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PLoS ONE. 2008 Jun 11;3(6):e2421.

Mitochondrial DNA Haplogroup D4a Is a Marker for Extreme Longevity in Japan
Erhan Bilal1, Raul Rabadan2, Gabriela Alexe3, Noriyuki Fuku4, Hitomi Ueno4, Yutaka Nishigaki4, Yasunori Fujita5, Masafumi Ito5, Yasumichi Arai6, Nobuyoshi Hirose6, Andrei Ruckenstein7, Gyan Bhanot1,2,8, Masashi Tanaka4*

1 BioMaPS Institute, Rutgers University, Piscataway, New Jersey, United States of America2 Simons Center for Systems Biology, Institute for Advanced Study, Princeton, New Jersey, United States of America3 Computational Biology and Bioinformatics, The Broad Institute of MIT and Harvard, Cambridge, Massachusetts, United States of America4 Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Itabashi-ku, Tokyo, Japan5 Department of Longevity and Aging Research, Gifu International Institute of Biotechnology, Kakamigahara, Gifu, Japan6 Department of Geriatric Medicine, Keio University School of Medicine, Shinjuku-ku, Tokyo, Japan7 Department of Physics, Boston University, Boston, Massachusetts, United States of America8 Department of Biomedical Engineering, Rutgers University, Piscataway, New Jersey, United States of America


Abstract

We report results from the analysis of complete mitochondrial DNA (mtDNA) sequences from 112 Japanese semi-supercentenarians (aged above 105 years) combined with previously published data from 96 patients in each of three non-disease phenotypes: centenarians (99–105 years of age), healthy non-obese males, obese young males and four disease phenotypes, diabetics with and without angiopathy, and Alzheimer's and Parkinson's disease patients. We analyze the correlation between mitochondrial polymorphisms and the longevity phenotype using two different methods. We first use an exhaustive algorithm to identify all maximal patterns of polymorphisms shared by at least five individuals and define a significance score for enrichment of the patterns in each phenotype relative to healthy normals. Our study confirms the correlations observed in a previous study showing enrichment of a hierarchy of haplogroups in the D clade for longevity. For the extreme longevity phenotype we see a single statistically significant signal: a progressive enrichment of certain “beneficial” patterns in centenarians and semi-supercentenarians in the D4a haplogroup. We then use Principal Component Spectral Analysis of the SNP-SNP Covariance Matrix to compare the measured eigenvalues to a Null distribution of eigenvalues on Gaussian datasets to determine whether the correlations in the data (due to longevity) arises from some property of the mutations themselves or whether they are due to population structure. The conclusion is that the correlations are entirely due to population structure (phylogenetic tree). We find no signal for a functional mtDNA SNP correlated with longevity. The fact that the correlations are from the population structure suggests that hitch-hiking on autosomal events is a possible explanation for the observed correlations.

J Immunol. 2008 Jul 1;181(1):109-15.



An Age-Old Paradigm Challenged: Old Baboons Generate Vigorous Humoral Immune Responses to LcrV, A Plague Antigen.

Stacy S, Pasquali A, Sexton VL, Cantwell AM, Kraig E, Dube PH.

Department of Cellular and Structural Biology.

Immune senescence in the elderly results in decreased immunity with a concomitant increase in susceptibility to infection and diminished efficacy of vaccination. Nonhuman primate models have proven critical for testing of vaccines and therapeutics in the general population, but a model using old animals has not been established. Toward that end, immunity to LcrV, a protective Ag from Yersinia pestis, was tested in young and old baboons. Surprisingly, there was no age-associated loss in immune competence; LcrV elicited high-titer, protective Ab responses in the older individuals. The primary responses in the younger baboons were lower, but they did show boosting upon secondary immunization to the levels achieved in the old animals. The LcrV Ag was also tested in mice and, as expected, age-associated loss of immunity was seen; older animals responded with lower-titer Abs and, as a result, were more susceptible to Yersinia challenge. Thus, although age-related loss in immune function has been observed in humans, rodents, and some nonhuman primates, baboons appear to be unusual; they age without losing immune competence.

Bull a écrit :Une étude, pour l'instant préliminaire, semble pointer un fond génétique à la très longue longévité chez les Humains.

Eons a écrit :N'avez-vous pas remarqué que les centenaires sont quasi exclusivement des gens entourés d'une famille aimante et/ou d'amis – même quand il n'y a pas d'héritage à la clef – ?

Lensman a écrit :Claude Lévi-Strauss fête ses 100 ans cette année.
Oncle Joe

Charlotte a écrit :

Lensman a écrit :Claude Lévi-Strauss fête ses 100 ans cette année.
Oncle Joe

Et d'après ce que j'en ai entendu dire, il est encore très impressionnant : trois heures de conférences sans notes !