Publication Title: 

Lifespan experiments of lower organisms and mammals along with recent studies of centenarians are making inroads into delineating genetic factors that determine the ability to achieve exceptional longevity. These models may be helpful for the discovery of both longevity-enabling genes as well as genes associated with increased propensity to develop specific diseases.

Perls, Thomas
Puca, Annibale
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

Okinawa, an isolated island prefecture of Japan, has among the highest prevalence of exceptionally long-lived individuals in the world; therefore, we hypothesized that, within this population, genes that confer a familial survival advantage might have clustered. We analyzed the pedigrees of 348 centenarian families with 1142 siblings and compared sibling survival with that of the 1890 Okinawan general population cohort. Both male and female centenarian siblings experienced approximately half the mortality of their birth cohort-matched counterparts.

Willcox, Bradley J.
Willcox, D. Craig
He, Qimei
Curb, J. David
Suzuki, Makoto
Publication Title: 
American Journal of Epidemiology

Family studies of exceptional longevity can potentially identify genetic and other factors contributing to long life and healthy aging. Although such studies seek families that are exceptionally long lived, they also need living members who can provide DNA and phenotype information. On the basis of these considerations, the authors developed a metric to rank families for selection into a family study of longevity.

Sebastiani, Paola
Hadley, Evan C.
Province, Michael
Christensen, Kaare
Rossi, Winifred
Perls, Thomas T.
Ash, Arlene S.
Publication Title: 
Age (Dordrecht, Netherlands)

Low handgrip strength has been linked with premature mortality in diverse samples of middle-aged and elderly subjects. The value of handgrip strength as marker of "exceptional" human longevity has not been previously explored. We postulated that the genetic influence on extreme survival might also be involved in the muscular strength determination pathway. Therefore, the objective of this study was to assess the muscle strength in a sample of middle-aged adults who are genetically enriched for exceptional survival and comparing them to a control group.

Ling, Carolina H. Y.
de Craen, Anton J. M.
Slagboom, P. Eline
Westendorp, Rudi G. J.
Maier, Andrea B.
Publication Title: 
Aging Cell

Atrophy is one of the major age-related changes in the brain. The absence of brain atrophy in elderly individuals reflects deceleration in the process of biological aging. Moreover, results from human twin studies suggest a large genetic influence on the variance of human brain tissue volumes. To investigate the association of brain volumes with exceptional longevity, we tested whether middle-aged to elderly offspring of nonagenarian siblings have larger brain volumes than their spouses using magnetic resonance imaging.

Altmann-Schneider, Irmhild
de Craen, Anton J. M.
Slagboom, Pieternella E.
Westendorp, Rudi G. J.
van Buchem, Mark A.
Maier, Andrea B.
van der Grond, Jeroen
Publication Title: 
Aging Cell

Clear evidence exists for heritability of human longevity, and much interest is focused on identifying genes associated with longer lives. To identify such longevity alleles, we performed the largest genome-wide linkage scan thus far reported. Linkage analyses included 2118 nonagenarian Caucasian sibling pairs that have been enrolled in 15 study centers of 11 European countries as part of the Genetics of Healthy Aging (GEHA) project.

Beekman, Marian
BlanchÈ, HÈlËne
Perola, Markus
Hervonen, Anti
Bezrukov, Vladyslav
Sikora, Ewa
Flachsbart, Friederike
Christiansen, Lene
de Craen, Anton J. M.
Kirkwood, Tom B. L.
Rea, Irene Maeve
Poulain, Michel
Robine, Jean-Marie
Valensin, Silvana
Stazi, Maria Antonietta
Passarino, Giuseppe
Deiana, Luca
Gonos, Efstathios S.
Paternoster, Lavinia
S¯rensen, Thorkild I. A.
Tan, Qihua
Helmer, Quinta
van den Akker, Erik B.
Deelen, Joris
Martella, Francesca
Cordell, Heather J.
Ayers, Kristin L.
Vaupel, James W.
Tˆrnwall, Outi
Johnson, Thomas E.
Schreiber, Stefan
Lathrop, Mark
Skytthe, Axel
Westendorp, Rudi G. J.
Christensen, Kaare
Gampe, Jutta
Nebel, Almut
Houwing-Duistermaat, Jeanine J.
Slagboom, Pieternella Eline
Franceschi, Claudio
GEHA consortium
Publication Title: 
Journal of Human Genetics

Bivariate survival models with discretely distributed frailty based on the major gene concept and applied to the data on related individuals such as twins and sibs can be used to estimate the underlying hazard, the relative risk and the frequency of the longevity allele. To determine the position of the longevity gene, additional genetic markers data are needed. If the action of the longevity allele does not depend on its position in the genome, these two problems can be solved separately using a two-step procedure.

Begun, Alexander
Publication Title: 
American Journal of Human Genetics

We previously identified a functional variant of KLOTHO (termed "KL-VS"), which harbors two amino acid substitutions in complete linkage disequilibrium and is associated with reduced human longevity when in homozygosity. Klotho-deficient mice display extensive arteriosclerosis when fed a normal diet, suggesting a potent genetic predisposition.

Arking, Dan E.
Becker, Diane M.
Yanek, Lisa R.
Fallin, Daniele
Judge, Daniel P.
Moy, Taryn F.
Becker, Lewis C.
Dietz, Harry C.
Publication Title: 
CMAJ: Canadian Medical Association journal = journal de l'Association medicale canadienne

BACKGROUND: Low levels of 25(OH) vitamin D are associated with various age-related diseases and mortality, but causality has not been determined. We investigated vitamin D levels in the offspring of nonagenarians who had at least one nonagenarian sibling; these offspring have a lower prevalence of age-related diseases and a higher propensity to reach old age compared with their partners.

Noordam, Raymond
de Craen, Anton J. M.
Pedram, Pardis
Maier, Andrea B.
Mooijaart, Simon P.
van Pelt, Johannes
Feskens, Edith J.
Streppel, Martinette T.
Slagboom, P. Eline
Westendorp, Rudi G. J.
Beekman, Marian
van Heemst, Diana
Publication Title: 
American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics: The Official Publication of the International Society of Psychiatric Genetics

Protocadherin X and Protocadherin Y (PCDHX and PCDHY) are cell-surface adhesion molecules expressed predominantly in the brain. The PCDHX/Y gene-pair was generated by an X-Y translocation approximately 3 million years ago (MYA) that gave rise to the Homo sapiens-specific region of Xq21.3 and Yp11.2 homology. Genes within this region are expected to code for sexually dimorphic human characteristics, including, for example, cerebral asymmetry a dimension of variation that has been suggested is relevant to psychosis.

Giouzeli, Maria
Williams, Nic A.
Lonie, Lorne J.
DeLisi, Lynn E.
Crow, Timothy J.


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