Pedigree

Publication Title: 
Current Opinion in Genetics & Development

Once thought to be an extremely complex conundrum of weak genetic and environmental effects, exceptional longevity is beginning to yield genetic findings. Numerous lower organism and mammalian models demonstrate genetic mutations that increase life-span markedly. These variations, some of them evolutionarily conserved, inform us about biochemical pathways that significantly impact upon longevity. Centenarian studies have also proven useful as they are a cohort that, relative to younger age groups, lacks genotypes linked to age-related lethal diseases and premature mortality.

Author(s): 
Perls, Thomas
Kunkel, Louis
Puca, Annibale
Publication Title: 
Pharmacogenomics

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.

Author(s): 
Perls, Thomas
Puca, Annibale
Publication Title: 
Experimental Gerontology

Centenarians exist at the extreme of life expectancy and are rare. A number of pedigree and molecular genetic studies indicate that a significant component of exceptional longevity is genetically influenced. Furthermore, the recent discovery of a genetic locus on chromosome 4 indicates the powerful potential of studying centenarians for genetic factors that significantly modulate aging and susceptibility to age-related diseases. These studies include siblings and children of centenarians.

Author(s): 
Perls, Thomas
Terry, Dellara
Publication Title: 
Journal of the American Geriatrics Society

OBJECTIVES: To assess the cause of death for centenarians' offspring and controls. DESIGN: Cross-sectional study. SETTING: Community-based, nationwide sample. PARTICIPANTS: Family pedigree information was collected on 295 offspring of centenarians (from 106 families with a parent already enrolled in the nationwide New England Centenarian Study) and on 276 controls (from 82 control families) from 1997 to 2000. Controls were individuals whose parents were born in the same year as the centenarians but at least one of whom died at the average life expectancy.

Author(s): 
Terry, Dellara F.
Wilcox, Marsha A.
McCormick, Maegan A.
Pennington, JaeMi Y.
Schoenhofen, Emily A.
Andersen, Stacy L.
Perls, Thomas T.
Publication Title: 
European journal of human genetics: EJHG

We conducted a sib pair study in very old subjects for the purpose of mapping longevity loci. In the present analysis, we explore whether our recruitment strategy has resulted in a population enriched for a heritable component for exceptional longevity. Our study includes families with at least two long-living siblings (men aged 89 years or above; women aged 91 years or above). Data were collected on date of birth and, if applicable, date of death of parents, brothers and sisters, offspring, and spouses of the long-living participants.

Author(s): 
Schoenmaker, Manja
de Craen, Anton J. M.
de Meijer, Paul H. E. M.
Beekman, Marian
Blauw, Gerard J.
Slagboom, P. Eline
Westendorp, Rudi G. J.
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.

Author(s): 
Willcox, Bradley J.
Willcox, D. Craig
He, Qimei
Curb, J. David
Suzuki, Makoto
Publication Title: 
Journal of the American Geriatrics Society

OBJECTIVES: To assess whether familial longevity can be attributed to sustained hematopoietic capacity. DESIGN: Prospective follow-up study of two independent population-based cohorts. SETTING: The Leiden Longevity Study and the Leiden 85-plus Study. PARTICIPANTS: From the Leiden Longevity Study, 1,001 nonagenarians with familial longevity were included. As age-matched controls, 260 nonagenarians without familial longevity were used from the Leiden 85-plus Study. MEASUREMENTS: Hemoglobin, leukocytes, and thrombocytes were measured for all subjects with and without familial longevity.

Author(s): 
Willems, Jorien M.
Trompet, Stella
Eline Slagboom, P.
de Craen, Anton J. M.
Westendorp, Rudi G. J.
Publication Title: 
The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences

The single nucleotide polymorphism, rs2866164, in the MTP gene, has been associated with human longevity but has not been validated by subsequent longevity studies. Using our population of Ashkenazi Jews, we find that the MTP CC genotype is significantly overrepresented in centenarians and their offspring, as compared with controls (p < .05). However, when we examined MTP CC genotype frequency pattern with aging, we observed a monotonic decline between ages 55-85 years followed by a dramatic enrichment after age 90 years, forming a U-shape pattern (p < .05).

Author(s): 
Huffman, Derek M.
Deelen, Joris
Ye, Kenny
Bergman, Aviv
Slagboom, Eline P.
Barzilai, Nir
Atzmon, Gil
Publication Title: 
PLoS biology

An increasing number of genes required for mitochondrial biogenesis, dynamics, or function have been found to be mutated in metabolic disorders and neurological diseases such as Leigh Syndrome. In a forward genetic screen to identify genes required for neuronal function and survival in Drosophila photoreceptor neurons, we have identified mutations in the mitochondrial methionyl-tRNA synthetase, Aats-met, the homologue of human MARS2. The fly mutants exhibit age-dependent degeneration of photoreceptors, shortened lifespan, and reduced cell proliferation in epithelial tissues.

Author(s): 
Bayat, Vafa
Thiffault, Isabelle
Jaiswal, Manish
TÈtreault, Martine
Donti, Taraka
Sasarman, Florin
Bernard, GeneviËve
Demers-Lamarche, Julie
Dicaire, Marie-JosÈe
Mathieu, Jean
Vanasse, Michel
Bouchard, Jean-Pierre
Rioux, Marie-France
Lourenco, Charles M.
Li, Zhihong
Haueter, Claire
Shoubridge, Eric A.
Graham, Brett H.
Brais, Bernard
Bellen, Hugo J.
Publication Title: 
Proceedings of the National Academy of Sciences of the United States of America

A gradual loss of telomeric repeat sequences with aging previously has been noted in normal adult tissues, and this process has been implicated in cell senescence. No data exist that address the rate of telomere shortening in normal human cells within families or early in life. To address these questions, we measured telomere lengths in peripheral blood leukocytes (PBLs) from 75 members of 12 families and in a group of unrelated healthy children who were 5-48 months old. Here we report the surprising observation that rates of telomere attrition vary markedly at different ages.

Author(s): 
Frenck, R. W.
Blackburn, E. H.
Shannon, K. M.

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