prevalence and age of onset of age-associated diseases (e.g., dementia, hypertension, and cardiovascular disease) and may help dissect this complex phenotype into subphenotypes of healthy aging.

Link

Children of centenarians: extraverted and not neurotic

Journal of the American Geriatrics Society doi:

Personality Traits of Centenarians' Offspring

Jane L. Givens et al.

Abstract

OBJECTIVES: To determine whether the offspring of centenarians have personality characteristics that are distinct from the general population.

DESIGN: Case-control.

SETTING: Nationwide U.S. sample.

PARTICIPANTS: Unrelated offspring of centenarians (n=246, mean age 75) were compared with published norms.

MEASUREMENTS: Using the NEO-Five-Factor Inventory (NEO-FFI) questionnaire, measures of the personality traits neuroticism, extraversion, openness, agreeableness, and conscientiousness were obtained. T-scores and percentiles were calculated according to sex and used to interpret the results.

RESULTS: Male and female offspring of centenarians scored in the low range of published norms for neuroticism and in the high range for extraversion. The women also scored comparatively high in agreeableness. Otherwise, both sexes scored within normal range for conscientiousness and openness, and the men scored within normal range for agreeableness.

CONCLUSION: Specific personality traits may be important to the relative successful aging demonstrated by the offspring of centenarians. Similarities across four of the five domains between male and female offspring is noteworthy and may relate to their successful aging. Measures of personality are an important phenotype to include in studies that assess genetic and environmental influences of longevity and successful aging.

Link

mtDNA of Tunisian centenarians

Mech Ageing Dev. 2008 Dec 24.

Data from complete mtDNA sequencing of Tunisian centenarians: Testing haplogroup association and the "golden mean" to longevity.

Costa MD, Cherni L, Fernandes V, Freitas F, Ammar El Gaaied AB, Pereira L.

Since the mitochondrial theory of ageing was proposed, mitochondrial DNA (mtDNA) diversity has been largely studied in old people, however complete genomes are still rare, being limited to Japanese and UK/US samples. In this work, we evaluated possible longevity associated polymorphisms/haplogroups in an African population, from Tunisia, by performing complete mtDNA sequencing. This population has a mixed Eurasian/sub-Saharan mtDNA gene pool, which could potentially facilitate the evaluation of association for sub-Saharan lineages. Sub-Saharan haplogroups were shown to be significantly less represented in centenarians (9.5%) than in controls (54.5%), but it is not possible to rule out an influence of population structure, which is high in these populations. No recurrent polymorphism were more frequent in centenarians than in controls, and although the Tunisian centenarians presented less synonymous and replacement polymorphisms than controls, this difference was not statistically significant. So far, it does not seem that centenarians have significantly less mildly deleterious substitutions, not only in Tunisia but also in Japanese and UK/US samples, as tested here, not favouring a "golden mean" to longevity.

Link

mtDNA haplogroup J not associated with Ashkenazi Jewish centenarians

Table 1 has haplogroup frequencies in Ashkenazi centenarians and controls, and Table 2 from Ashkenazi Jews of various origins.

PLoS ONE doi: 10.1371/journal.pone.0003425

Ashkenazi Jewish Centenarians Do Not Demonstrate Enrichment in Mitochondrial Haplogroup J

Liran I. Shlush et al.

Abstract

Background

Association of mitochondrial haplogroup J with longevity has been reported in several population subgroups. While studies from northern Italy and Finland, have described a higher frequency of haplogroup J among centenarians in comparison to non-centenarian, several other studies could not replicate these results and suggested various explanations for the discrepancy.

Methodology/Principal Findings

We have evaluated haplogroup frequencies among Ashkenazi Jewish centenarians using two different sets of matched controls. No difference was observed in the haplogroup J frequencies between the centenarians or either matched control group, despite adequate statistical power to detect such a difference. Furthermore, the lack of association was robust to population substructure in the Ashkenazi Jewish population. Given this discrepancy with the previous reported associations in the northern Italian and the Finnish populations, we conducted re-analysis of these previously published data, which supported one of several possible explanations: i) inadequate matching of cases and controls; ii) inadequate adjustment for multiple comparison testing; iii) cryptic population stratification.

Conclusions/Significance

There does not exist a universal association of mitochondrial haplogroup J with longevity across all population groups. Reported associations in specialized populations may reflect genetic or other interactions specific to those populations or else cryptic confounding influences, such as inadequate matching attributable to population substructure, which are of general relevance to all studies of the possible association of mitochondrial DNA haplogroups with common complex phenotypes.

Link

Health status of Greek centenarians

Arch Gerontol Geriatr. 2007 May 16; [Epub ahead of print]

Assessment of the health status of Greek centenarians.

Darviri C, Demakakos P, Charizani F, Tigani X, Tsiou C, Chalamandaris AG, Tsagkari C, Chliaoutakis J.

The present study aims at describing the health status of a sample of relatively functional and healthy Greek centenarians and at exploring the potential gender differences in health in this sample. Its objectives are to add to the accumulation of knowledge about the health status of centenarians and therefore to contribute to the exploration of the mechanisms of healthy longevity. The study employs a non-representative community sample of Greek centenarians of both sexes (N=47). It uses descriptive statistics in order to outline the health status of the participants and non-parametric tests to assess the statistical significance of the observed sex-differences. The study shows that the centenarians of our sample are relatively healthy and functional (15% of the sample was free of any major chronic disease). It also suggests, that the sex-difference in survival is statistical significant (p less or equal 0.013), and that the morbidity and co-morbidity rates of the Greek centenarians are relatively low (mean value of co-morbidity=1.4+/-0.97, S.D.). Moreover, it provides valuable information on the anthropometric characteristics of the sample, and on health services utilization. These results indicate that exceptional longevity is not necessarily accompanied by disability, disease and total dependence on others.

Link

Long Life and Good Mental Function Gene Identified

Single Gene Could Lead to Long Life, Better Mental Function

Barzilai and his colleagues examined 158 people of Ashkenazi, or Eastern European Jewish, descent who were 95 years of age or older. They chose Ashkenazi Jews since current generations stem from a relatively limited number of ancestors. This means they have a comparatively uniform genetic makeup, making it easier to identify important genetic differences.

The scientists gave these volunteers a common test of mental function, consisting of 30 questions. Correctly answering 25 of the questions meant a subject passed the test. Those centenarians who passed were two to three times more likely to have a common variant of a particular gene, called the CETP gene, than those who did not. When the researchers studied another 124 Ashkenazi Jews between 75 and 85 years of age, those subjects who passed the test of mental function were five times more likely to have this gene variant than their counterparts.